[Exploration and prospect of the whole course management model of osteoporosis].

Osteoporosis is a chronic progressive bone disease whose prevalence has increased significantly in China. Fragility fractures caused by osteoporosis pose a heavy burden on patients and their families. Therefore, early and efficient whole course management of osteoporosis is imperative. However, there are great challenges currently in the whole course management of osteoporosis, including lack of disease awareness, low rates of diagnosis and treatment, as well as poor patient compliance. As there is no consensus on the whole course management path to follow in clinical practice, this review analyzes the key points of whole course management of osteoporosis, such as the risk identification of fragility fracture, diagnosis and differential diagnosis, selection of initial treatment drugs, sequential or combined treatment and evaluation of treatment response etc. Based on the current management modes, including fracture liaison service, this review explores the whole course management path of osteoporosis which is suitable for China, including the whole course management ideas and implementation steps, establishing a platform to connect hospitals, communities, and families by application of information technology, developing an innovative system and mechanism indicates that the general practitioner will be responsible for clinical management and follow-up under instruction of clinical osteoporosis specialists, providing the community liaison service, organizing patient education activities such as bone health clubs, ultimately achieving a closed-loop communication among osteoporosis specialist, general practitioner, and patient, so that patients can benefit from it.

[Analysis of factors associated with proximal junctional kyphosis after surgery for Lenke type 5 adolescent idiopathic scoliosis].

Objective: To investigate the risk factors associated with the development of proximal junctional kyphosis (PJK) after posterior spinal fusion for in children with Lenke type 5 adolescent idiopathic scoliosis (AIS). Methods: It was a retrospective case-control study that included medical records of 98 children with Lenke type 5 AIS who underwent posterior orthopedic surgery under general anesthesia at the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2013 to December 2018. There were 23 males and 75 females with a mean age of (14.5±2.2) years (10-18 years). Patients were divided into PJK and non-PJK groups according to whether the posterior junctional angle (PJA) was greater than 10° and increased for more than 10° from the preoperative period at the the last follow-up. Univariate analysis was used to analyze the correlation of general data of the children with occurrence of PJK after the operation. Multivariate logistic regression analysis was used to analyze the risk factors of postoperative PJK. Results: There were 35 cases in the PJK group and 63 cases in the non-PJK group. The PJK and non-PJK groups were followed up for (35.6±7.3) months and (36.4±7.5) months, respectively, and the difference was not statistically significant (P=0.637). There was no statistically significant difference between the two groups in general data such as gender, age, and body mass index (all P>0.05), while there were statistically significant differences between the two groups in upper instrumented vertebrea (UIV) location and junctional area posterior ligamentous complex (PLC) injury (all P<0.05). The results of univariate analysis showed that UIV location at T10-T12, junctional area PLC injury, preoperative coronal thoracic curve (TC), preoperative and final follow-up PJA, and preoperative and final follow-up pelvic incidence-lumbarlordosis (PI-LL) were correlated with postoperative PJK (OR=2.50, 5.37, 0.92, 1.12, 1.32, 1.06, 3.35, all P<0.05). Multifactorial logistic regression analysis showed that UIV located at T10-T12 (OR=2.346, 95%CI: 1.582-3.481, P=0.001), junctional area PLC injury (OR=5.112, 95%CI: 1.283-20.418, P=0.023) and last follow-up PI-LL (OR=1.826, 95%CI: 1.558-24.745, P=0.012) were risk factors for the occurrence of postoperative PJK in children with Lenke type 5 AIS. Conclusions: Postoperative UIV fixation to the thoracolumbar segment, PLC injury in the junctional area and excessive postoperative PI-LL in children with Lenke type 5 AIS may be the risk factors for the occurrence of PJK after the operation. It is suggested that avoidance of UIV selection to the thoracolumbar segment, intraoperative protection of the PLC located near the UIV and restoration of a good PI-LL relationship may reduce the incidence of PJK.

[The development of artificial cervical disc replacement from the perspective of orthopedic bionic therapy].

The modern surgical treatment of cervical degenerative disc disease can be traced back to the advent of anterior cervical decompression and fusion.With the emergence of fusion-related complications,different scholars have promoted the gradual transformation of cervical degenerative disc diseases from "fusion fixation" to "non-fusion reconstruction" through in-depth fusion with materials science,engineering mechanics and other disciplines.The innovation of this treatment concept is consistent with the original intention of "structural remodeling,functional reconstruction,maximum repair and reconstruction of the morphology and function of skeletal muscle system" in orthopedic bionic treatment,which is essentially in line with the "bionic alternative therapy" in orthopedic bionic therapy.This paper focuses on the surgical treatment of cervical degenerative disc diseases,reviews the development history of artificial cervical disc replacement,analyzes the evolution from orthopedic biomimetic therapy,and explores a new direction for the design of artificial cervical disc prostheses and the treatment of cervical degenerative disc diseases in the future.

[Early efficacy of three dimensional printed anatomical biomimetic cervical artificial disc replacement in the treatment of cervical degenerative diseases].

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C3－4 level in 2 cases, C4－5 level in 5 cases, C5－6 level in 9 cases, and C6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.

[Clinical observation of single-segment cervical adjacent segment disease treated with artificial cervical disc replacement].

Objective: To investigate the clinical outcomes and radiographic results of artificial cervical disc replacement (ACDR) for cervical adjacent segment disease (ASD). Methods: The clinical data of 28 patients with single-segment cervical ASD treated with ACDR in Xi 'an Honghui Hospital from December 2013 to July 2016 were retrospectively analyzed. There were 19 males and 9 females with a mean age of (46±7) years (36-63 years). Preoperative, postoperative 1 month and postoperative 24 months of clinical and radiographic outcomes were recorded and compared. The clinical outcome mainly includes Japanese orthopedic association (JOA), Neck Disability Index (NDI%), Odom score and complications. Imaging assessment mainly included range of motion (ROM) of cervical spine, surgical segment ROM, Cobb angle of surgical segment, degree of adjacent disc degeneration, heterotopic ossification, and prosthesis related image parameters. Results: In terms of clinical outcome, the average JOA score was 12.7±1.5 before surgery, 14.0±1.0 one month after surgery, 15.8±0.9 24 months after surgery, and the improvement rate of JOA was 75%±19%. The mean NDI% was 27.0%±2.8% before surgery, 20.5%±1.6% one month after surgery, and 15.3%±2.8% 24 months after surgery; the difference before and after treatment was statistically significant (F=159.101, P<0.01). Twenty patients were classified with excellent Odom score and 8 patients with good Odom score at the final follow-up. The total ROM of cervical spine, operation segment ROM, operation segment Cobb angle were all improved significantly after the operation (F=4.633, 6.063, 26.952, all P<0.05). There was a statistical difference in Miyazaki classification between adjacent discs above ACDR and below the fusion segment 24 months after surgery (µ(c)=2.12, P=0.034). The incidence of heterotopic ossification was 14.3%. The results of displacement degree of prosthesis were as follow: coronal plane (0.30±0.11) mm, sagittal plane (0.28±0.10) mm; subsidence of the prosthesis: (0.27±0.09) mm. No prosthesis loosening was observed. Conclusions: The clinical outcome of revision of cervical ASD by ACDR is satisfactory. The risk of intervertebral disc degeneration in adjacent segments is significantly lower than that of ACDF due to the presence of certain motor function postoperatively.

Wharton's Jelly-derived mesenchymal stem cells suppress apoptosis of nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway.

OBJECTIVE: Aberrant apoptosis of nucleus pulposus cells (NPCs) is one of the most remarkable pathological changes in intervertebral disc degeneration (IDD) development. Albeit the advances in the application of stem cell-based therapy in IDD treatment, the molecular mechanisms underlying the anti-apoptotic actions of mesenchymal stem cell (MSC) remain poorly elucidated. PATIENTS AND METHODS: The expression patterns of apoptosis-related proteins and Wnt/ß-catenin-related genes in NP samples isolated from patients with mild or severe IDD were compared by performing immunoblot assay and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. NPCs were in vitro treated with compression to induce apoptosis and then co-cultured with Wharton's Jelly-derived MSCs without direct interaction. After that, flow cytometry was carried out to detect the apoptosis rate of NPCs and the activity of Wnt/ß-catenin pathway was determined. DKK-1 was used to inhibit Wnt signaling, in prior to evaluation of the effects of WJ-MSCs on apoptosis within the co-cultured NPCs. RESULTS: Compared to the mild IDD group, there was a significant increase in the expression of Caspase-3 and Bax in the NP tissues from severe IDD patients, whereas Bcl-2 displayed an opposite result. In addition, the expression of Wnt 3a, Wnt 5a, Wnt 10a, GSK-3ß, cyclinD1 and ß-catenin was notably augmented in parallel with IDD progression. After compression treatment, the proportion of apoptotic NPCs was increased, which was then dramatically reversed by WJ-MSCs co-culture. Likewise, WJ-MSCs suppressed compression-induced Wnt-related gene expression and blocking Wnt/ß-catenin pathway using DKK-1 enhanced the anti-apoptotic impacts of WJ-MSCs. In the presence of DKK-1, there was no significant difference between NPCs co-cultured with WJ-MSCs and those cells cultured alone. CONCLUSIONS: WJ-MSCs attenuate the compression-induced apoptosis in NPCs and inhibit the activation of Wnt/ß-catenin signaling. Blocking Wnt/ß-catenin pathway further facilitates the actions of WJ-MSCs in anti-apoptosis, indicating that Wnt/ß-catenin signaling plays a crucial role in this process and may function as a potential therapeutic target for IDD treatment.

[Clinical effects of free thinned deep inferior epigastric artery perforator flap in repairing extensive soft tissue defects in extremities].

Objective: To explore the feasibility and clinical effects of using free thinned deep inferior epigastric artery perforator flap to repair extensive soft tissue defects in extremities. Methods: From April 2010 to January 2014, 12 patients with extensive soft tissue defect in extremities after trauma, including 10 males and 2 females, aged 21 to 48 years, 6 patients with defect in the back of wrist and 6 patients with defect in ankle were admitted to the Department of Bone Microsurgery of Xi'an Honghui hospital. After debridement, the size of soft tissue defect ranged from 15.0 cm×4.5 cm to 28.0 cm×11.0 cm. The free thinned deep inferior epigastric artery perforator flap was designed, cut and transferred for reconstruction, with size of 15.0 cm×5.0 cm to 29.0 cm×12.0 cm. The flap thickness ranged from 4.0 to 6.5 cm before defatting, and was 0.6 to 0.9 cm after defatting. All the donor sites of flaps were closed directly by suturing. The flap survival and the appearance and function of flap and donor site were observed during follow-up. Results: All the flaps survived smoothly after surgery. During follow-up of 10 to 42 months, the flaps showed no bloat in appearance, no further flap revision or defatting procedures were required, the distance of static 2-point discrimination was 11 to 17 mm (14.5 mm on average). The abdominal function of patients was not affected, and no postoperative abdomen hernia or ulceration was noted. Conclusions: The free thinned deep inferior epigastric artery perforator flap is thin and suitable for repairing extensive soft tissue defects in extremities with very good outcomes.

Suberoylanilide hydroxamic acid attenuates epidural fibrosis via inhibiting myofibroblast differentiation and increasing fibroblast apoptosis.

OBJECTIVE: Epidural fibrosis represents a fatal stage of failed back surgery syndrome (FBSS) of known and idiopathic etiology, but no valid therapy is presently available. Previous evidence demonstrated that suberoylanilide hydroxamic acid (SAHA), a histone deacetylases inhibitor, has antifibrotic and anti-inflammatory potential. Current studies have proved that SAHA inhibits myofibroblast differentiation and increases fibroblast apoptosis to attenuate epidural fibrosis. The purpose of this study was to investigate the effect and mechanism of SAHA on repressing epidural fibrosis. PATIENTS AND METHODS: First, the levels of acetylation of histone and α-tubulin in adult human fibroblasts (AHF) and human epidural fibroblasts (HEF) were analyzed following SAHA and transforming growth factor-ß(TGF-ß) treatment. Then, mRNA and protein obtained from human fibroblasts following TGF-ß activation and SAHA treatment in vitro culture were used to test the influence of SAHA on the activation and apoptosis of fibroblasts, so as to further explore the related mechanism of SAHA. Then, a laminectomy model was established in rats to observe the therapeutic effect of SAHA on epidural scar tissue. RESULTS: The present research proved that the increases of HDAC 3 and α-tubulin were observed in AHF and HEF after TGF-ß administration, but SAHA decreased HDAC 3 and α-tubulin expressions. In addition, cell study demonstrated that SAHA inhibited fibroblast activation via decreasing TGF-ß function and accelerated apoptosis by promoting cleaved-caspase-3. In the epidural fibrosis model, it was found that SAHA weakened scar hyperplasia and collagen deposition, and effectively inhibited the process of epidural fibrosis. CONCLUSIONS: These results indicated that SAHA inhibited HDAC 3 expression, decreased TGF-ß effect, and enhanced caspase-3 in fibroblasts, leading reduction of myofibroblast activation and apoptosis elevation. Hence, SAHA ameliorated epidural fibrosis development.

MiR-30a-3p promotes ovariectomy-induced osteoporosis in rats via targeting SFRP1.

OBJECTIVE: To explore the effect of miR-30a-3p on osteoporosis in rats after ovariectomy. MATERIALS AND METHODS: The ovariectomized (OVX) rat model was established to mimic postmenopausal osteoporosis. The primary bone marrow mesenchymal stem cells (BMMSCs) isolated from female rats were transfected with mimic or inhibitor. Real Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were used to examine the expressions of miR-30a-3p and osteoporosis-related proteins. The bone mineral density (BMD) was detected via micro-Computed Tomography (CT) and the bone histomorphometry was performed. Luciferase assay was also performed to confirm whether SFRP1 is a target of miR-30a-3p. RESULTS: According to micro CT, BMD significantly declined in OVX group. MiR-30a-3p and SFRP1 were negatively correlated after ovariectomy. SFRP1 was acknowledged as a target of miR-30a-3p. Besides, the miR-30a-3p inhibitor promoted osteogenic differentiation in vitro and bone formation in vivo. CONCLUSIONS: MiR-30a-3p inhibitor promotes bone formation through decreasing SFRP1 expression and miR-30a-3p may be a potential novel molecular target in the treatment of osteoporosis.

The nuclear hormone receptor E75A regulates vitellogenin gene (Al-Vg) expression in the mirid bug Apolygus lucorum.

Apolygus lucorum is the predominant pest of Bacillus thuringiensis (Bt) cotton in China. 20-hydroxyecdysone (20E) plays a key role in the reproduction of this insect. To better understand the mechanism underlying 20E-regulated reproduction, the nuclear hormone receptor E75 isoform-A of Ap. lucorum (Al-E75A) was cloned and its expression analysed. A 2241-bp sequence of Al-E75A cDNA encoded an open reading frame of a polypeptide with a predicted molecular mass of 69.04 kDa. Al-E75A mRNA was detected in female adult stages of Ap. lucorum with peak expression in 7-day-old animals. Al-E75A was also expressed in several tissues, particularly in the fat body and ovary. A 3.2 kb Al-E75A mRNA was detected in all tissues by Northern blot. The fecundity and longevity were significantly decreased in female adults treated with Al-E75A small interfering RNA. The rates of egg incubation rates were considerably lower in the RNA interference-treated animals compared to the untreated controls. In order to investigate the molecular mechanism underlying the effects described above, vitellogenin (Al-Vg) was selected for further investigation. The expression pattern of Al-Vg was similar to that of Al-E75A and was up-regulated by 20E. After knockdown of Al-E75A, the expression profile of Al-Vg and the protein levels were down-regulated. These findings suggest that Al-E75A plays a crucial role in the regulation of Al-Vg expression in Ap. lucorum.

Tumour-associated antigens and their anti-cancer applications.

So far, a number of tumour-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, carcino-embryonic antigen and others have been identified in a variety of malignant tumours. Differences in the expression levels of TAAs in cancers compared with normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers or exciting targets in cancer treatment. Here, we systematically list the current representative TAAs to shed some light on current approaches and challenges for their anti-cancer application in cancer therapy. In this review, we discuss the ongoing pre-clinical studies and clinical development of TAAs in human cancers, and the potential application of these TAAs in the diagnosis and prognosis for cancer treatment.

Accuracy of CT-guided biopsies in 158 patients with thoracic spinal lesions.

BACKGROUND: Inconsistent accuracies of CT-guided thoracic spinal biopsies have been reported in previous studies. PURPOSE: To determine the accuracy of CT-guided thoracic spinal biopsy, to compare the results with those previously reported, and to determine if there are any factors that influence the accuracy of CT-guided thoracic spinal biopsy. MATERIAL AND METHODS: In total, 158 consecutive CT-guided percutaneous thoracic spine procedures (performed at the Department of Spinal Surgery, Xi'an Red Cross Hospital between April 2000 and July 2010) were reviewed. The 158 lesions were categorized by location and radiographic features. Pathological and clinical follow-up were used to determine accuracy. RESULTS: The diagnostic accuracy of CT-guided thoracic spinal biopsy was 90.5% overall. Biopsy of metastatic bone disease (98.2%) was significantly more accurate than biopsies of primary tumors (80.9%) and of hematological malignancies (47.0%) (P < 0.05 and P < 0.005, respectively). The diagnostic accuracy of CT-guided thoracic spinal biopsy was significantly higher for the lower thoracic spine (97.6%) than for the middle (90.0%) or upper thoracic spine (80.4%) (P < 0.05 and P < 0.025, respectively). The diagnostic accuracy was significantly higher for lytic lesions (96.4%) than for sclerotic lesions (81.3%) (P < 0.010). The accuracy of biopsies performed using the transpedicular approach (91.0%) was not significantly different from that of biopsies performed using posterolateral approaches (91.5%) (0.25 < P < 0.5). CONCLUSION: Percutaneous CT-guided thoracic spinal biopsy is a viable alternative to open surgical biopsy. The diagnostic accuracy was not affected by any of the variables except for lesion level, histology, and radiographic features.