SCAN: Spatiotemporal Cloud Atlas for Neural cells.

The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.

Remodeling Microenvironment for Endogenous Repair through Precise Modulation of Chondroitin Sulfate Proteoglycans Following Spinal Cord Injury.

The fluid-filled cystic cavity sealed by a dense scar developed following traumatic spinal cord injury (SCI) has been a major obstacle to neural regeneration and functional recovery. Here the transected lesion is bridged using a functional self-assembling peptide (F-SAP) hydrogel loaded with membrane-permeable intracellular sigma peptide (ISP) and intracellular LAR peptide (ILP), targeted at perturbing chondroitin sulfate proteoglycan (CSPG) inhibitory signaling. As compared to F-SAP hydrogel loaded with chondroitinase ABC, the F-SAP+ISP/ILP promotes a beneficial anti-inflammatory response via manipulation of microglia/macrophages infiltration and assembly of extracellular matrix (ECM) molecules into fibrotic matrix rather than scarring tissues. The remodeled ECM creates a permissive environment that supports axon regrowth and the formation of synaptic connections with neurons derived from endogenous neural stem cells. The remodeled networks contribute to functional recovery, as demonstrated by improved hind limb movements and electrophysiological properties. This work proposes a unique mechanism that ECM remodeling induced by CSPG-manipulation-based anti-inflammation can construct a permissive environment for neural regeneration, and shed light on the advancement of manipulation of cascading cellular and molecular events potential for endogenous repair of SCI.

Effect of spinal-pelvic sagittal balance on the clinical outcomes after lumbar fusion surgery.

BACKGROUND: Spinal-pelvic sagittal balance is important for maintaining energy-efficient posture in normal and diseased states.Few reports to date have evaluated the effect of spinal-pelvic sagittal balance on clinical outcomes after lumbar interbody fusion in patients with lumbar degenerative diseases (LDD). METHODS: A total of 303 patients treated with posterior lumbar interbody fusion surgery for lumbar degenerative disease from January 2012 to December 2019 were enrolled in this retrospective study according to the inclusion criteria. Preoperative and postoperative spinal-pelvic sagittal parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL) of the patients were evaluated and compared. 163 patients whose postoperative PI-LL ≤ 10° were divided into the spinal-pelvic match group (Group M), while 140 patients were divided into the spinal-pelvic mismatch group (Group MM). Preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back pain of both groups were compared. RESULTS: There was no significant difference between the two groups in demographic and surgical data, except for blood loss in surgery. LL, PI, PT and SS of the patients at final follow-up were all statistically different from the preoperative values in the two groups(P < 0.05). There was no significant difference in LL, PI, PT and SS between the two groups before surgery. At the final follow-up, LL, PI and PT differed significantly between the two groups(P < 0.05). Compared with the preoperative results, ODI and VAS of low back in both groups decreased significantly at the final follow-up (P < 0.05). Significant differences in VAS and ODI were found between the two groups at the final follow-up (P < 0.05). The improvement rates of VAS and ODI of Group M are both significantly higher than Group MM. Regression analysis showed that age and spinal-pelvic match had significant effects on the improvement of patients' low back pain at the final follow-up. CONCLUSIONS: lumbar interbody fusion can significantly improve the prognosis of patients with LDD. In terms of outcomes with an average follow-up time of more than 2 years, the spinal-pelvic match has a positive effect on patients' quality of life and the release of low back pain.

Lumbar facet joint osteoarthritis as the underlying reason for persistent low back pain after minimally invasive discectomy.

INTRODUCTION: A post-hoc subgroup analysis of prospective collected data in a randomized controlled trial (RCT) of minimally invasive discectomy was conducted, to find out the possible underlying reasons for patients with persistent low back pain (LBP) following surgery. MATERIALS AND METHODS: Patients who were diagnosed with lumbar disc herniation (LDH) and underwent either percutaneous transforaminal endoscopic discectomy or microendoscopic discectomy in our RCT were analyzed. Patients with persistent LBP in 2-year follow-up were compared with the non-LBP patients to determine the underlying reasons. Then, the demographic characteristics, clinical outcomes and radiological parameters of patients with preoperative lumbar facet joint osteoarthritis (LFJOA) were assessed and compared with the non-LFJOA subgroup. RESULTS: 18 patients (8.1%) were reported to have persistent LBP in 2-year follow-up. Significantly higher proportion of preoperative LFJOA were found in the persistent LBP subgroup and was considered to be a risk factor using multivariate analysis. The prevalence of LFJOA is strongly associated with older age, female, high BMI and heavy labor in the LDH population. All of the clinical outcomes including ODI, SF36-PF, SF36-BP, EQ-5D, VAS-back and VAS-leg were worse in LFJOA subgroup in 2-year follow-up. LFJOA subgroup was associated with more adjacent segment degeneration and more lateral recess stenosis. CONCLUSIONS: LFJOA is a possible underlying reason for patients with persistent LBP after minimally invasive discectomy. Surgeons should carefully review the preoperative radiological images to find out whether there is LFJOA in the LDH segment, and kindly diminish the expectation of back pain relief for those patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov at November 14, 2013, registration number NCT01997086. ( https://clinicaltrials.gov/ct2/show/NCT01997086 ).

Modified low-bandwidth sub-Nyquist sampling receiving scheme in an IM/DD OFDM system enabled by improved optical shaping.

In this paper, a modified low-bandwidth sub-Nyquist sampling receiving scheme enabled by optical shaping is investigated in an intensity modulation/direct detection (IM/DD) orthogonal frequency-division multiplexing (OFDM) system, which can reduce the sampling rate and analog bandwidth of an analog-to-digital converter (ADC) at the receiving end. By changing the phase matrix of preprocessing, the modified scheme can distinguish different groups of data only by controlling the delay of the shaping module. In addition, the proposed RF sharing architecture can further reduce the cost and increase the feasibility of the scheme. Based on arcsine digital pre-distortion (DPD) technology, a DPD optical pulse shaping scheme is proposed to achieve better spectrum aliasing in the optical domain. With the help of the DPD shaping, we successfully experimentally demonstrate the 12.5-GHz/44.45-Gbit/s IM/DD OFDM system with low-bandwidth (3.125 GHz) and sub-Nyquist sampling rate (6.25 GSa/s) ADC. The experiment results show that the proposed scheme can not only effectively achieve low-bandwidth reception, but also achieve about 0.4 dB receiver sensitivity improvement compared with the traditional high-bandwidth scheme at BER of 3.8×10-3 after 10.2 km standard single mode fiber transmission, which indicates that the proposed scheme is a promising low-cost candidate to provide large transmission capacity for the next-generation network.

A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/mL at initial biopsy.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Ion-Conductive Hydrogel-Based Stretchable, Self-Healing, and Transparent NO2 Sensor with High Sensitivity and Selectivity at Room Temperature.

Here stretchable, self-healable, and transparent gas sensors based on salt-infiltrated hydrogels for high-performance NO2 sensing in both anaerobic environment and air at room temperature, are reported. The salt-infiltrated hydrogel displays high sensitivity to NO2 (119.9%/ppm), short response and recovery time (29.8 and 41.0 s, respectively), good linearity, low theoretical limit of detection (LOD) of 86 ppt, high selectivity, stability, and conductivity. A new gas sensing mechanism based on redox reactions occurring at the electrode-hydrogel interface is proposed to understand the sensing behaviors. The gas sensing performance of hydrogel is greatly improved by incorporating calcium chloride (CaCl2 ) in the hydrogel via a facile salt-infiltration strategy, leading to a higher sensitivity (2.32 times) and much lower LOD (0.06 times). Notably, both the gas sensing ability, conductivity, and mechanical deformability of hydrogels are readily self-healable after cutting off and reconnection. Such large deformations as 100% strain do not deprive the gas sensing capability, but rather shorten the response and recovery time significantly. The CaCl2 -infiltrated hydrogel shows excellent selectivity of NO2 , with good immunity to the interference gases. These results indicate that the salt-infiltrated hydrogel has great potential for wearable electronics equipped with gas sensing capability in both anaerobic and aerobic environments.

Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.

BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.

Amyloid ß peptide promotes bone formation by regulating Wnt/ß-catenin signaling and the OPG/RANKL/RANK system.

BACKGROUND: Amyloid ß peptide (Aß) is involved in osteoporosis, but the effects of Aß on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aß on bone formation. METHODS: An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aß. The effect of Aß on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. RESULTS: In the animal study, intraperitoneal injection of Aß for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aß treatment significantly elevated osterix+ (osteoblastic) cells but decreased TRAP+ cells (osteoclasts) in the distal femur bone. In vitro study showed that Aß treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aß treatment activated Wnt/ß-catenin signaling in hBMSCs. The effect of Aß was blocked by DKK1 (a Wnt/ß-catenin inhibitor) treatment. In the co-culture system, Aß treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP+ RAW264.7 cells (pre-osteoclasts). Aß treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aß treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). CONCLUSION: Aß treatment simultaneously promoted osteogenic differentiation via Wnt/ß-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aß is a positive regulator of osteoblast differentiation and bone formation.

Casein kinase 1 epsilon facilitates cartilage destruction in osteoarthritis through JNK pathway.

Osteoarthritis (OA) is a high-morbidity skeletal disease worldwide and the exact mechanisms underlying OA pathogenesis are not fully understood. Casein kinase 1 epsilon (CK1ε) is a serine/threonine protein kinase, but its relationship with OA is still unknown. We demonstrated that CK1ε was upregulated in articular cartilage of human patients with OA and mice with experimentally induced OA. Activity of CK1ε, demonstrated by analysis of phosphorylated substrates, was significantly elevated in interleukin (IL)-1ß-induced OA-mimicking chondrocytes. CK1ε inhibitor or CK1ε short hairpin RNA (shRNA) partially blocked matrix metalloproteinase (MMP) expression by primary chondrocytes induced by IL-1ß, and also inhibited cartilage destruction in knee joints of experimental OA model mice. Conversely, overexpression of CK1ε promoted chondrocyte catabolism. Previous studies indicated that CK1ε was involved in canonical Wnt/ß-catenin signaling and noncanonical Wnt/c-Jun N-terminal kinase (JNK) signaling pathway. Interestingly, the activity of JNK but not ß-catenin decreased after CK1ε knockdown in IL-1ß-treated chondrocytes in vitro, and JNK inhibition reduced MMP expression in chondrocytes overexpressing CK1ε, which illustrated that CK1ε-mediated OA was based on JNK pathway. In conclusion, our results demonstrate that CK1ε promotes OA development, and inhibition of CK1ε could be a potential strategy for OA treatment in the future.

Subarachnoid transplantation of human umbilical cord mesenchymal stem cell in rodent model with subacute incomplete spinal cord injury: Preclinical safety and efficacy study.

Functional multipotency renders human umbilical cord mesenchymal stem cell (hUC-MSC) a promising candidate for the treatment of spinal cord injury (SCI). However, its safety and efficacy have not been fully understood for clinical translation. In this study, we performed cellular, kinematic, physiological, and anatomical analyses, either in vitro or in vivo, to comprehensively evaluate the safety and efficacy associated with subarachnoid transplantation of hUC-MSCs in rats with subacute incomplete SCI. Concerning safety, hUC-MSCs were shown to have normal morphology, excellent viability, steady proliferation, typical biomarkers, stable karyotype in vitro, and no tumorigenicity both in vitro and in vivo. Following subarachnoid transplantation of hUC-MSCs in the subject rodents, the biodistribution of hUC-MSCs was restricted to the spinal cord, and no toxicity to immune system or organ function was observed. Body weight, organ weight, and the ratio of the latter upon the former between stem cell-transplanted rats and placebo-injected rats revealed no statistical differences. Regarding efficacy, hUC-MSCs could differentiate into osteoblasts, chondrocytes, adipocytes and neural progenitor cells in vitro. While in vivo studies revealed that subarachnoid transplantation of stem cells resulted in significant improvement in locomotion, earlier automatic micturition recovery and reduced lesion size, which correlated with increased regeneration of tracking fiber and reduced parenchymal inflammation. In vivo luminescence imaging showed that a few of the transplanted luciferase-labeled hUC-MSCs tended to migrate towards the lesion epicenter. Shortened latency and enhanced amplitude were also observed in both motor and sensory evoked potentials, indicating improved signal conduction in the damaged site. Immunofluorescent staining confirmed that a few of the administrated hUC-MSCs integrated into the spinal cord parenchyma and differentiated into astrocytes and oligodendrocytes, but not neurons. Moreover, decreased astrogliosis, increased remyelination, and neuron regeneration could be observed. To the best of our knowledge, this preclinical study provides detailed safety and efficacy evidence regarding intrathecal transplantation of hUC-MSCs in treating SCI for the first time and thus, supports its initiation in the following clinical trial.

CD39 Produced from Human GMSCs Regulates the Balance of Osteoclasts and Osteoblasts through the Wnt/ß-Catenin Pathway in Osteoporosis.

Osteoporosis is a disease in which the density and quality of bone are reduced, causing bones to become weak and so brittle that a fall or even mild stresses can cause a fracture. Current drug treatment consists mainly of antiresorptive agents that are unable to stimulate new bone formation. Our recent studies have defined a critical role of gingiva-derived mesenchymal stem cells (GMSCs) in attenuating autoimmune arthritis through inhibition of osteoclast formation and activities, but it remains to be ruled out whether the administration of GMSCs to patients with osteoporosis could also regulate osteoblasts and eventually affect bone formation and protection. With the use of an ovariectomized mouse model, we here demonstrated that adoptive transfer of GMSCs regulated the balance of osteoclasts and osteoblasts, eventually contributing to dynamic bone formation. Validation by RNA sequencing (RNA-seq), single-cell sequencing, revealed a unique population of CD39+ GMSC that plays an important role in promoting bone formation. We further demonstrated that CD39 produced from GMSC exerted its osteogenic capacity through the Wnt/ß-catenin pathway. Our results not only establish a previously unidentified role and mechanism of GMSC for bone promotion but also a potential therapeutic target for management of patients with osteoporosis and other bone loss conditions.

Free vitamin D correlate better with bone mineral density and thoracolumbar junction osteoporotic vertebral fractures than serum vitamin D.

BACKGROUND: Vitamin D deficiency has long been studied as a risk factor for osteoporosis. However, the association between serum vitamin D status, bone mineral density (BMD) and the incidence of vertebral fractures (OVFs) remain controversial. It is believed that free portion of the circulating vitamin D carries the metabolic activities of vitamin D. Therefore, the aim of the present study is to analyse if free vitamin D correlates with BMD and osteoporotic fragile vertebral fractures in the elderly population. METHODS: A total of 90 consecutive patients, including 81 female and 9 male patients, aged > 48 years, were included in this cross sectional study between March and July of 2018. Total vitamin D (total 25(OH)D), free vitamin D (free 25(OH)D), calcium and phosphorus were measured. BMD was measured using dual energy X-ray absorptiometry (DEXA) and osteoporotic vertebral fracture was assessed using plain radiograph. Multiple linear regression was performed to find out the association between total vitamin D, free vitamin D and BMD at various sites. To evaluate the association with osteoporotic vertebral multivariate logistic regression model was used. RESULTS: The mean total vitamin D and free vitamin D were 25.1 ± 10.2 and 6.1 ± 1.7 respectively. Free vitamin D had a linear correlation with total vitamin D (R2 = 0.69). While free vitamin D had a positive correlation with lumbar BMD roles (p < 0.05), total vitamin D didn't have any association with BMD at any site. Of the total patients, 62 patients (68.9%) had thoracolumbar junction OVFs. Free vitamin D level correlated with the prevalence of OVFs as well as lumbar osteoporosis (p < 0.05). However, there was no statistical correlation between serum vitamin D status and the OVFs. CONCLUSIONS: Free vitamin D was significantly related to the occurrence of thoracolumbar junction OVFs and lumbar BMD, which assumed to be a positive predictor for fracture and osteoporosis prevention. However, total serum vitamin D levels did not have any association with BMD at different sites as well as fragile vertebral fracture. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov NCT03605173.

Percutaneous transforaminal full endoscopic decompression for the treatment of lumbar spinal stenosis.

BACKGROUND: One advantage of an endoscopic approach to treating lumbar spinal stenosis is preservation of spine stability and the adjacent anatomy, and there is a decrease in adjacent segment disc degeneration. The purpose of this study was to discuss the clinical efficacy of percutaneous transforaminal endoscopic decompression for the treatment of lumbar spinal stenosis (LSS). METHODS: This is a retrospective study. From September 2012 to June 2017, 45 patients who were diagnosed with LSS underwent the treatment of percutaneous transforaminal endoscopic decompression (PTED) and were followed up at 1 week, 3 months and 1 year postoperatively. Low back pain and leg pain were measured by Visual Analogue Scale scoring methods (VAS-back and VAS-leg), while functional outcomes were assessed by using the Oswestry Disability Index (ODI). All patients had one-level lumbar spinal stenosis. RESULTS: The most common type of stenosis was lateral recess stenosis (n = 22; 48.9%), followed by central stenosis (n = 13; 28.9%) and foraminal stenosis (n = 10: 22.2%). Regarding comparisons of VAS-back, VAS-leg, and ODI scores before and after operation, VAS and ODI scores significantly improved. The average leg VAS score improved from 7.01 ± 0.84 to 2.28 ± 1.43 (P < 0.001). The average ODI improved from 46.18 ± 10.11 to 14.40 ± 9.59 (P < 0.001). We also examined changes in ODI and VAS scores from baseline according to types of spinal stenosis, stenosis grade, spinal instability, and revision surgery in the same segment. The improvement percentage of leg VAS score was significantly less in patients with severe stenosis at both 3 months and 1 year postoperatively. The improvement percentages of ODI and leg VAS scores were significantly less in patients who had spinal instability and patients who had undergone revision surgery. CONCLUSION: The PTED approach seems to give good results for the treatment of LSS. However, this approach may be less effective for LSS patients who have lumbar instability or require revision surgery in the same segment.

[Analysis of a female with a peripheral blood lymphocytic karyotype of trisomy 18 but normal intelligence].

OBJECTIVE: To explore the genetic basis for a female with a peripheral lymphocyte karyotype of trisomy 18 but normal intelligence. METHODS: G-banding karyotype analysis, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism microarray (SNP array) were employed to analyze the peripheral blood sample and buccal cells from the patient. RESULTS: Chromosomal karyotyping, SNP array and FISH analysis of the patient's peripheral blood all suggested 47,XX,+18. Interphase FISH analysis of buccal cells, however, revealed presence of 45,X and low percentage of trisomy 18 and monosomy 18. CONCLUSION: The clinical manifestation of germ layer chromosomal mosaicism is complex. The impact of the genetic disorder on the individual will depend on the structure and function derived from the affected germ layer.

Long noncoding RNA UCA1 promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells via miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis.

Long noncoding RNA (lncRNAs) UCA1 has been known to be critical for the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). In this study, we explore the effects and mechanisms of UCA1 on the promotion of chondrogenesis of MSCs. During the processes of chondrogenic differentiation of MSCs, UCA1, miRNA-145-5p or miRNA-124-3p was overexpressed into MSCs. UCA1 substantially improved chondrogenesis of MSCs. Furthermore, UCA1 obviously down-regulated the expression of miRNA-145-5p and miRNA-124-3p, which attenuated the chondrogenic differentiation of MSCs. In addition, UCA1 significantly stimulated TGF-ß pathway member SMAD5 and SMAD4, which is targeted by miRNA-145-5p and miRNA-124-3p. Collectively, these outcomes suggest that UCA1 enhances chondrogenic differentiation of MSCs via the miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis.

Vitamin D Deficiency/Insufficiency Is Associated with Risk of Osteoporotic Thoracolumbar Junction Vertebral Fractures.

BACKGROUND The association between serum vitamin D level and vertebral fracture (VFx) remains controversial. The purpose of this study was to determine whether serum 25-hydroxy vitamin D (25(OH)D) level is associated with osteoporotic thoracolumbar junction VFx in elderly patients. MATERIAL AND METHODS From Jan 2013 to Dec 2017, this retrospective case-control study included 534 patients with primary osteoporotic thoracolumbar junction VFx (T10-L2) and 569 elderly orthopedic patients with back pain (without osteoporotic VFx) as controls. Serum 25(OH)D levels were measured and the association with osteoporotic VFx was analyzed. Other clinical data, including BMI, comorbidities, and bone mineral density (BMD), were also collected and compared between these 2 groups. RESULTS It was shown that 25(OH)D levels were significantly lower in patients with T10-L2 VFx than in control patients. Among 534 VFx patients, 417 (78.1%) patients showed grade 2-3 fracture. Serum 25(OH)D levels were significantly related to affected vertebral numbers and VFx severities. The VFx risk was 28% lower (OR=0.72, 95% CI 0.62-0.83) per increased SD in serum 25(OH)D. Compared with the 1st quartile (mean 25(OH)D: 29.67±6.18 nmol/L), the VFx risk was significantly lower in the 3rd (mean 25(OH)D: 60.91±5.12nmol/L) and 4th quartiles (mean 25(OH)D: 103.3±44.21nmol/L), but not in the 2nd quartile (mean 25(OH)D: 45.40±3.95 nmol/L). In contrast, the VFx risk was significantly increased in the 1st quartile (OR=1.87, 95% CI 1.42-2.45) compared with the 2nd-4th quartiles. CONCLUSIONS Vitamin D deficiency/insufficiency was associated with risk of osteoporotic thoracolumbar junction vertebral fractures in elderly patients.

A meta-analysis of serum osteocalcin level in postmenopausal osteoporotic women compared to controls.

BACKGROUND: Circulatory osteocalcin (OC) has been widely used as a biomarker to indicate bone turnover status in postmenopausal osteoporosis (PMO). However, the change of serum OC (sOC) level in PMO cases compared to postmenopausal controls remains controversial. METHODS: We searched the online database of PubMed and Cochrane Library. A meta-analysis of case-control studies was performed to compare the pooled sOC level between PMO patients and postmenopausal controls. Subgroup analysis according to potential confounding factors (different OC molecules and regions of the study population) was also performed. RESULTS: Ten case-control studies with 1577 postmenopausal women were included in this meta analysis. We found no significant difference in the pooled sOC level [mean difference (MD) = 1.84, 95% confidence interval (CI): (- 1.49, 5.16), p = 0.28] between PMO patients and controls. Subgroup analysis also revealed no significant difference in intact OC [MD = 1.76, 95%CI: (- 1.71, 5.23), p = 0.32] or N-terminal mid-fragment of the OC molecule [MD = 0.67, 95%(- 5.83, 7.18), p = 0.84] between groups. For different regions, no significant difference in sOC was found in Asian population between cases and controls [MD = -0.06, 95%(- 6.02, 5.89), p = 0.98], while the pooled sOC level was significantly higher in European PMO cases than controls [MD = 3.15, 95%(0.90, 5.39), p = 0.006]. CONCLUSIONS: Our analysis revealed no significant difference in sOC level between PMO cases and controls according to all the current eligible studies. OC molecules are quite heterogeneous in the circulation and can be influenced by glucose metabolism. Therefore, sOC is currently not a good indicator for the high bone turnover status in PMO. More trials with standardized methodologies for the evaluation of circulatory OC are awaited to update our current findings.

[Correlation of thickened nuchal fold with fetal chromosomal abnormalities among 919 cases].

OBJECTIVE: To explore the correlation between fetal nuchal fold (NF) thickening and fetal chromosomal abnormality. METHODS: In total 919 pregnant women undergoing ultrasound examination were selected for interventional prenatal diagnosis in order to detect fetal chromosomal abnormality. RESULTS: The detection rate of chromosomal abnormality has significantly increased with NF thickness, advanced maternal age, presence of other ultrasound abnormalities (P<0.05). Trisomy 21 was the most common abnormality, and there was a prepondance for male fetuses. CONCLUSION: Increased NF thickness is strongly associated with the risk of fetal chromosomal abnormalities, advanced maternal age and presence of additional ultrasound abnormalities.

Melatonin-mediated miR-526b-3p and miR-590-5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (BMSCs), with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. Accumulating evidence has demonstrated that melatonin can promote chondrogenic differentiation in human BMSCs. However, little is known about the mechanism. MicroRNAs (miRNAs) have been shown to regulate the differentiation of BMSCs, but their roles in melatonin-promoted chondrogenic differentiation have not been characterized. Here, we demonstrate that melatonin promoted chondrogenic differentiation of human BMSCs via upregulation of miR-526b-3p and miR-590-5p. Mechanistically, the elevated miR-526b-3p and miR-590-5p enhanced SMAD1 phosphorylation by targeting SMAD7. Additionally, administration of miR-526b-3p mimics or miR-590-5p mimics successfully promoted the chondrogenic differentiation of human BMSCs. Collectively, our study suggests that modification of BMSCs using melatonin or miRNA transduction could be an effective therapy for cartilage damage and degeneration.