A novel lncRNA GM15416 regulates osteoblast apoptosis and differentiation through the c-Fos/Fas axis and mitigates osteoporosis.

Osteoporosis (OP) is a common systemic bone disorder, and the programmed cell death of osteoblasts is closely linked to the development of osteoporosis. Previous studies have shown that c-fos can cause osteoblast apoptosis. Furthermore, it has been demonstrated that long non-coding RNA (lncRNA) plays a pervasive role in regulating the biology of osteoblasts. Nevertheless, the precise role and mechanism of long non-coding RNA (lncRNA) in relation to c-Fos at the transcriptional level in osteoblast cell death remain uncertain. Compared with normal osteoblasts, serum deprivation resulted in significant upregulation of the transcription factor c-Fos and apoptosis-related Fas proteins in osteoblasts. In addition, the expression of lncRNA GM15416 related to c-Fos was significantly increased. The results showed that overexpression of c-Fos leads to an increase in downstream Fas protein, which subsequently leads to osteoblast apoptosis and hinders osteogenesis. On the contrary, a decrease in lncRNA GM15416 expression leads to a decrease in c-Fos/Fas expression, which hinders osteoblast apoptosis and promotes osteogenesis. Our results suggest that lncRNA GM15416 exerts inhibitory effects on osteoblast apoptosis and acts as a preventive factor against osteoporosis. As a result, GM15416 emerges as an important lncRNA associated with osteoporosis and holds potential as a future therapeutic target.

[Application of cartilage in tympanoplasty].

Cartilage has undergone rapid development in ear surgery since Heermann used the grid cartilage technique to repair large perforations of the tympanic membrane. Cartilage has been widely used in tympanoplasty, ossicular chain reconstruction, reconstruction of the lateral wall of the upper tympanic cavity and the posterior wall of the external auditory canal due to its advantages of convenient sampling, high stability, good elasticity, low metabolic rate, easy survival and strong plasticity. This paper reviews the use of cartilage in tympanoplasty and discusses the possibility of placing cartilage on the stapes head for reconstruction of the auditory chain in type Ⅱ tympanoplasty.

Clinical Efficacy of Posterior Percutaneous Endoscopic Unilateral Laminotomy with Bilateral Decompression for Symptomatic Cervical Spondylotic Myelopathy.

OBJECTIVE: To compare the clinical efficacy of posterior percutaneous endoscopic unilateral laminotomy (PPEUL) and anterior cervical decompression and fusion (ACDF) in the treatment of single-segment spondylotic myelopathy (CSM). METHODS: This is a retrospective research, from January 2017 to December 2019, 30 cases were included in the PPEUL group and 32 cases were included in the ACDF group. The operative duration, blood loss, length of stay, complications, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, MacNab classification and imaging data were collected preoperatively, postoperative 1-week, final follow-up and statistically analyzed. RESULTS: The surgery was completed successfully on all patients, and there were no serious complications, such as nerve or spinal cord injury or infection. In the PPEUL and ACDF groups, the operative duration were 56.63 ± 1.40 and 65.21 ± 2.45 min, the intraoperative blood loss were 51.69 ± 3.23 and 50.51 ± 5.48 mL, and the hospitalization duration was 5.75 ± 1.43 and 6.38 ± 2.16 days. The follow-up period in the PPEUL and ACDF groups was 24.96 ± 1.12 months and 25.65 ± 1.45 months, respectively. There was no significant difference in intraoperative blood loss between the two groups, but the hospitalization and operative durations in the PPEUL group were significantly shorter than those in the ACDF group (P < 0.05). The VAS scores at postoperative 1 week and final follow-up were significantly improved compared with those before surgery. The JOA scores at postoperative 1 week and final follow-up were significantly improved compared with those before surgery, but there was no significant difference between the two groups at the last follow-up. The intervertebral disc height of the adjacent segment at the last follow-up was significantly lower in the ACDF group than in the PPEUL group (P < 0.05), but there was no significant difference between the two groups in the intervertebral disc height of the surgical segment (P > 0.05). The rate of excellent and good results was 90.0% and 87.5%, respectively. Postoperative cervical CT and MRI showed that the spinal canal was fully decompressed and spinal cord compression was relieved. CONCLUSION: PPEUL has the advantages of reduced trauma, rapid recovery and remarkable curative efficacy, so it is a new choice for the treatment of CSM.

Semiparametric analysis of multivariate panel count data with nonlinear interactions.

Multivariate panel count data frequently arise in follow up studies involving several related types of recurrent events. For univariate panel count data, several varying coefficient models have been developed. However, varying coefficient models for multivariate panel count data remain to be studied. In this paper, we propose a varying coefficient mean model for multivariate panel count data to describe the possible nonlinear interact effects between the covariates and the local logarithm partial likelihood procedure is considered to estimate the unknown covariate effects. Furthermore, a Breslow-type estimator is constructed for the baseline mean functions. The consistency and asymptotic normality of the proposed estimators are established under some mild conditions. The utility of the proposed approach is evaluated by some numerical simulations and an application to a dataset of skin cancer study.

New Hope for Intervertebral Disc Degeneration: Bone Marrow Mesenchymal Stem Cells and Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Transplantation.

Bone Marrow Mesenchymal Stem Cells (BMSCs), multidirectional cells with self-renewal capacity, can differentiate into many cell types and play essential roles in tissue healing and regenerative medicine. Cell experiments and in vivo research in animal models have shown that BMSCs can repair degenerative discs by promoting cell proliferation and expressing Extracellular Matrix (ECM) components, such as type II collagen and protein-polysaccharides. Delaying or reversing the Intervertebral Disc Degeneration (IDD) process at an etiological level may be an effective strategy. However, despite increasingly in-depth research, some deficiencies in cell transplantation timing and strategy remain, preventing the clinical application of cell transplantation. Exosomes exhibit the characteristics of the mother cells from which they are secreted and can inhibit Nucleus Pulposus Cell (NPC) apoptosis and delay IDD through intercellular communication. Furthermore, the use of exosomes effectively avoids problems associated with cell transplantation, such as immune rejection. This manuscript introduces almost all of the BMSCs and exosomes derived from BMSCs (BMSCs-Exos) described in the IDD literature. Many challenges regarding the use of cell transplantation and therapeutic exosome intervention for IDD remain to be overcome.

Application of Triggered EMG in the Intraoperative Neurophysiological Monitoring of Posterior Percutaneous Endoscopic Cervical Discectomy.

OBJECTIVE: To describe the rationale and application of triggered EMG (T-EMG) in intraoperative neurophysiological monitoring, and to explore the efficacy and safety of posterior percutaneous endoscopic cervical discectomy (PPECD) in the treatment of cervical spondylotic radiculopathy (CSR) under multimodal intraoperative neurophysiological monitoring (IOM). METHODS: This study was a retrospective cohort control study. The clinical data of 74 patients with single-segment CSR from June 2015 to August 2018 were analyzed retrospectively, of whom 35 underwent IOM-assisted PPECD with triggered EMG (T-EMG group), while 39 were subjected to IOM-assisted PPECD alone (IOM group). Operation time, hospital stay, and complications were recorded for both groups. The curative effect was evaluated according to the Visual Analog Scale (VAS) of neck and arm pain, Japanese Orthopaedic Association (JOA) score, and modified MacNab scale. RESULTS: Operations were successful and all patients were followed up for at least 24 (average 31.77 ± 9.51) months with no patient lost to follow-up. No significant difference was found in preoperative baseline data between the T-EMG and the IOM group (P > 0.05). Also, no significant difference was found in the operation time between the T-EMG (108.29 ± 11.44 min) and the IOM (110.13 ± 12.70 min) (P > 0.05) group, but the difference in hospital stay (T-EMG: 5.66 ± 0.99 days; IOM: 7.10 ± 1.43 days) was statistically significant (P < 0.05). The VAS for the neck and upper limbs in the two groups at 1 month post-operation (T-EMG: 2.09 ± 1.07, 2.26 ± 0.92; IOM:2.18 ± 1.05, 2.31 ± 0.77) and the last follow-up (T-EMG: 0.83 ± 0.62, 0.86 ± 0.55; IOM: 0.90 ± 0.50, 0.87 ± 0.61) were significantly different from the preoperative scores (T-EMG: 6.14 ± 1.09, 7.17 ± 1.04; IOM: 6.18 ± 1.28, 7.15 ± 1.23) (P < 0.05). However, no significant difference was found between the two groups (P > 0.05). The 1-month postoperative JOA scores for the two groups (12.69 ± 0.76; 12.59 ± 0.82) and those at the last follow-up (14.60 ± 0.77; 14.36 ± 0.78) were significantly different from the preoperative scores (11.09 ± 0.98; 11.05 ± 0.89) (P < 0.05), but the difference between the two groups was not significant (P > 0.05). One patient in the T-EMG group developed a transient aggravation of symptoms on the first day after surgery. In the IOM group, three patients had intraoperative cerebrospinal fluid leakage, and symptoms of C5 nerve root paralysis were presented in four patients following surgery. Compared with the IOM group, the T-EMG group had fewer complications (1/35; 7/39, P < 0.05). At the last follow-up, the modified MacNab criteria were 91.43% (32/35) and 89.7% (35/39) for the T-EMG group and IOM group, respectively. CONCLUSIONS: Triggered EMG prevents the occurrence of neurological complications, which not only aids PPECD for CSR treatment in achieving satisfactory results, but also reduces average hospital stay and complication rates.

Percutaneous Endoscopic Unilateral Laminotomy and Bilateral Decompression for Lumbar Spinal Stenosis.

To introduce a new surgery, percutaneous endoscopic unilateral laminotomy and bilateral decompression (Endo-ULBD) using visual trepan, and investigate its efficacy and safety in elderly patients with lumbar spinal stenosis. In our retrospective study, a total of 69 patients were enrolled between March 2018 and September 2018; 31 patients were treated with Endo-ULBD and 38 patients were treated with posterior lumbar interbody fusion surgery (PLIF). The operation time, intraoperative blood loss, and hospitalization duration were compared between the two groups. A visual analog scale (VAS) was used to evaluate the degree of pain. The Oswestry Disability Index (ODI) and European Quality of Life-5 Dimensions (EQ-5D) were used to evaluate lumbar function and quality of life, respectively. Lumbar X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) were performed postoperatively at different time points. MacNab's outcome assessment and perioperative complications were also documented. The surgeon completed all surgeries successfully, and all 69 patients were followed up. The operative time of the Endo-ULBD group was 60.68 ± 0.47 min, while that of the PLIF group was 120.23 ± 10.24 min. The operative time of the Endo-ULBD group was shorter than that of the PLIF group, and the difference was statistically significant (P < 0.001). The volume of intraoperative blood loss was 47.25 ± 0.43 mL in the Endo-ULBD group and 256.90 ± 20.83 mL in the PILF group (P < 0.001). The length of hospital stay in the Endo-ULBD group was 5.12 ± 1.60 days and that in the PILF group was 10.54 ± 1.82 days (P < 0.001). The VAS scores at postoperative 1 day, 3 months, 6 months, final follow-up (Endo-ULBD: 6.58 ± 0.65, 4.55 ± 0.54, 2.78 ± 0.24, 1.31 ± 0.78; PLIF: 7.19 ± 1.14, 4.80 ± 0.13, 2.71 ± 0.83, 1.29 ± 0.56) were significantly improved compared with those before surgery (Endo-ULBD: 8.63 ± 0.37; PLIF: 8.31 ± 1.34). The ODI and EQ-5D scores of lumbar function and quality of life at each time point after surgery (Endo-ULBD ODI: 30.29% ± 0.47%, 23.35% ± 0.95%, 19.45% ± 0.81%, 10.84% ± 0.36%; EQ-5D: 0.38 ± 0.15, 0.45 ± 0.17, 0.63 ± 0.14, 0.71 ± 0.20; PLIF ODI: 33.56% ± 1.58%, 25.69% ± 2.69%, 20.01% ± 1.49%, 10.72% ± 0.29%; EQ-5D: 0.33 ± 0.03, 0.39 ± 0.05, 0.62 ± 0.07, 0.72 ± 0.10) were significantly improved compared with those before surgery (Endo-ULBD: 44.56 ± 1.32, 0.33 ± 0.07; PLIF: 43.79 ± 1.91, 0.31 ± 0.09, respectively), with statistically significant differences (P < 0.05); however, there was no significant difference between the two groups at the last follow-up (P > 0.05). At the last follow-up, the excellent and good efficacy rate was 90.3% (28/31) in the Endo-ULBD group and 89.4% (34/38) in the PILF group (χ2 = 0.089, P = 0.993). No mortality, irreversible nerve injury, or even paralysis occurred in either group. Endo-ULBD for lumbar spinal stenosis has the advantages of less trauma, a shortened operation time, and rapid recovery and is an effective alternative for the treatment of lumbar spinal stenosis. Strict surgical indications, reasonable surgical plans, and experienced surgeons are important factors to ensure safety and satisfactory postoperative efficacy.

Early Clinical Evaluation of Percutaneous Full-endoscopic Transforaminal Lumbar Interbody Fusion with Pedicle Screw Insertion for Treating Degenerative Lumbar Spinal Stenosis.

OBJECTIVE: To compare the clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) with percutaneous pedicle screws (PPSs) performed by using a visualization system with that of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of degenerative lumbar spinal stenosis (LSS). METHODS: From June 2017 to May 2018, the data of a total of 78 patients who met the selection criteria were retrospectively reviewed and were divided into the Endo-TLIF group (40 cases) and the MIS-TLIF group (38 cases) according to the surgical method used. The visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) scale were administered preoperatively and at the 1-week, 3-month, and 1-2-year follow-ups. The fusion rate and major complications, including revision, were also recorded. RESULTS: All the patients were followed up for 24 to 34 months, with an average follow-up of 30.7 months. The intraoperative blood loss and length of hospital stay for the Endo-TLIF group (60.56 ± 0.36 mL, 8.12 ± 0.92 days, respectively) were statistically significantly lower than those for the MIS-TLIF group (65.47 ± 0.91 mL, 9.66 ± 1.34 days, respectively) (P < 0.05). The VAS and JOA scores of the patients in the two groups at postoperative 1 week, 3 months, 1 year, 2 years (Endo-TLIF VAS: 4.16 ± 0.92, 3.72 ± 1.54, 1.32 ± 0.45, 1.29 ± 0.34; JOA:16.71 ± 0.99, 19.86 ± 0.24, 24.91 ± 0.97, 25.88 ± 0.52; MIS-TLIF VAS: 4.17 ± 1.41, 2.98 ± 0.91, 1.54 ± 0.32, 1.33 ± 0.18; JOA: 16.67 ± 0.67, 19.58 ± 0.65, 25.33 ± 0.73, 25.69 ± 0.33) were statistically significantly improved from the preoperative scores (Endo-TLIF: 8.45 ± 1.44, 14.36 ± 0.56; MIS-TLIF: 8.11 ± 0.93, 14.45 ± 0.34, respectively) (P < 0.01). The VAS and JOA scores of the Endo-TLIF group were statistically significantly better than those of the MIS-TLIF group at 3 months and 1 year after surgery (P < 0.05). There were no statistically significant differences in the scores between the two groups at any of the other time points (P > 0.05). There was no significant difference in the intervertebral altitude between the two groups at the 3-month (11.36 ± 0.23, 11.21 ± 0.42, respectively) or final follow-up (10.88 ± 0.64, 10.81 ± 0.39, respectively) (P > 0.05). Dural tears, cerebrospinal fluid leakage, infection, and neurologic injury did not occur. Both groups showed good intervertebral fusion at the last follow-up. The intervertebral fusion rate was 97.5% (39/40) in the Endo-TLIF group and 94.7% (36/38) in the MIS-TLIF group, with no statistically significant difference between the two groups (χ2 = 0.118, P = 0.731). At the final follow-up, the modified MacNab's criteria were 92.5% and 89.5% between the two groups. CONCLUSION: Endo-TLIF with percutaneous pedicle screws (PPS) performed by using a visualization system for lumbar degenerative disease may be regarded as an efficient alternative surgery for degenerative lumbar spinal stenosis. It is a safe and minimally invasive way to perform this surgery and has shown satisfactory clinical outcomes.

Surgical results and prognostic factors following percutaneous full endoscopic posterior decompression for thoracic myelopathy caused by ossification of the ligamentum flavum.

Minimally invasive surgery (MIS) has shown satisfactory surgical results for the treatment of thoracic myelopathy (TM) caused by ossification of the ligamentum flavum (OLF). This study investigated the prognostic factors following MIS and was based on the retrospective analysis of OLF patients who underwent percutaneous full endoscopic posterior decompression (PEPD). Thirty single-segment OLF patients with an average age of 60.4 years were treated with PEPD under local anaesthesia. Clinical data were collected from the medical and operative records. The surgical results were assessed by the recovery rate (RR) calculated from the modified Japanese Orthopaedic Association (mJOA) score. Correlations between the RR and various factors were analysed. Patients' neurological status improved from a preoperative mJOA score of 6.0 ± 1.3 to a postoperative mJOA score of 8.5 ± 2.0 (P < 0.001) at an average follow-up of 21.3 months. The average RR was 53.8%. Dural tears in two patients (6.7%, 2/30) were the only observed complications. Multiple linear regression analysis showed that a longer duration of preoperative symptoms and the presence of a high intramedullary signal on T2-weighted MRI (T2HIS) were significantly associated with poor surgical results. PEPD is feasible for the treatment of TM patients with a particular type of OLF. Patients without T2HIS could achieve a good recovery if they received PEPD early.

A meta-analysis of interleukin-6 as a valid and accurate index in diagnosing early neonatal sepsis.

We aimed to systematically assess the overall value of interleukin 6 (IL-6) in diagnosing neonates with sepsis. A systematic literature search was conducted using the following electronic databases: PubMed, Embase, and Cochrane, to identify eligible studies through the index words updated till November 2018. Cross-sectional studies, as well as prospective cohort studies, were included in the above-mentioned group of eligible studies. We also searched the literature sources that had a link to the present study, which were further assessed by heterogeneity through the use of a proper-effects model to calculate pooled weighted specificity, sensitivity, and diagnostic odds ratio (DOR). We also conducted summary receiver operating characteristic (SROC) analyses for neonatal sepsis. In the present meta-analysis, there were 31 studies exploring IL-6 for the diagnostic accuracy of neonatal sepsis. The global specificity and sensitivity of IL-6 for neonatal sepsis were as follows: 88% (95% confidence interval [CI]: 83%-92%) and 82% (95% CI: 77%-86%), respectively. The global positive and negative likelihood ratio of IL-6 in diagnosing neonatal sepsis were 7.03 (95% CI: 4.81-10.26) and 0.20 (95% CI: 0.15-0.26), respectively. The global DOR was 29.54 (95%CI: 18.56-47.04) of IL-6. In addition, the area under the SROC was high for IL-6 (AUC = 0.92; 95% CI: 0.89-0.94). In this study, we performed a systematic review and meta-analysis to assess the diagnostic accuracy studies of IL-6 in diagnosing neonatal sepsis. Our results suggested that IL-6 is a valid and accurate index in diagnosing early neonatal sepsis, but it still needs to be combined with other laboratory tests and specific clinical manifestations.

Sufficient dimension reduction on the mean and rate functions of recurrent events.

The counting process with a Cox-type intensity function has been extensively applied to analyze recurrent event data, which assume that the underlying counting process is a time-transformed Poisson process and that the covariates have multiplicative or additive effects on the mean and rate functions of the counting process. The existing statistical inference, however, often encounters difficulties due to high-dimensional covariates, such as in gene expression and single nucleotide polymorphism data that have revolutionized our understanding of cancer recurrence and other diseases. In this paper, a technique of sufficient dimension reduction is applied to the mean and rate function for the number of occurrences of events over time. A two-step procedure is proposed to estimate the model components: first, a nonparametric estimator is proposed for the baseline, and then the basis of the central subspace and its dimension are estimated through a modified slicing inverse regression. On the basis of the estimated structural dimension and on the basis of the central subspace, we can estimate the regression function by using the local linear regression. A simulation is performed to confirm and assess the theoretical findings, and an application is demonstrated on a set of chronic granulomatous disease data.

The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration.

Both surface chemistry and topography have significant influence on good and fast osseointegration of biomedical implants; the main goals in orthopeadic, dental and maxillofacial surgeries. A surface modification strategy encompassing the use of bioactive trace elements together with surface micron/nano-topographical modifications was employed in this study in an attempt to enhance the osseointegration of Ti alloy (Ti-6Al-4V), a commonly used implant. Briefly, we developed strontium-substituted hardystonite (Sr-HT) ceramic coating with a hierarchical topography where the nanosized grains were superimposed in the micron-rough coating structure. Its ability to induce new bone formation was evaluated by an in vivo animal model (beagle dogs). Hardystonite (HT), classic hydroxyapatite (HAp) coated and uncoated Ti-alloy implants were parallelly investigated for comparison. In addition, we investigated the effects of surface topography and the dissolution products from the coatings on the in vitro bioactivity using canine bone marrow mesenchymal stem cells (BMMSCs) cultured on the implant surface as well as using extracts of the coated implants. Micro-CT evaluation, histological observations, biomechanical test (push-out test) and sequential fluorescent labeling and histomorphometrical analysis consistently demonstrated that our developed Sr-HT-coated Ti-alloy implants have the highest osseointegration, while the uncoated implants had the lowest. The osseointegration ability of HAp-coated Ti alloy was inferior to that seen for HT- and Sr-HT-coated Ti alloy. We demonstrated that the dissolution products, particularly strontium (Sr) from the Sr-HT-coated implants, enhanced the ALP activity and in vitro mineralization ability, while the micro/nano-topography was more related to the promotion of cell adhesion. Those results suggest that our developed Sr-HT coatings have the potential for future use as coatings for orthopedic/dental and maxillofacial devices.

Empirical receiver operating characteristic curve for two-sample comparison with cure fractions.

Two-sample comparison of survival times with "cured patients" is of major interest and a challenging issue in many areas, particularly in cancer clinical research. Recently, several authors have proposed various procedures of comparison, including tests of no overall, no short-term and no long-term differences between two samples. In clinical practice, it is often of interest to detect the difference in treatment effects among noncured patients regardless of the difference between cure fractions. In this paper, we propose a statistical test to compare two samples with cured patients and possibly heterogeneous treatment effects based on a class of semi-parametric transformation models, and our main focus is on the survival times of noncured patients. The empirical and quantile processes are used to construct strong approximations for the empirical curves. The two-sample test is then constructed from general least squares estimators derived from these processes. Simulation results show that the proposed test perform well. As an example of application, a set of bladder cancer data is analyzed to illustrate the proposed methods.

Discrete-time survival models with long-term survivors.

Discrete-time survival data typically possess three features: discreteness, ties, and concomitant information, which require appropriate discrete-time models to analyze. In this paper, we first review some existing discrete-time survival models and then extend them to discrete-time cure survival models, which account for the presence of long-term survivors (cured individuals). The maximum likelihood estimation as well as approximate partial likelihood approaches are used to estimate the model parameters. Simulation results are shown to support the suitability of such models for discrete-time survival data with long-term survivors. An example of applications on a set of bladder tumor recurrence data is also presented.