Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disk Herniation: Five-year Results of a Randomized Controlled Trial.

STUDY DESIGN: A prospective randomized controlled study. OBJECTIVE: To compare the efficacy and safety between percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED). SUMMARY OF BACKGROUND DATA: Two kinds of minimally invasive discectomy, PTED and MED, are now widely used for treating lumbar disk herniation (LDH). The long-term comparative results of these two techniques still remained uncertain. MATERIALS AND METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH and were randomly allocated to PTED or MED groups. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain (SF36-BP) and physical function (SF36-PF), European Quality of Life-Five Dimensions (EQ-5D), Visual Analog Scales for back pain (VAS-back) and leg pain (VAS-leg). RESULTS: A total of 241 patients were accepted to enroll in our randomized controlled trial, of which 119 were randomly assigned to the PTED group, and the rest 122 were assigned to the MED group. A total of 194 out of 241 patients (80.5%) completed the five-year follow-up. PTED group was associated with shorter postoperative in-bed time and length of hospital stay. Both primary and secondary outcomes did not differ significantly between the two treatment groups at each follow-up time point. During the five-year follow-up, seven recurrent cases occurred in PTED and MED groups, respectively. CONCLUSION: Over the five-year follow-up period, PTED and MED were both efficacious in the treatment of LDH. The long-term clinical outcomes and recurrent rates were comparable between the treatment groups. PTED represents a more minimally invasive technique with the advantages of rapid recovery.

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 ).

CHESS endoscopic ruler in objective measurement of diameter of esophageal varices in liver cirrhosis and portal hypertension: a prospective multicenter study / 中华消化杂志

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Study on improvement mechanism of caudatin on liver injury in rats / 中国药房

OBJECTIVE To investigate the improvement mechanism of caudatin on liver injury of rats. METHODS SD rats were randomly divided into blank group， model group， caudatin low-dose and high-dose groups （25， 50 mg/kg）， with 6 rats in each group. Diethylnitrosamine （DEN） was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling， the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total protein （TP） and total bilirubin （TBI）] and inflammatory factors [interleukin （IL-6）， tumor necrosis factor α （TNF-α）， IL-1β] in serum were detected； the histopathological morphological changes of rat liver were observed； the positive protein expressions of nuclear factor κB （NF-κB） and 78 kDa glucose regulatory protein （Grp78） in liver tissue were also determined； the expressions of endoplasmic reticulum stress-related protein Grp78， C/EBP homologous protein （CHOP）， activating transcription factor 6 （ATF6） and inositol requiring enzyme 1α （IRE1α） and the level of protein kinase R-like endoplasmic reticulum kinase robertluoyi@126.com （PERK） in liver tissue were detected. RESULTS Compared with blank group， serum levels of ALT， AST， TBI， IL-6， TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78， CHOP， ATF6 and IRE1α， PERK protein phosphorylation level were all increased significantly in model group （P＜0.05）， while the serum level of TP was decreased significantly （P＜0.05）. The disordered structure of liver lobule， swollen liver cells， unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group， most of the above indexes were significantly reversed in caudatin groups （P＜0.05）； the structure of hepatic lobule was relatively complete and clear， the cells were arranged orderly， and the infiltration of inflammatory cells was also reduced. CONCLUSIONS Caudatin has a significant improvement effect against DEN-induced liver injury in rats， the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.

Melatonin contributes to the hypertrophic differentiation of mesenchymal stem cell-derived chondrocytes via activation of the Wnt/ß-catenin signaling pathway : Melatonin promotes MSC-derived chondrocytes hypertrophy.

BACKGROUND: Hypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis. However, little is known about the effects of melatonin on the terminal differentiation of chondrocytes. METHODS: Mesenchymal stem cell (MSC)-derived chondrocytes generated by a high-density micromass culture system were induced to undergo hypertrophic differentiation. Melatonin-mediated hypertrophic differentiation was examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis, histological staining and immunohistochemistry. Activation of the Wnt signaling pathway was evaluated by PCR array, RT-PCR, western blotting and immunofluorescence. XAV-939, a Wnt signaling pathway antagonist, was further used to determine whether the effect of melatonin on chondrocyte hypertrophic differentiation was mediated occurred by activation of Wnt signaling pathway. RESULTS: Histological staining showed melatonin increased chondrocyte cell volume and the expression of type X collagen but decreased the expression of type II collagen compared with the control group. RT-PCR showed that melatonin significantly up-regulated the gene expressions of biomarkers of hypertrophic chondrocytes, including type X collagen, alkaline phosphatase, runt-related transcription factor 2, Indian hedgehog and parathyroid hormone-related protein receptor, and melatonin down-regulated the mRNA expression of hallmarks of chondrocytes, including parathyroid hormone-related protein. PCR array showed that the effect of melatonin on chondrocyte hypertrophic differentiation was accompanied by the up-regulation of multiple target genes of the canonical Wnt signaling pathway, and this effect was blocked by XAV-939. CONCLUSIONS: The current findings demonstrate that melatonin enhances the hypertrophic differentiation of MSC-derived chondrocytes through the Wnt signaling pathway. Our findings add evidence to the role of melatonin in promoting bone development and highlight the positive effects of melatonin on terminal differentiation of chondrocytes.

Identification of HCG18 and MCM3AP-AS1 That Associate With Bone Metastasis, Poor Prognosis and Increased Abundance of M2 Macrophage Infiltration in Prostate Cancer.

BACKGROUND: Bone metastasis is a leading cause of the high mortality rate of prostate cancer (PCa), but curative strategies remain lacking. Recent studies suggest long non-coding RNAs (lncRNAs) may be potential targets to develop drugs. However, PCa bone metastasis-specifically-related lncRNAs were rarely reported. This study aimed to identify crucial lncRNAs and reveal their function mechanisms. METHODS: GSE32269 and GSE26964 microarray datasets, downloaded from the Gene Expression Omnibus database, were used to analyze differentially expressed genes (DEGs)/lncRNAs (DELs) and miRNAs (DEMs), respectively. Weighted gene co-expression network analysis was performed to screen PCa bone metastasis-associated modules. The co-expression and competing endogenous RNAs (ceRNAs) networks were constructed to identify hub lncRNAs. Univariate Cox regression analysis was conducted to determine their prognostic values. The correlation of lncRNAs with immune infiltrating cells was analyzed by using Tumor IMmune Estimation Resource. Therapeutic drugs were predicted by querying the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 18 DELs, 2,614 DEGs and 86 DEMs were screened between bone metastatic and primary PCa samples. Four modules enriched by DEGs were shown to be bone metastasis-associated. LncRNA HCG18 and MCM3AP-AS1 were identified to be important because they existed in both of the co-expression and ceRNA networks (forming the relationship pairs: HCG18/MCM3AP-AS1-KNTC1, MCM3AP-AS1-hsa-miR-508-3p-DTL and HCG18/MCM3AP-AS1-hsa-miR-127-3p-CDKN3). All the genes in these interaction pairs were significantly associated with overall survival of PCa patients. Also, HCG18, MCM3AP-AS1 and their target mRNAs were positively correlated with various tumor-infiltrated immune cells, especially increased M2 macrophages. Valproic acid and trichostatin A may be effective to treat PCa bone metastasis by targeting HCG18 and MCM3AP-AS1. CONCLUSION: HCG18 and MCM3AP-AS1 that regulate M2 macrophage infiltration may be important targets to treat PCa bone metastasis and improve prognosis.

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.

Anterior cervical discectomy and fusion versus posterior cervical foraminotomy for the treatment of single-level unilateral cervical radiculopathy: a meta-analysis.

BACKGROUND: To compare the effectiveness and safety of anterior cervical discectomy and fusion (ACDF) with posterior cervical foraminotomy (PCF) for patients diagnosed with single-level unilateral cervical radiculopathy. METHODS: Relevant studies comparing ACDF with PCF for cervical radiculopathy were searched in an electronic database. After data extraction and quality assessment of included studies, a meta-analysis was done by using the RevMan 5.3 software. The random effects model was used if there was heterogeneity between studies; otherwise, the fixed effects model was used. RESULTS: A total of 3 randomized controlled trials (RCT) and 12 retrospective studies including 52705 patients were included in the meta-analysis. There were no significant differences in Neck Disability Index (NDI), Visual Analog Scale (VAS), and patients' satisfaction (P > 0.05) between treatment groups. The complication rate of the PCF group was equivalent compared with the ACDF group (P = 0.60), but the reoperation rate following PCF was on the higher side (P = 0.02). Data analysis also showed that the PCF group was associated with shorter operation time (P = 0.001) and shorter length of hospital stay (P = 0.002). CONCLUSIONS: Among patients with single-level unilateral cervical radiculopathy, PCF has comparable effectiveness and complication rate compared with ACDF. It seems that PCF is a sufficient alternative procedure with shorter operation time, shorter length of hospital stay, and less total hospital cost for the treatment of cervical radiculopathy. However, the higher reoperation rate following PCF should be also taken into consideration.

Melatonin Promotes Neuroprotection of H2O2-induced Neural Stem Cells via lncRNA MEG3/miRNA-27a-3p/MAP2K4 axis.

Melatonin is crucial for protecting neural stem cells (NSCs) from reactive oxygen species (ROS). However, the mechanism underlying these processes is unclear. In this study, we first investigated the significantly upregulated lncRNA MEG3 biomarker in the H2O2-induced NSCs and control groups. Melatonin inhibited the expression of MEG3 by methylation. MEG3 overexpression reversed the positive effects of melatonin on NSCs against H2O2. Furthermore, MEG3 reduced the expression levels of its targeted miRNA-27a-3p, which could be considered a neuroprotective effect. In addition, the elevated miRNA-27a-3p decreased JNK phosphorylation by targeting MAP2K4. Overexpression of MAP2K4 suppressed the neuroprotective effects of miRNA-27a-3p. Therefore, melatonin appeared to protect NSCs from H2O2-induced ROS by modification of the MEG3/miRNA-27a-3p/MAP2K4 axis.

Exosomes derived from miRNA-210 overexpressing bone marrow mesenchymal stem cells protect lipopolysaccharide induced chondrocytes injury via the NF-κB pathway.

Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exos) have anti-inflammatory and anti-apoptotic functions. miRNA-210 has also been confirmed to play a role in inhibiting proinflammatory cytokines. Herein, we aimed to explore the effects of Exos derived from miRNA-210-overexpressing BMSCs (BMSCs-210-Exos) and the mechanisms by which they provide protection to chondrocytes from lipopolysaccharide (LPS)-induced injury. BMSCs were transfected with or without miRNA-210. Exos substantially improved the proliferation of chondrocytes and inhibited LPS-induced cell apoptosis. Furthermore, BMSCs-210-Exos promoted the proliferation of chondrocytes and prevented LPS-induced cell apoptosis better than BMSCs-Exos not overexpressing miRNA-210. In addition, tumor necrosis factor receptor superfamily member 21 (Tnfrsf21) expression was inhibited and the NF-κB pathway was attenuated by both BMSCs-Exos and BMSCs-210-Exos during LPS-induced chondrocyte injury. Collectively, these results suggest that BMSCs-210-Exos enhance the protection of chondrocytes from LPS-induced injury via the NF-κB pathway.

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.

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.

Percutaneous Transforaminal Endoscopic Discectomy Versus Microendoscopic Discectomy for Lumbar Disc Herniation: Two-Year Results of a Randomized Controlled Trial.

STUDY DESIGN: A prospective randomized controlled study. OBJECTIVE: To clarify whether percutaneous transforaminal endoscopic discectomy (PTED) has better clinical outcomes and less surgical trauma compared with microendoscopic discectomy (MED). SUMMARY OF BACKGROUND DATA: Two kinds of minimally invasive spine surgeries, PTED and MED, are now widely used for the treatment of lumbar disc herniation (LDH). It is still a controversial issue to choose the proper surgical approach. METHODS: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH, and were randomly allocated to PTED or MED group. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, European Quality of Life-5 Dimensions, and Visual Analogue Scales for back pain and leg pain. RESULTS: A total of 250 participants were randomly assigned to two treatment groups, 241 of that received the specific surgical procedure. Two hundred twenty-two patients (92.1%) have completed the 2-year follow-up. Both the primary and secondary outcomes did not differ significantly between the two treatment groups at each prespecified follow-up time (P > 0.05). For PTED, the postoperative improvement of ODI score in the median herniation subgroup was less compared with paramedian subgroup. For MED, less improvement of ODI score was found in far-lateral herniation subgroup compared with paramedian subgroup. Total complication rate over the course of 2 year was 13.44% in PTED group and 15.57% in MED group (P = 0.639). Ten cases (8.40%) in PTED group and five cases (4.10%) in MED group suffered from residue/recurrence of herniation, for which reoperation was required. CONCLUSION: Over the 2-year follow-up period, PTED did not show superior clinical outcomes and did not appear to be safer procedure for patients with LDH compared with MED. PTED had inferior results for median disc herniation, whereas MED did not appear to be the best option for far-lateral disc herniation. LEVEL OF EVIDENCE: 2.

Surgery vs conservative treatment for type II and III odontoid fractures in a geriatric population: A meta-analysis.

BACKGROUND: It is unclear whether surgery or conservative treatment is more suitable for elderly patients with type II and type III odontoid fractures. We performed this meta-analysis to compare the efficacy of surgical and conservative treatments for type II and type III odontoid fractures. METHODS: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library in January 2017. Only articles comparing surgery with conservative treatment in elderly patients with type II and type III odontoid fractures were selected. After 2 authors independently assessed the retrieved studies, 18 articles were included in this meta-analysis, and the primary endpoints were the nonunion rate and mortality rate. The secondary outcomes were patient satisfaction, complications, and the length of the hospital stay. The quality of the included studies was evaluated using the modified Newcastle-Ottawa scale. Sensitivity analyses were performed for high-quality studies, and the publication bias was evaluated using a funnel plot. RESULTS: Lower nonunion (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.18-0.40, P < .05) and mortality rates (OR: 0.52, 95% CI: 0.34-0.79, P < .05) confirmed the superiority of surgery in treating type II and type III fractures. The secondary outcomes differed. Patients in the surgery group felt more satisfied with the outcome (OR: 3.44, 95% CI: 1.19-9.95, P < .05), and the complications were similar in the 2 groups (OR: 1.14, 95% CI: 0.78-1.68, P = .5), whereas patients in conservative groups spent less time in the hospital (OR: 5.10, 95% CI: 2.73-7.47, P < .05). The results of the subgroup analyses and sensitivity analysis were similar to the original outcomes, and no obvious publication bias was observed in the funnel plot. CONCLUSION: Most elderly (younger than 70 years) patients with type II or type III odontoid fractures should be considered candidates for surgical treatment, due to the higher union rate and lower mortality rate, while statistically significant differences were not observed in the population with an advanced age (older than 70 years). Therefore, the selection of the therapeutic approach for elderly patients with odontoid fractures requires further exploration. Simultaneously, based on our meta-analysis, a posterior arthrodesis treatment was significantly superior to the anterior odontoid screw treatment.

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.

Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study.

PURPOSE: Blood vessels and skeleton interact together. Endothelin-1 is a potent vasoconstrictor and also has an effect on bone metabolism. The dual antagonist to both endothelin-1 type A and B receptors, Macitentan, has been approved for clinical management of pulmonary arterial hypertension while little is known about the secondary effect of the drug on spine. We aimed to answer how vertebral bone mass responded to Macitentan treatment in mice. METHODS: Sixteen male balb/c mice at 6 months were randomly assigned into 2 groups. Vehicle and Macitentan were administrated via intraperitoneal injection to Control group and Treatment group, respectively, for 4 months. At sacrifice, plasma endothelin-1 was evaluated with ELISA and vertebral bone mass was evaluated with Microcomputed Tomography and histological analysis. RESULTS: We found higher plasma endothelin-1 level (p<0.01) and less vertebral bone mass (p<0.05) in Treatment group compared to controls. Moreover, less osteoblasts and more osteoclasts were observed in the vertebral trabecular bone in the Treatment group compared to controls, by immunohistochemistry of the cell-specific markers. CONCLUSIONS: Treatment with Macitentan is associated with significant lower vertebral bone mass and therefore the secondary effect of dual antagonists to endothelin-1 receptors on the skeleton should be monitored and investigated in clinical practice. Both osteoblasts and osteoclasts may be involved while the molecular mechanism needs to be further explored.

Salvianolic acid B promotes neural differentiation of induced pluripotent stem cells via PI3K/AKT/GSK3ß/ß-catenin pathway.

Salvianolic acid B (Sal B), a water-soluble component mainly extracted from the traditional Chinese medicine Salvia miltiorrhiza, has potential anti-inflammatory, anti-oxidative and anti-apoptotic actions to protect neural cells. Here, we explore the effects and mechanisms of Sal B on the promotion of differentiation of induced pluripotent stem cells (iPSCs) into neural stem cells (NSCs), then further into neurons. During the processes of neural differentiation of iPSCs, Sal B or a phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002) were added to the medium. Sal B substantially improved proliferation of iPSC-derived NSCs and neurons. Furthermore, Sal B significantly stimulated PI3K/AKT/GSK3 ß/ß-catenin pathway. However, LY294002 attenuated the Sal B-induced increase. Therefore, these outcomes suggest that Sal B markedly enhances neural differentiation of iPSCs via the PI3K/AKT/GSK3ß/ß-catenin pathway.

Percutaneous transforaminal endoscopic discectomy compared with microendoscopic discectomy for lumbar disc herniation: 1-year results of an ongoing randomized controlled trial.

OBJECTIVE A prospective randomized controlled study was conducted to clarify whether percutaneous transforaminal endoscopic discectomy (PTED) results in better clinical outcomes and less surgical trauma than microendoscopic discectomy (MED). METHODS In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed lumbar disc herniation. Patients were randomly allocated to the PTED or the MED group by computer-generated randomization codes. The primary outcome was the Oswestry Disability Index (ODI) score 1 year after surgery. Secondary outcomes included scores of the Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain and physical function scales, EuroQol Group's EQ-5D , and the visual analog scales for back pain and leg pain. Data including duration of operation, in-bed time, length of hospital stay, surgical cost and total hospital cost, complications, and reoperations were recorded. RESULTS A total of 153 participants were randomly assigned to 2 treatment groups (PTED vs MED), and 89.5% (137 patients) completed 1 year of follow-up. Primary and secondary outcomes did not differ significantly between the treatment groups at each prespecified follow-up point (p > 0.05). For PTED, there was less postoperative improvement in ODI score in the median herniation subgroup at 1 week (p = 0.027), 3 months (p = 0.013), 6 months (p = 0.027), and 1 year (p = 0.028) compared with the paramedian subgroup. For MED, there was significantly less improvement in ODI score at 3 months (p = 0.008), 6 months (p = 0.028), and 1 year (p = 0.028) in the far-lateral herniation subgroup compared with the paramedian subgroup. The total complication rate over the course of 1 year was 13.75% in the PTED group and 16.44% in the MED group (p = 0.642). Five patients (6.25%) in the PTED group and 3 patients (4.11%) in the MED group suffered from residue/recurrence of herniation, for which reoperation was required. CONCLUSIONS Over the 1-year follow-up period, PTED did not show superior clinical outcomes and did not seem to be a safer procedure for patients with lumbar disc herniation compared with MED. PTED had inferior results for median disc herniation, whereas MED did not seem to be the best treatment option for far-lateral disc herniation. Clinical trial registration no.: NCT01997086 (clinicaltrials.gov).

Risk factor of contralateral radiculopathy following microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion.

PURPOSE: Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. METHODS: A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). RESULTS: Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed statistical association with this complication (both P > 0.05). Based on ROC curve, the optimal threshold of preoperative CFA was 0.76 cm2. At final follow-up, significant improvement in VAS (back and leg), JOA and ODI was observed in both groups compared with preoperative baseline (all P < 0.05), while no difference was found between the two groups (all P > 0.05). CONCLUSIONS: Preoperative contralateral foramen stenosis is the risk factor of contralateral radiculopathy following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is not larger than 0.76 cm2, prophylactic measures, including both indirect and direct decompression of contralateral foramen, are recommended.