Development and validation of nomograms for predicting prognosis in patients with solitary HCC: A TRIPOD-Compliant study.

Objective: To develop and validate nomograms for predicting the OS and CSS of patients with Solitary Hepatocellular Carcinoma (HCC). Methods: Using the TRIPOD guidelines, this study identified 5206 patients in the Surveillance, Epidemiology, and End Results (SEER) 17 registry database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 3646) and a validation cohort (n = 1560), and the Chinese independent cohort (n = 307) constituted the external validation group. The prognosis-related risk factors were selected using univariate Cox regression analysis, and the independent prognostic factors of OS and CSS were identified using the Lasso-Cox regression model. The nomograms for predicting the OS and CSS of the patients were constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve in both the training and validation cohorts. Results: We identified factors that predict OS and CSS and constructed two nomograms based on the data. The ROC analysis, C-index analysis, and calibration analysis indicated that the two nomograms performed well over the 1, 3, and 5-year OS and CSS periods in both the training and validation cohorts. Additionally, these results were confirmed in the external validation group. Decision curve analysis (DCA) demonstrated that the two nomograms were clinically valuable and superior to the TNM stage system. Conclusion: We established and validated nomograms to predict 1,3, and 5-year OS and CSS in solitary HCC patients, and our results may also be helpful for clinical decision-making.

Axon-like aligned conductive CNT/GelMA hydrogel fibers combined with electrical stimulation for spinal cord injury recovery.

Rehabilitation and regenerative medicine are two promising approaches for spinal cord injury (SCI) recovery, but their combination has been limited. Conductive biomaterials could bridge regenerative scaffolds with electrical stimulation by inducing axon regeneration and supporting physiological electrical signal transmission. Here, we developed aligned conductive hydrogel fibers by incorporating carbon nanotubes (CNTs) into methacrylate acylated gelatin (GelMA) hydrogel via rotating liquid bath electrospinning. The electrospun CNT/GelMA hydrogel fibers mimicked the micro-scale aligned structure, conductivity, and soft mechanical properties of neural axons. For in vitro studies, CNT/GelMA hydrogel fibers supported PC12 cell proliferation and aligned adhesion, which was enhanced by electrical stimulation (ES). Similarly, the combination of aligned CNT/GelMA hydrogel fibers and ES promoted neuronal differentiation and axon-like neurite sprouting in neural stem cells (NSCs). Furthermore, CNT/GelMA hydrogel fibers were transplanted into a T9 transection rat spinal cord injury model for in vivo studies. The results showed that the incorporating CNTs could remain at the injury site with the GelMA fibers biodegraded and improve the conductivity of regenerative tissue. The aligned structure of the hydrogel could induce the neural fibers regeneration, and the ES enhanced the remyelination and axonal regeneration. Behavioral assessments and electrophysiological results suggest that the combination of aligned CNT/GelMA hydrogel fibers and ES could significantly restore motor function in rats. This study demonstrates that conductive aligned CNT/GelMA hydrogel fibers can not only induce neural regeneration as a scaffold but also support ESto promote spinal cord injury recovery. The conductive hydrogel fibers enable merging regenerative medicine and rehabilitation, showing great potential for satisfactory locomotor recovery after SCI.

Changes in the centre of rotation and the anterior bone loss of the vertebral body in Mobi-C artificial disc replacement segments after cervical hybrid surgery: a retrospective study.

OBJECTIVE: To examine the short-term efficacy and imaging results of using the Mobi-C in cervical hybrid surgery on 2-level cervical spondylolisthesis. To observe post-operative changes in the flexion-extension centre of rotation (FE-COR) and anterior bone loss (ABL) of the anterior cervical disc replacement (ACDR) segment. METHODS: Forty-two patients (20 males and 22 females, aged 42‒67 years) who underwent cervical hybrid surgery were retrospectively analysed. Their ACDR segment used Mobi-C, and the fusion segment used ROI-C, with a follow-up of 25‒42 months (31.1 ± 4.8 months). The modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and visual analogue scale (VAS) were used to assess clinical outcomes. Pre-operative, 6-month post-operative, and final follow-up radiographs were collected to compare total cervical spine curvature (C2-C7), curvature of the operated segments, range of motion (ROM) in the total cervical spine, operated segmental ROM, ACDR segmental ROM, and operated adjacent segmental ROM. The height of the superior articular process (HSAP), the orientation of zygapophyseal joint spaces (OZJS), and the length of the superior articular surface (LSAS) were measured. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The translation distance of the Mobi-C was measured. The degree of disc degeneration in the adjacent segment, bony fusion of the ACDF segment, and ABL of the upper and lower vertebra of the ACDR segment were observed. RESULTS: In our group, all patients have shown improvements in their postoperative mJOA, NDI, and VAS scores. Overall cervical ROM and surgical segmental ROM decreased (P < 0.05). However, there was no significant decrease in ACDR segmental ROM and upper or lower adjacent segmental ROM compared with pre-operatively (P > 0.05). For FE-COR-X, only the last follow-up compared with pre-surgery showed statistical significance (46.74 ± 7.71% vs. 50.74 ± 6.92%, P < 0.05). For FE-COR-Y, the change was statistically significant at both 6 months post-operation and the final follow-up compared to pre-operation (45.37% ± 21.11% vs. 33.82% ± 10.87%, 45. 37% ± 21.11% vs. 27.48% ± 13.58%, P < 0.05). No significant difference in the Mobi-C translation distance was observed (P > 0.05). Moreover, the difference in HSAP was not statistically significant at each node (P > 0.05). The OZJS and LSAS were significantly different at the final follow-up compared to the pre-operative period (P < 0.05). All the ACDF segments were observed in a stable condition at the final follow-up. Furthermore, 9 of the adjacent segments showed imaging ASD (9/82, 10.98%), and all were present at the last follow-up, of which 6 were mild, and 3 were moderate. Twenty of the 42 Mobi-C segments had no significant ABL (grade 0) 6 months post-operatively (47.62%). Sixteen cases (38.10%) showed mild ABL (grade 1), and 6 cases (14.28%) showed moderate ABL (grade 2). No severe ABL occurred. CONCLUSION: The cervical hybrid surgery using Mobi-C artificial cervical discs can achieve satisfactory results. The Mobi-C segmental FE-COR-X shows a slow forward shift trend, and FE-COR-Y drops noticeably within 6 months post-surgery before stabilizing. It's common to see mild to moderate ABL after cervical hybrid surgery using Mobi-C, and significant progression is unlikely in the short term. Furthermore, changes in the FE-COR after hybrid surgery in the Mobi-C segment might not affect clinical outcomes.

Correction to "Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells".

[This corrects the article on p. 1968 in vol. 14, PMID: 36310707.].

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Polyetheretherketone (PEEK) rods versus titanium rods for posterior lumbar fusion surgery: a systematic review and meta-analysis.

BACKGROUND: Rigid fixation, represented by titanium rods, is a widely used fixation technique for lumbar fusion. However, this technique carries the risk of degeneration of adjacent segments. In recent years, the semi-rigid fixation technique represented by PEEK rods has gradually matured, and its effectiveness has been verified by numerous studies. The aim of this study was to systematically evaluate the effectiveness of these two fixation modalities in posterior lumbar fusion surgery. METHODS: Studies meeting the inclusion criteria were searched in PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang databases. After data extraction and quality assessment of included studies, meta-analysis was performed using STATA 15.1 software. The protocol for this systematic review was registered on INPLASY (2021110049) and is available in full on the inplasy.com ( https://inplasy.com/inplasy-2021-11-0049/ ). RESULTS: Fifteen relevant studies were finally included, including eight prospective studies and seven retrospective studies. The results of meta-analysis showed that in ODI (P = 0.000), JOA score (P = 0.017), VAS score for lower limb pain (P = 0.027), fusion rate of bone graft at week 12 (P = 0.001), fusion rate of bone graft at last follow-up (P = 0.028), there was a statistical difference between the two groups. The PEEK rod group was superior to the titanium rod group in the above aspects. While in VAS score for LBP (P = 0.396), there was no statistical difference between the two groups. CONCLUSION: Both PEEK rods and titanium rods are effective fixation materials in lumbar fusion surgery. PEEK rods may be superior to titanium rods in improving postoperative function and improving bone graft fusion rates. However, given the limitations of this study, whether these conclusions are applicable needs further research.

QTLs Related to Rice Callus Regeneration Ability: Localization and Effect Verification of qPRR3.

Mature and efficient tissue culture systems are already available for most japonica rice varieties (Oryza sativa ssp. geng). However, it remains challenging to regenerate the majority of indica rice varieties (Oryza sativa ssp. xian). In this study, quantitative trait loci (QTLs) associated with rice callus regeneration ability were identified based on the plant regeneration rate (PRR) and total green plant rate (TGPR) of the 93-11 × Nip recombinant inbred line population. Significant positive correlations were found between PRR and TGPR. A total of three QTLs (one for PRR and two for TGPR) were identified. qPRR3 (located on chromosome 3) was detected for both traits, which could explain 13.40% and 17.07% of the phenotypic variations of PRR and TGPR, respectively. Subsequently, the effect of qPRR3 on callus regeneration ability was validated by cryptographically tagged near-isogenic lines (NILs), and the QTL was narrowed to an interval of approximately 160 kb. The anatomical structure observation of the regenerated callus of the NILs revealed that qPRR3 can improve the callus regeneration ability by promoting the regeneration of shoots.

Improvement of Rice Agronomic Traits by Editing Type-B Response Regulators.

Type-B response regulator proteins in rice contain a conserved receiver domain, followed by a GARP DNA binding domain and a longer C-terminus. Some type-B response regulators such as RR21, RR22 and RR23 are involved in the development of rice leaf, root, flower and trichome. In this study, to evaluate the application potential of type-B response regulators in rice genetic improvement, thirteen type-B response regulator genes in rice were respectively knocked out by using CRISPR/Cas9 genome editing technology. Two guide RNAs (gRNAs) were simultaneously expressed on a knockout vector to mutate one gene. T0 transformed plants were used to screen the plants with deletion of large DNA fragments through PCR with specific primers. The mutants of CRISPR/Cas9 gene editing were detected by Cas9 specific primer in the T1 generation, and homozygous mutants without Cas9 were screened, whose target regions were confirmed by sequencing. Mutant materials of 12 OsRRs were obtained, except for RR24. Preliminary phenotypic observation revealed variations of various important traits in different mutant materials, including plant height, tiller number, tillering angle, heading date, panicle length and yield. The osrr30 mutant in the T2 generation was then further examined. As a result, the heading date of the osrr30 mutant was delayed by about 18 d, while the yield was increased by about 30%, and the chalkiness was significantly reduced compared with those of the wild-type under field high temperature stress. These results indicated that osrr30 has great application value in rice breeding. Our findings suggest that it is feasible to perform genetic improvement of rice by editing the type-B response regulators.

Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells.

BACKGROUND: Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated. AIM: To investigate whether and how IL-34 affects the proliferation of GC cells and EMT. METHODS: Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting. RESULTS: Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice. CONCLUSION: IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

Evaluation of the Efficacy of Stem Cell Therapy in Animal Models of Intervertebral Disc Degeneration Based on Imaging Indicators: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to make a systematic review of the therapeutic effect of stem cells in animal models of disc degeneration from an imaging point of view. Methods: Data were extracted by searching electronic databases for RCTs that met the inclusion criteria. Data analysis was performed using RevMan 5.3 and STATA 15.1 software. This meta-analysis was registered with INPLASY, registration number INPLASY202240148. Results: A total of 34 studies were included, covering four species of animals, rabbits, sheep, rats, and mice, with a total of 1163 intervertebral discs. In terms of DHI, the efficacy of stem cell group in rabbits (P < 0.001), mice (P < 0.001), sheep (P < 0.001), and rats (P = 0.001) was better than that in control group. In terms of disc height, the efficacy of stem cell group in rats (P < 0.001) was better than that in control group, while in sheep (P = 0.355), there was no statistical difference between two groups. In terms of MRI index, the efficacy of stem cell group in rats (P < 0.001), mice (P < 0.001), and rabbits (P = 0.016) was better than that in control group. In terms of MRI signal score, the efficacy of stem cell group in rabbits (P < 0.001) was better than that of control group. In terms of T2 signal intensity, stem cell group was more effective than control group in rabbits (P < 0.001), mice (P < 0.001), and rats (P = 0.003). Conclusion: Stem cell therapy can improve intervertebral disc-related imaging parameters in animal models of disc degeneration, indicating that stem cell therapy has a repairing effect on intervertebral discs. However, given the heterogeneity and limitations of this study, this conclusion still needs to be tested by a large number of studies.

Mid-long-term follow-up of operated level kinematics after single-level artificial cervical disc replacement with Bryan disc.

OBJECTIVE: Evaluation of the mid-long-term kinematics of single-level Bryan artificial cervical disc replacement (ACDR) in vivo by analyzing the center of rotation (COR) at the operated level. METHODS: A retrospective analysis was conducted using data collected from 38 patients who underwent single-level Bryan ACDR from January 2010 to March 2013. Radiological parameters including range of motion (ROM), lordosis angle, translation, and COR were obtained. Clinical outcomes were assessed based on Odom Criteria, modified Japanese Orthopedic Association (mJOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) scores. Correlations between COR and other follow-up data were discussed at the last follow-up. RESULTS: Compared with preoperative values, the last follow-up data showed that 86.84% of cases achieved good-or-excellent outcomes based on Odom criteria; Significant improvements were observed across all scales assessed for clinical outcomes (P < 0.05); Lordosis angle was significantly increased in both the overall cervical spine and the operated level (P < 0.05); ROM of the overall cervical spine, operated level, and adjacent levels was preserved (P > 0.05); There was no significant change in COR at the operated level (P > 0.05). At the last follow-up and at the operated level, COR (Y) showed negative correlations with ROM and translation (P < 0.05), but no follow-up data correlated with COR (X) were found (P > 0.05). CONCLUSIONS: Satisfactory clinical and radiological outcomes were achieved 7 years or more after single-level Bryan ACDR. At the operated level, preoperative COR was maintained, probably due to replicating the physiological interrelations of COR (Y), translation, and ROM.

Effects of posterior lumbar nonfusion surgery with isobar devices versus posterior lumbar interbody fusion surgery on clinical and radiological features in patients with lumbar degenerative diseases: a meta-analysis.

PURPOSE: The aim of this study was to systematically evaluate the efficacy of posterior lumbar isobar nonfusion with isobar devices versus posterior lumbar interbody fusion (PLIF) in the treatment of patients with lumbar degenerative diseases (LDDs). MATERIALS AND METHOD: We performed a literature review and meta-analysis in accordance with the Cochrane methodology. The analysis included a Group Reading Assessment and Diagnostic Evaluation assessments, Jadad Quality Score evaluations, and Risk of Bias in Randomized Studies of Interventions assessments. The PubMed, Ovid, EMBASE, Web of Science, MEDLINE, CNKI, VIP and WanFang databases were searched to collect and compare relevant randomized controlled trials and cohort studies of isobar nonfusion and PLIF in the treatment of lumbar degenerative diseases. The retrieval time was from database inception to June 2021. Two evaluators independently screened the literature, extracted data, and evaluated the quality of the included studies. Outcome measures of interest included low back pain, disability, and radiological features. The protocol for this systematic review was registered on INPLASY (2021110059) and is available in full on inplasy.com ( https://inplasy.com/inplasy-2021-11-0059/ ). RESULTS: Of the 7 RCTs, 394 patients met the inclusion criteria. The meta-analysis results showed that isobar nonfusion surgery shortened the surgical duration (P = 0.03), reducing intraoperative bleeding (P = 0.001), retained the ROM of surgical segment (P < 0.00001) and the ROM of the lumbar spine (P < 0.00001), and reduced the incidence of ASD (P = 0.0001). However, no significant difference in the postoperative ODI index (P = 0.81), VAS score of LBP (P = 0.59, VAS score of lower limb pain (P = 0.05, and JOA score (P = 0.27) was noted. CONCLUSIONS: Posterior lumbar nonfusion surgery with isobar devices is superior to PLIF in shortening the surgical duration, reducing intraoperative bleeding, retaining the ROM of surgical segments and the lumbar spine to a certain extent, and preventing ASD. Given the possible publication bias, we recommend further large-scale studies.

Nomograms for Predicting the Lymph Node Metastasis in Early Gastric Cancer by Gender: A Retrospective Multicentric Study.

BACKGROUND: Lymph node metastasis (LNM) has a significant impact on the prognosis of patients with early gastric cancer (EGC). Our aim was to identify the independent risk factors for LNM and construct nomograms for male and female EGC patients, respectively. METHODS: Clinicopathological data of 1,742 EGC patients who underwent radical gastrectomy and lymphadenectomy in the First Affiliated Hospital, Second Affiliated Hospital, and Fourth Affiliated Hospital of Anhui Medical University between November 2011 and April 2021 were collected and analyzed retrospectively. Male and female patients from the First Affiliated Hospital of Anhui Medical University were assigned to training sets and then from the Second and Fourth Affiliated Hospitals of Anhui Medical University were enrolled in validation sets. Based on independent risk factors for LNM in male and female EGC patients from the training sets, the nomograms were established respectively, which was also verified by internal validation from the training sets and external validation from the validation sets. RESULTS: Tumor size (odd ratio (OR): 1.386, p = 0.030), depth of invasion (OR: 0.306, p = 0.001), Lauren type (OR: 2.816, p = 0.000), lymphovascular invasion (LVI) (OR: 0.160, p = 0.000), and menopause (OR: 0.296, p = 0.009) were independent risk factors for female EGC patients. For male EGC patients, tumor size (OR: 1.298, p = 0.007), depth of invasion (OR: 0.257, p = 0.000), tumor location (OR: 0.659, p = 0.002), WHO type (OR: 1.419, p = 0.001), Lauren type (OR: 3.099, p = 0.000), and LVI (OR: 0.131, p = 0.000) were independent risk factors. Moreover, nomograms were established to predict the risk of LNM for female and male EGC patients, respectively. The area under the ROC curve of nomograms for female and male training sets were 87.7% (95% confidence interval (CI): 0.8397-0.914) and 94.8% (95% CI: 0.9273-0.9695), respectively. For the validation set, they were 92.4% (95% CI: 0.7979-1) and 93.4% (95% CI: 0.8928-0.9755), respectively. Additionally, the calibration curves showed good agreements between the bias-corrected prediction and the ideal reference line for both training sets and validation sets in female and male EGC patients. CONCLUSIONS: Nomograms based on risk factors for LNM in male and female EGC patients may provide new insights into the selection of appropriate treatment methods.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma.

Background: Malignant pheochromocytoma and paraganglioma (PPGL) are rare tumors with few prognostic tools. This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. Methods: The patient data was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 764 patients diagnosed with malignant PPGL from 1975 to 2016 were included in this study. The patients were randomly divided into two cohorts; the training cohort (n = 536) and the validation cohort (n = 228). Univariate analysis, Lasso regression, and multivariate Cox analysis were used to identify independent prognostic factors, which were then utilized to construct survival nomograms. The nomograms were used to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) for patients with malignant PPGL. The prediction accuracy of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCAs) was used to evaluate the performance of survival models. Results: Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). Based on these factors, we successfully constructed the OS and CSS nomograms. The C-indexes were 0.747 and 0.742 for the OS and CSS nomograms, respectively. In addition, both the calibration curves and ROC curves for the model exhibited reliable performance. Conclusion: We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL. The nomograms could inform personalized clinical management of the patients.

Using the cobweb classification system as a digital location system for the neurologic compression in cervical degenerative disease.

OBJECTIVE: To provide the cobweb classification system (CCS) for the precise digital location and description of the neurological compression in cervical degenerative disease (CDD), and the reliability and the clinical subgroup analysis of the system were tested and analyzed. METHODS: The CCS consisted of three parts: compression zones (1-12), degrees (a, b) and ossification (s, m, h). Computerized tomography (CT) and magnetic resonance imaging (MRI) images from 238 CDD patients were reviewed. All compression cases were classified by five independent reviewers with varied clinical experience in spine surgery. The reliability of the CCS was tested by calculating the kappa (κ) statistics value. Finally, 74 patients with anterior cervical surgery treatment were enrolled for the clinical subgroup analysis. RESULTS: For the small compression, including single and double compression zones, there was a good interobserver reliability between the reviewers (κ coefficient = .855, P < .001). For the large compression with three or more involved zones, there was a fair reliability between the reviewers (κ coefficient = .696, P < .001). The whole intraobserver reliability was good (κ coefficient = .923, P < .001). For clinical practice, the operative time in the large compression and the m/h group was significantly longer than the small compression and the s group, respectively (P < .05), and the blood loss in the m/h group was significantly increased as well (P < .01). Though the preoperative Japanese Orthopedic Association score in Group b was lower than Group a (P < .05), all patients had achieved significant clinical improvement at last follow-up. CONCLUSIONS: The CCS can be used to provide detailed and objective descriptions of the location, extent, and severity of neurological compressions in CDD with satisfactory reliability. Surgeons should pay more attention to the patient with large zone, degree b, and ossification compression, because the operation may be more challenging.

A comparison study between hybrid surgery and anterior cervical discectomy and fusion for the treatment of multilevel cervical spondylosis.

AIMS: Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition. METHODS: Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom's criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger's and Begg's tests, meta-regression, and sensitivity analyses were performed. RESULTS: In total, 17 studies involving 861 patients were included in the analysis. HS was found to be superior to ACDF in maintaining C2-C7 ROM and ROM of superior/inferior adjacent levels, but HS did not reduce the incidence of associated level ASD. Also, HS did not cause a higher rate of HO than ACDF. The frequency of complications was similar between the two techniques. HS failed to achieve more favourable outcomes than ACDF using the NDI, VAS, JOA, and Odom's scores. HS did not show any more advantages in operating or hospitalization time but did show reduction in blood loss. CONCLUSION: Although HS maintained cervical kinetics, it failed to reduce the incidence of ASD. This finding differs from previous reports. Moreover, patients did not show more benefits from HS with respect to symptom improvement, prevention of complications, and clinical outcomes. Cite this article: Bone Joint J 2020;102-B(8):981-996.

Translocation of Drought-Responsive Proteins from the Chloroplasts.

Some chloroplast proteins are known to serve as messengers to transmit retrograde signals from chloroplasts to the nuclei in response to environmental stresses. However, whether particular chloroplast proteins respond to drought stress and serve as messengers for retrograde signal transduction are unclear. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) to monitor the proteomic changes in tobacco (Nicotiana benthamiana) treated with drought stress/re-watering. We identified 3936 and 1087 differentially accumulated total leaf and chloroplast proteins, respectively, which were grouped into 16 categories. Among these, one particular category of proteins, that includes carbonic anhydrase 1 (CA1), exhibited a great decline in chloroplasts, but a remarkable increase in leaves under drought stress. The subcellular localizations of CA1 proteins from moss (Physcomitrella patens), Arabidopsis thaliana and rice (Oryza sativa) in P. patens protoplasts consistently showed that CA1 proteins gradually diminished within chloroplasts but increasingly accumulated in the cytosol under osmotic stress treatment, suggesting that they could be translocated from chloroplasts to the cytosol and act as a signal messenger from the chloroplast. Our results thus highlight the potential importance of chloroplast proteins in retrograde signaling pathways and provide a set of candidate proteins for further research.

Identification of Key Pathways and Genes in L4 Dorsal Root Ganglion (DRG) After Sciatic Nerve Injury via Microarray Analysis.

Background: Peripheral nerve injury (PNI) has devastating consequences. Dorsal root ganglion as a pivotal locus participates in the process of neuropathic pain and nerve regeneration. In recent years, gene sequencing technology has seen rapid rise in the biomedicine field. So, we attempt to gain insight into in the mechanism of neuropathic pain and nerve regeneration in the transcriptional level and to explore novel genes through bioinformatics analysis. Methods: The gene expression profiles of GSE96051 were downloaded from GEO database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. Results: Our results showed that both IL-6 and Jun genes and the signaling pathway of MAPK, apoptosis, P53 present their vital modulatory role in nerve regeneration and neuropathic pain. Noteworthy, 13 hub genes associated with neuropathic pain and nerve regeneration, including Ccl12, Ppp1r15a, Cdkn1a, Atf3, Nts, Dusp1, Ccl7, Csf, Gadd45a, Serpine1, Timp1 were rarely reported in PubMed database, these genes may provide us the new orientation in experimental research and clinical study. Conclusions: Our results may provide more deep insight into the mechanism and a promising therapeutic target. The next step is to put our emphasis on an experiment level and to verify the novel genes from 13 hub genes.

Dynamic Fusion Process in the Anterior Cervical Discectomy and Fusion with Self-Locking Stand-Alone Cages.

BACKGROUND: Self-locking stand-alone cages can achieve satisfactory clinical results and fusion rate. However, there have been no reports on the causes and relationship of different fusion state. This study is to classify the different fusion states of the index level and to explore the potential contributing factors and links of them. METHODS: From June 2008 to October 2011, 42 patients underwent anterior cervical discectomy and fusion with MC+ cages. More than 5 years' follow-up was reviewed. The fusion state and the relevant clinical and radiologic records were reviewed retrospectively. RESULTS: At the last follow-up, the fusion proportion of type I, II, III, and IV was 11.7%, 16.9%, 26.9%, and 42.9%, respectively. The overall fusion rate was 97.4%. For all the fused types, significant improvement for the visual analog scale, Japanese Orthopaedic Association, and Neck Disability Index scores was found at the last follow-up (P < 0.05). However, there were no significant differences between the 4 types (P > 0.05). For sagittal vertical axis, type IV was significantly larger than that of type I, II, and III (P < 0.05), and for range of motion, type III was significantly larger than that of type II and IV (P < 0.05). CONCLUSIONS: For anterior cervical discectomy and fusion with self-locking stand-alone cages, the fusion of the index level seems to be a progressive dynamic process during the mid-term follow-up, which may be influenced by the location of the cage, the aagittal vertical axis of the index level, and the global range of motion of the cervical spine. Satisfactory clinical results could be achieved by all the fused types.

miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells.

BACKGROUND/AIMS: Osteoporosis is a bone metabolic disease characterized by a systemic impairment of bone mass, which results in increased propensity of fragility fractures. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. Mesenchymal stem cells (MSCs) are induced to differentiate into preosteoblasts, which are regulated by the signaling cascades initiated by the various signals, including miRNAs. miR-16-2* is a newly discovered miRNA that participates in diagnosis and prognosis of hepatocellular carcinoma, cervical cancer and chronic lymphocytic leukemia. However, the effect of miR-16-2* on the regulation of osteoblast differentiation and the mechanism responsible are still unclear. Here we discuss the contribution of miR-16-2* to osteoporosis, osteoblast differentiation and mineralization. METHODS: The expression pattern of miR-16-2* during osteogenesis or in osteoporosis bone samples was validated by quantitative real-time PCR (qRT-PCR). The human bone marrow mesenchymal stem cells (hBMSCs) were induced to differentiate into osteoblasts by osteogenic induced medium containing dexamethasone, ascorbate-2-phosphat, beta-glycerophosphate and vitamin-D3. The target genes of miR-16-2* were predicted by TargetScan and PicTar. The mRNA and protein levels of osteogenic key markers were detected using qRT-PCR or western blot respectively. The WNT signal activity was analyzed by TOP/FOP reporter assay. RESULTS: The expression of miR-16-2* in patient bone tissue with osteoporosis was negatively correlated with bone formation related genes. During osteoblast differentiation process, the expression of miR-16-2* was significantly decreased. Upregulation of miR-16-2* in hBMSCs impaired the osteogenic differentiation while the downregulation of miR-16-2* increased this process. Upregulation the expression of miR-16-2* could also block the WNT signal pathway by directly target WNT5A. Furthermore, knockdown of miR-16-2* could promote the activation of RUNX2, possibly by lifting the inhibitory effect of miR-16-2* on WNT pathway. CONCLUSION: Taken together, we report a novel biological role of miR-16-2* in osteogenesis through regulating WNT5A response for the first time. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.