Widespread in situ follicular neoplasia in patients who subsequently developed follicular lymphoma.

In situ follicular neoplasia (ISFN) is usually an occasional incidental finding in lymph nodes by BCL2 immunohistochemistry, and its true scale is unknown. We have identified six cases of follicular lymphoma (FL) with a history of solid neoplasm 4-16 years ago, from which ISFN was identified widely in the surgically cleared lymph nodes (LNs). Using clone-specific PCR and BaseScope in situ hybridisation with primers or probes specific to the VDJ or BCL2-IGHJ junction sequence, we confirmed the clonal identity among different ISFNs and overt-FL in each of the four cases successfully investigated. Mutation analyses of overt-FL by targeted next-generation sequencing identified multiple potential pathogenic changes involving CREBBP, EZH2, KMT2D, TNFRS14, and STAT6. Further investigations of these mutations in paired ISFNs using Fluidigm PCR and Illumina sequencing showed the presence of the FL-associated mutations in early lesions for two of the six cases investigated (CREBBP and KMT2D in one case and STAT6 in the other), with one case displaying stepwise accumulation of its observed mutations. Remarkably, there were considerable divergences in BCL2 variants among different ISFN-involved lymph nodes in all four cases successfully investigated, indicating ongoing intraclonal diversification by somatic hypermutation machinery. Our findings demonstrate widespread distribution of ISFN lesions, further implicating their dynamic nature with the neoplastic cells undergoing active trafficking and clonal evolution. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Effectiveness of abduction brace versus simple sling rehabilitation following rotator cuff repair: systematic review and meta-analyses.

BACKGROUND: To date, no conclusions have been reached regarding the type of brace worn after arthroscopic rotator cuff repair. To this end, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted. METHODS: According to the updated guidelines of the Preferred Reporting Items of Systematic Review and Meta-Analysis, all related literature in PubMed, Embase, and Cochrane Central Register of Controlled Trials, from their establishment to March 1, 2022, were searched systematically. Outcome measures included the Constant score, Western Ontario Rotator Cuff (WORC) index, visual analog scale (VAS) score, shoulder joint range of motion (ROM), and failure events of rotator cuff healing. The Cochrane risk of bias tool was used to evaluate the quality of RCT. RESULTS: Two independent reviewers (Chen, Wu) reviewed 275 articles, of which only five met the inclusion criteria, and four were included in the meta-analysis, with a total of 302 patients. The overall risk of bias was high in two RCTs, unclear in one, and low in two. Considering the clinical outcomes, the Constant score (P = .08 mean deviation [MD], 3.06; 95% confidence interval [CI], -0.42 to 6.53), WORC (P = .23; MD, 3.32; 95%CI, -2.15 to 8.79), VAS score (P = .09; MD -1.27; 95%CI, -2.75 to 0.21), ROM (P = .1; MD, 4.75; 95%CI, -0.98 to 10.48), and failure events of rotator cuff healing (P = .78; odds ratio [OR], 0.86; 95%CI, 0.32 to 2.37) did not significantly differ between the abduction brace and simple sling after arthroscopic rotator cuff repair. CONCLUSION: The findings of this systematic review and meta-analysis suggest that wearing abduction braces after rotator cuff repair neither improved the Constant score, VAS, and WORC scores, and ROM of the shoulder joint, nor did it reduce the risk of re-tearing. Therefore, a simple sling may be a better option in terms of cost effectiveness. It is expected that studies with larger and more homogeneous samples will help verify our results.

Prevalence and radiographic features of atlantoaxial dislocation in adult patients with Kashin-Beck disease.

PURPOSE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy affecting the epiphyseal growth plate of multiple joints in young and adolescent patients. Previous studies have focused on the visible deformed extremities instead of the spinal radiological features, especially the atlantoaxial joint. The aim of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in adult patients with KBD. METHODS: This study was conducted on KBD patients in three typical endemic counties between October 2017 and November 2019. The patients were evaluated by collecting basic information, clinical signs and symptoms. They underwent dynamic cervical radiography, by which AAD was diagnosed. For those patients with confirmed or suspected AAD, computed tomography (CT) imaging was performed to observe the odontoid morphology and degenerative changes in the lateral atlantoaxial joints. Radiographic evaluations were reviewed to determine the prevalence and features of AAD. RESULTS: A total of 39 (14.6%) of 267 KBD patients were diagnosed with AAD. Compared with the non-AAD patients, the detection rate of AAD was associated with a longer disease duration and stage and was not associated with age, sex or BMI. Thirty-two patients had symptoms at the neck or neurological manifestations, while seven had no symptoms. There were three types of morphologies of the odontoid process in AAD patients: separating in 19 cases, hypoplastic in 15 cases and intact in five cases. Anterior dislocation was noted in 29 cases, and posterior dislocation was noted in ten cases. Thirty-four cases were reducible, and five were irreducible. The lateral atlantoaxial joints had different severities of degenerative changes in 17 cases. CONCLUSIONS: This study revealed that the prevalence of AAD was 14.6% in adult KBD patients. The radiographic features of AAD include manifestations of odontoid dysplasia and chronic degenerative changes in atlantoaxial joints. KBD patients with severe stages and longer disease duration were more vulnerable to the occurrence of AAD. We postulate that this atlantoaxial anomaly might originate from chondronecrosis of the epiphyseal growth plate of the odontoid process in young and adolescent individuals. This study may provide a clinical reference to help clinicians screen, prevent and treat AAD in adult patients with KBD.

RPL38 knockdown inhibits the inflammation and apoptosis in chondrocytes through regulating METTL3-mediated SOCS2 m6A modification in osteoarthritis.

BACKGROUND: Ribosomal protein L38 (RPL38) was found upregulated in osteoarthritic peripheral blood mononuclear cells, however, its role in progression of osteoarthritis has not been characterized. METHODS: The protein levels of RPL38 and SOCS2 in cartilage tissues from OA patients and controls were detected with Western blotting. IL-1ß was used to stimulate primary chondrocytes to establish an OA cell model, and RPL38 siRNA (si-RPL38) was transfected into chondrocytes to investigate the effect of RPL38 knockdown on cell viability, apoptosis, inflammatory factor secretion and extracellular matrix degradation. Then, the mechanism that RPL38 regulate the SOCS2 expression and SOCS2-induced chondrocyte dysfunction was explored. The methyltransferase-like 3 (METTL3)-mediated m6A modification of SOCS2 mRNA was confirmed, and the interaction of RPL38 and METTL3 was verified. Moreover, the effects of SOCS2 overexpression on IL-1ß-induced chondrocyte dysfunction and SOCS2 knockdown on the restoration of chondrocyte function by siRPL38 were investigated. Finally, RPL38 was knocked down in vivo and its role in OA progression was validated. RESULTS: RPL38 was upregulated and SOCS2 was downregulated in OA cartilages. RPL38 knockdown or SOCS2 overexpression either attenuated IL-1ß-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation. RPL38 directly interacted with METTL3 and it inhibited SOCS2 expression through METTL3-mediated m6A modification. SOCS2 knockdown activated the JAK2/STAT3 proinflammatory pathway and reversed the effects of RPL38 knockdown on IL-1ß-induced chondrocyte apoptosis, inflammation and ECM degradation. RPL38 knockdown alleviated cartilage tissue damage and ECM degradation in OA mice. CONCLUSION: RPL38 knockdown inhibited osteoarthritic chondrocyte dysfunction and alleviated OA progression through promoting METTL3-m6A-mediated SOCS2 expression.

Inhibiting silence information regulator 2 and glutaminase in the amygdala can improve social behavior in autistic rats.

OBJECTIVE: To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats. METHODS: Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 -/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed. RESULTS: Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 -/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01). CONCLUSIONS: The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.

HSP70 alleviates spinal cord injury by activating the NF-kB pathway.

OBJECTIVES: Spinal cord injury (SCI) is an acute traumatic lesion of neurons in the spinal cord which has a high prevalence in the world, and has no effective surgical treatment. HSP70 is a molecular chaperone protein, serves a protective role in several different models of nervous system injury. The aim of the present study was to investigate the anti-inflammatory role of HSP70 in spinal cord injury and explore its mechanism. METHODS: In vivo and in vitro models were constructed to mimic SCI. The Basso Mouse Scale (BMS) was applied to assess SCI degrees of the mouse model. Immunofluorescence (IF) was used for visualizing HSP70 and Iba1 in the spinal cord. Western blot assay was employed to quantify HSP70 and p65, and ELISA was for IL-1ß and TNF-α. RESULTS: The results showed that HSP70 expression decreased after SCI. HSP70 and Iba1 showed a decrease of co-localization in SCI mice. Further studies revealed that p65 was upregulated during the process of SCI. Overexpression of HSP70 inhibited the expression of p65 both in vitro and in vivo, and promoted the recovery of SCI mice. CONCLUSIONS: HSP70 was involved in the pathological process of spinal cord injury, HSP70 alleviated the spinal cord injury via inhibiting NF-κB signaling pathway.

S100-ß aggravates spinal cord injury via activation of M1 macrophage phenotype.

OBJECTIVES: S100-ß has been identified as a sensitive biomarker in central nervous system injuries. However, the functions and mechanisms of S100-ß are unknown in spinal cord injury. METHODS: Spinal cord injury (SCI) mouse model was generated by surgical operation, microglia activation model was established by inducing BV-2 cells with LPS. The SCI model was evaluated by Basso-Beattie-Bresnahan (BBB) behavioral score, HE staining, and Nissl staining. The expression level of S100-ß was detected by qRT-PCR, western blot, and immunofluorescence. qRT-PCR and western blot were used to detect the expression of iNOS and CD16. Pro-inflammatory cytokines TNF-α and IL-1ß levels were detected by qRT-PCR and ELISA. RESULTS: The expression of IL-1ß, TNF-α, iNOS, and CD16 increased at 3rd day after SCI. In BV2 microglia, LPS treatment promoted the expression of S100-ß, IL-1ß, TNF-α, iNOS, and CD16. Knockdown of S100-ß reduced the expression of iNOS stimulated by LPS. Over-expression of S100-ß increased IL-1ß and TNF-α, and S100-ß inhibition suppressed IL-1ß and TNF-α. In SCI mice, knockdown of S100-ß attenuated the spinal cord injury and inhibited the expression of iNOS, IL-1ß, and TNF-α. CONCLUSIONS: Down-regulation of S100-ß could inhibit the pathogenesis of SCI and inhibit the activation of M1 macrophages. S100-ß may be a useful diagnostic biomarker or therapeutic target for SCI.

Long noncoding RNA PWRN1 is lowly expressed in osteosarcoma and modulates cancer proliferation and migration by targeting hsa-miR-214-5p.

BACKGROUND: We examined the expression pattern, clinical relevance, and molecular mechanisms of lncRNA PWRN1 in human osteosarcoma. METHODS: qPCR was used to measure PWRN1 expressions in cell lines and tumor samples osteosarcoma. The correlations between PWRN1 and cancer patients' clinicopathological properties and survival were examined. PWRN1 was ectopically overexpressed in MG-63 and 143B cells to assess its function on cancer cell proliferation, cisplatin chemoresistance, and in vivo xenotransplant growth. The ceRNA candidate of PWRN1, miR-214-5p was examined in osteosarcoma cells. In addition, miR-214-5p and PWRN1 were double-overexpressed in osteosarcoma cells to investigate the regulatory role of epigenetic axis PWRN1/miR-214-5p in osteosarcoma. RESULTS: We found that PWRN1 was downregulated in both osteosarcoma cells and human tumors. PWRN1 downregulation was correlated with advanced stage, metastasis, and low survival rate in cancer patients. PWRN1 overexpression in osteosarcoma cells significantly inhibited their proliferation, cisplatin chemoresistance, and in vivo growth. In addition, we demonstrated that PWRN1 directly bound miR-214-5p and suppressed its expression in osteosarcoma cells. Furthermore, we showed that miR-214-5p overexpression reversed the anti-cancer effects of PWRN1 on osteosarcoma cell proliferation and cisplatin chemoresistance. CONCLUSION: Our data provide new insights into the epigenetic axis of PWRN1/miR-214-5p in regulating osteosarcoma progression and chemoresistance. PWRN1 may also be a biomarker to predicting cancer patients' poor prognosis and novel pharmaceutical targets for personalized medicine.

Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy.

Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.

Let-7b-5p regulates proliferation and apoptosis in multiple myeloma by targeting IGF1R.

Multiple myeloma (MM) is the most common cause of death from hematological malignancy worldwide, and recent studies have revealed that let-7b-5p can play an inhibitory role in tumorigenesis. However, the role of let-7b-5p in MM still remains unclear. The aim of this study was to elucidate the molecular mechanisms by which let-7b-5p acts as a tumor suppressor in MM. Here, quantitative real-time polymerase chain reaction results showed that the expression of let-7b-5p was remarkably reduced in MM tissues and MM cell lines (RPMI-8226 and U266 cells). Furthermore, over-expression of let-7b-5p significantly suppressed RPMI-8226 cell proliferation and induced S/G2 cell cycle arrest and apoptosis. Luciferase reporter assay results demonstrated that insulin-like growth factor receptor 1 (IGF1R) was negatively regulated by let-7b-5p at the post-transcriptional level. The mRNA and protein levels of IGF1R in RPMI-8226 cells were down-regulated by let-7b-5p. Furthermore, the cell phenotype altered by let-7b-5p inhibitor can be rescued by IGF1R silencing (si-IGF1R). Taken together, our results demonstrated that let-7b-5p functions as a tumor suppressor in MM, suggesting that let-7b-5p may be a potential therapeutic target for MM.

A novel method to evaluate the transverse pedicle angles of the lower lumbar vertebrae using digital radiography.

To investigate a novel approach for establishing the transverse pedicle angle (TPA) of the lower lumbar spine using preoperative digital radiography (DR). Computed Tomography (CT) datasets of the lower lumbar were reconstructed using MIMICS 17.0 software and then imported into 3-matic software for surgical simulation and anatomical parameter measurement. A mathematical algorithm of TPA based on the Pythagorean theorem was established, and all obtained data were analyzed by SPSS software. The CT dataset from 66 samples was reconstructed as a digital model of the lower lumbar vertebrae (L3-L5), and the AP length/estimated lateral length for L3 between the right and left sides was statistically significant (P = 0.015, P = 0.005). The AP length of the right for L4 was smaller than that of the left after a paired t test was executed (P = 0.006). Both the width of the pedicle and the length of the pedicle (P2C1) were consistent with TPA (L3

Different radius of curvature at the talus trochlea from northern Chinese population measured using 3D model.

BACKGROUND: To analyze the curvature characteristics of the talus trochlea in people from northern China in different sex and age groups. METHODS: Computed tomography scanning data of talus from 61 specimens were collected and constructed as a three-dimensional model by Materialise's Interactive Medical Image Control System(MIMICS) software, anteromedial(AM), posteromedial(PM), anterolateral(AL), and posterolateral(PL) edge, anterior edge of medial trochlea, posterior edge of medial trochlea and anterior edge of lateral trochlea were defined according to the anatomical landmarks on trochlear surface. The curvature radii for different areas were measured using the fitting radius and measure module. RESULTS: There were significant differences among the talus curvatures in the six areas (F = 54.905, P = 0.000), and more trends in the analytical results were as follows: PM > PL > MP > AL > MA > AM. The average PL radius from specimens aged > 38 years old was larger than that from specimens aged < = 38 years (t=-2.303, P = 0.038). The talus curvature of the AM for males was significantly larger than that for females (t = 4.25, P = 0.000), and the curvature of the AL for males was larger than that for females (t = 2.629, P = 0.010). For observers aged < = 38 years, the AM curvature of the right talus in the male group was significantly larger than that in the female group (P < 0.01). In age < = 38years group, the MA curvature of right talus in male was significantly larger than in female group(P < 0.01), fitting radius of talus for male (21.90 ± 1.97 mm) was significantly greater than female of this(19.57 ± 1.26 mm)(t = 6.894, P = 000). The average radius of the talus in the male population was larger than that in the female population. CONCLUSION: There was no significant relationship between age and talus curvature for males and females. The radius of curvature in the posterior area was significantly larger than that in the anterior area. We recommend that this characteristic of the talus trochlea should be considered when designing the talus component in total ankle replacement (TAR).

Asymmetric warming reduces the strength of selection pressure of moderate grazing on reproductive phenology in alpine plants.

Both warming and grazing already affect the reproductive phenology of alpine plants. However, their effects have mostly been studied in isolation, and their interaction is still unclear. In this study, an asymmetric warming (average + 1.2 °C during daytime and + 1.7 °C during nighttime and + 1.5 °C during summer and + 2.0 °C during winter) with moderate grazing experiment was conducted for four years to determine their individual and interactive effects on the onsets and durations of reproductive phenophases for fifteen alpine plant species on the Qinghai-Tibetan Plateau. Individual warming and grazing simultaneously advanced the average start dates and ending dates of budding, flowering and fruiting by 5.3-6.2 days, and further resulted in smaller effects on their durations for most plant species. The interactions between warming and grazing on them varied with plant species and year, which advanced by average 12.1 days for all plant species. The effects of grazing on the temperature sensitivity of the start dates of reproductive phenophases (average by -8.5 days °C-1) were greater than that of warming alone (average by -3.4 days °C-1) and warming with grazing (average by -5.5 days °C-1) for most of the alpine plant species. There were significant effects of the previous phenological events on subsequent reproductive phenophases. Therefore, our results suggested that both warming and grazing advanced reproductive phenophases through altered soil temperature and soil moisture and carry-over effects of previous phenological events on subsequent phenological events. Warming reduced the temperature sensitivity of the start dates of reproductive phenophases to grazing, suggesting that it depressed strength of selection pressure of grazing on the onsets of reproductive phenology in alpine plants.

Health-related quality of life in patients with Kashin-Beck disease is lower than in those with osteoarthritis: a cross-sectional study.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire. METHODS: A total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects. RESULTS: The average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score. CONCLUSION: The QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.

Warming delays but grazing advances leaf senescence of five plant species in an alpine meadow.

Leaf senescence is the final stage in the life cycle of leaves and is critical to plants' fitness as well as to ecosystem carbon and nutrient cycling. To date, most understanding about the responses of leaf senescence to environmental changes has derived from research in forests, but the topic has been relatively neglected, especially under grazing conditions, in natural grasslands. We conducted a 3-year manipulative asymmetric warming with moderate grazing experiment to explore the responses of leaf senescence of five main species in an alpine meadow on the Qinghai-Tibetan Plateau. We found that warming prolonged leaf longevity through earlier leaf-out and later leaf senescence, and grazing prolonged it through a greater advance in leaf-out than first leaf coloration for all plants. Warming did not affect leaf nitrogen (N) content or N resorption efficiency (NRE), but grazing increased N content in coloring leaves for P. anserine and P. nivea and decreased NRE for K. humilis, P. anserine under no-warming, and for P. nivea under warming. The interactive effects of warming and grazing on leaf phenology and leaf traits depended on species identity and year. There were positive relationships between leaf-out and leaf senescence mainly derived from grazing, and positive relationships between NRE from old leaves and leaf senescence for three out of five plant species. Therefore, our results indicated that earlier leaf-out could result in earlier leaf senescence only under grazing, but depending on plant species. Delayed leaf coloring increased NRE from old leaves for some plant species measured under warming and grazing. Our results suggested that alpine plants may develop strategies to adapt to warming and grazing to assimilate more carbon through prolonged leaf longevity rather than increased NRE through earlier leaf coloring in the alpine meadow.

Long intergenic non-protein coding RNA 00707 regulates chondrocyte apoptosis and proliferation in osteoarthritis by serving as a sponge for microRNA-199-3p.

It is known that long intergenic non-protein coding RNA 00707 (LINC00707) promotes lipopolysaccharide (LPS)-injury and microRNA-199-3p (miR-199-3p) regulates chondrocyte proliferation and apoptosis. Both processes participate in osteoarthritis (OA). We predicted that LINC00707 and miR-199-3p may interact with each other. Therefore, LINC00707 and miR-199-3p may interact with each other to participate in OA. In this study, the expression of LINC00707 and miR-199-3p in both OA and normal articular cartilage tissues was analyzed using RT-qPCR. The subcellular location of LINC00707 and its direct interaction with miR-199-3p were explored by nuclear fractionation assay, RNA pull-down assay and Luciferase reporter assay, respectively. The role of LINC00707 and miR-199-3p in regulating the expression of each other was analyzed using an overexpression assay, followed by RT-qPCR. The role of LINC00707 and miR-199-3p in regulating OA chondrocyte proliferation and apoptosis was analyzed by BrdU assay and cell apoptosis assay, respectively. OA tissues exhibited increased expression of LINC00707 and decreased expression of miR-199-3p. LINC00707 directly interacted with miR-199-3p in cytoplasm. However, LINC00707 and miR-199-3p overexpression failed to affect each other's expression. LPS treatment increased LINC00707 expression and decreased miR-199-3p expression in OA chondrocyte. LINC00707 overexpression increased the apoptosis of OA chondrocytes induced by LPS and suppressed the proliferation of OA chondrocytes. Moreover, LINC00707 suppressed the role of miR-199-3p in enhancing cell proliferation and suppressing cell apoptosis. In conclusion, LINC00707 can be detected in cytoplasm and it may sponge miR-199-3p to regulate chondrocyte proliferation and apoptosis in OA.

Protective Effect of Extended Laminectomy on Spinal Cord Injury Induced by Spinal Shortening.

This study investigates the effect of extended laminectomy (EL) on spinal cord injury (SCI) caused by spinal shortening, and further, the timing and the optimal length of removal. Dogs received spinal column shortening at T13 segment, following which the control group underwent regular laminectomy while other groups underwent laminectomy with an additional 1-lamina length removed 6h after shortening ("1-lamina EL 6 h"), an extra 1.5-lamina length resected at 6 h or 12 h after shortening ("1.5-lamina EL 6 h" and "1.5-lamina EL 12 h"), and an extra 2-lamina length removed at 6 or 12 h after shortening ("2-lamina EL 6 h" and 2-lamina EL 12 h"), respectively. Somatosensory evoked potential (SSEP) and neurological function were recorded periodically; spinal cord blood flow (SCBF) and nerve cell apoptosis were detected. The results showed that resection of an additional 1-lamina length appeared inadequate to relieve the sharp kinking of the spinal cord, whereas the kinking disappeared with an additional 2-lamina length resection. The "1-lamina EL 6 h" and "1.5-lamina EL 12 h" groups showed no significant differences from the control in latency of SSEP, SCBF, hindlimb function and apoptosis. By contrast, significant recovery of SSEP, SCBF and hindlimb function as well as reduction of apoptosis were presented in other three groups. The "2-lamina EL 6 h" group, in particular, showed the most prominent recovery. In conclusion, an additional resection of two laminae at 6 h after shortening showed the best effect in alleviating SCI. Timely and adequately extended laminectomy could be a potential therapeutic strategy for SCI attributable to spinal shortening.

A Novel Method for Preoperative Positioning of Total Ankle Replacement Using 3D Digital Model.

OBJECTIVE: To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. METHODS: Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. RESULTS: The dataset of this study included 48 cases of the sub-data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3 , the mid-anterior distance was 1.72 ± 0.19 cm, the mid-posterior distance was 2.00 ± 0.19 cm, the ratio of mid-anterior to mid-posterior was 0.87, the mid-medial distance was 1.26 ± 0.17 cm, the mid-lateral distance was 1.19 ± 0.16 cm, and the ratio of mid-medial to mid-lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid-anterior distance was strongly negatively correlated with age, the mid-anterior distance and the amount of bone resection, the mid-medial distance and the amount of bone resection, the mid-lateral distance and the amount of bone resection, the mid-lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. CONCLUSION: The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.

An Imaging Measurement Study of Normal Knee Parameters in Southeast China.

BACKGROUND: Imaging measurement of distal femur and proximal tibia has been the hot point in the research of total knee arthroplasty and prosthesis development, which is an important treatment for patients with advanced knee joint disease. This study retrospectively investigated the digital imaging measurement of normal knee parameters in southeast China and evaluated their clinical value. METHODS: From February 2010 to May 2014, and in accordance with the inclusion criteria, a total of 677 knees (334 female knees and 343 male knees) were categorized into 3 age groups. Clinical and digital imaging data, including the distal Femoral Condyle Diameter (FCD), Tibial Plateau Diameter (TPD), the distance between the medial tibial plateau and fibular head (DPF), tibiofemoral valgus angle, distal femoral valgus angle, Proximal Tibia (PT) varus angle and the angle from femoral condyle to tibial perpendicular (FT), were measured by using AutoCAD 10.0 software. All measured variables were statistically analyzed by SPSS statistical software (version 18.0). RESULTS: Data are presented as the mean ± standard deviation. The normal female and male femoral condyle diameter was (7.69 ± 0.46) cm and (8.68 ± 0.55) cm, while the normal female and male tibial plateau diameter was (7.66 ± 0.46) cm and (8.60 ± 0.55) cm, respectively. The normal female and male DPF was (0.76 ± 0.36) cm and (0.79 ± 0.36) cm. For females and males, the tibiofemoral valgus angle and distal femoral valgus angle were (3.89 ± 2.20) ° and (3.29 ± 2.12) °, (9.03 ± 2.18) ° and (8.25 ± 2.20) °. As the two methods to measure tibial plateau varus angle, PT angle of normal female and male was (4.29 ± 1.86) ° and (4.84 ± 2.23) °, while the normal female and male FT angle was (5.34 ± 1.95) ° and (5.52 ± 2.07) °. Based on the data obtained, we found significant differences between the two genders in terms of the femoral condyle diameter and tibial plateau diameter in all age groups (P < 0.01). The DPF parameter showed an obvious difference between the young group and the middle-aged group (P < 0.05), and no significant difference was observed between the sides and genders (P > 0.05). The distal femoral valgus angle showed statistical differences between genders in the left side of the young group and middle-aged group (P < 0.05), while angle PT and FT showed no significant difference (P > 0.05). CONCLUSION: A large number of knee measurements was obtained, and a local knee database was developed in this study. Imaging measurement prior to total knee arthroplasty is clinically important for increasing the accuracy and long-term efficacy of total knee arthroplasty. These data can also provide useful information for knee surgery and sports medicine as well as prosthesis development.

DR4-Associated Death Receptor Signal Promotes Cartilage Damage in Patients With Kashin-Beck Disease.

Purpose. To explore the relationship between the death receptor (DR) and the pathological progression of Kashin-Beck disease (KBD). Design. KBD cartilage samples were collected from 15 patients diagnosed according to the "National Diagnostic Criteria of KBD" in China. In vitro monolayer chondrocytes were cultured in complete medium. Caspase-3 and caspase-8 activities in chondrocytes were analyzed using a kit. Nuclear morphology was observed by Hoechst 33258 staining, apoptosis was verified by flow cytometry analysis, and DR molecules were detected using Western blotting and quantitative real-time reverse transcription polymerase chain reaction analysis. Results. Early apoptotic rates of KBD and osteoarthritis (OA) chondrocytes were higher than those of normal control (NC) cells. Excessive apoptotic nuclei were observed in OA and KBD cells after Hoechst 33258 staining. Activities of both caspase-3 and caspase-8 were higher in KBD and OA cells than in NC cells. The average DR4 mRNA level in KBD cells was 3.301-fold higher than that in NC cells, Fas-associating protein with death domain (FADD) transcript level in KBD cells was 2.528-fold higher than that in NC cells. Western blot analyses showed that FAS, DR4, DR5, caspase-3, and FADD were upregulated in the KBD and OA groups compared with the NC group. High expression of caspase-8 in KBD compared with NC was verified, whereas cellular FLICE-inhibitory protein (c-FLIP) in KBD was significantly downregulated. Conclusions. KBD and OA chondrocytes showed obvious FADD-caspase-dependent apoptosis, which is related to the DR pathway. Apoptosis in KBD articular cartilage is mainly related to FAS/DR4-FADD-caspase signaling, and OA is associated with FAS/DR4/DR5-FADD-caspase signaling.