Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

Unilateral biportal endoscopic versus uniportal full-endoscopic for lumbar degenerative disease: A meta-analysis.

BACKGROUND: Despite the increasing use of unilateral biportal endoscopic (UBE) and uniportal full-endoscopic (UPFE) techniques in lumbar degenerative disease (LDD), few comprehensive and systematic studies have been published comparing UBE and UPFE. Therefore, we conducted a meta-analysis to compare the surgical outcomes of the two procedures. METHODS: We searched all studies that compared operative outcomes of UBE and UPFE for lumbar disc degeneration disease from PubMed, Google Scholar, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), Wanfang and other databases up to March 30, 2022. RESULTS: This meta-analysis, which included nine articles, showed that in operative time, (mean difference [MD]: 17.14; 95% confidence intervals [CI]: 6.52 to 27.76), intraoperative bleeding (MD: 59.01; 95% CI: 21.29 to 96.73) and hospital stay (MD: 2.12; 95% CI: 0.35 to 3.90), the UPFE group was more advantageous. UBE had an advantage in terms of postoperative dural expansion area (MD: 59.01; 95% CI: 21.29 to 96.73). These aspects included postoperative clinical score (MD: 0.48; 95% CI: -0.27 to 1.24; MD: -0.07; 95% CI: -0.30 to 0.16; MD: 0.09; 95% CI: -0.09 to 0.26; MD: 0.11; 95% CI: -0.04 to 0.26; MD: -0.81; 95% CI: -3.03 to 1.41; MD: -0.38; 95% CI: -1.02 to 0.26), excellent and good rate (odds ratio [OR] = 1.08; 95% CI: 0.34 to 3.44), complications (OR = 0.82; 95% CI: 0.31 to 2.12), postoperative hospital stay (MD: 1.63; 95% CI: -0.81 to 4.07) and mean number of fluoroscopies (MD: -7.18; 95% CI: -22.84 to 8.48), with no significant difference between the two groups. Meanwhile, the lumbar disc herniation (LDH) subgroup of UPFE had a significantly shorter operation time (MD: 31.67; 95% CI: 12.44 to 50.90) than that of UBE. CONCLUSION: Our study showed that UPFE was associated with shorter operative time, less intraoperative bleeding and shorter hospital stay, whereas UBE was associated with a greater increase in postoperative dural sac area. Postoperative visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, satisfaction rates, complications, and mean number of fluoroscopic views were not dramatically dissimilar in UBE and UPFE for LDD. In the LDH subgroup, postoperative hospital stay and operative time were significantly lower in the UPFE group than in the UBE group.

Synergetic integrations of bone marrow stem cells and transforming growth factor-ß1 loaded chitosan nanoparticles blended silk fibroin injectable hydrogel to enhance repair and regeneration potential in articular cartilage tissue.

The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-ß1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-ß1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.

Percutaneous endoscopic lumbar discectomy for LDH via a transforaminal approach versus an interlaminar approach: a meta-analysis.

PURPOSE: The aim of this study was to systematically compare the safety and effectiveness of percutaneous endoscopic transforaminal discectomy (PETD) versus percutaneous endoscopic interlaminar discectomy (PEID) for the treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS: All studies that were performed to compare PETD with PEID to treat LDH and published until 31 August 2017 were acquired through a comprehensive search in various databases. A meta-analysis was performed using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: A total of 13 trials with 974 cases consisting of 3 randomized controlled trials, 3 prospective studies and 7 retrospective studies were included. The results suggest that patients treated with PEID experienced more significant advantages with shorter operation time, less intraoperative blood loss and less intraoperative fluoroscopy times but more complications than those treated with PETD; however, the two operative approaches did not significantly differ in terms of LDH recurrence, hospital stay, Oswestry disability index (ODI) scores, visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores and MacNab criteria at the final follow-up. CONCLUSION: Based on the results of this study, although PEID may be superior to PETD in certain ways, some of its advantages have yet to be verified and the two interventions were not significantly different in terms of relief of symptoms and functional recovery. Therefore, PEID would be recommended for treating LDH especially at L5/S1 under certain conditions but a prudent attitude is necessary to choose between the two operative approaches before a large sample and high quality randomized controlled trials have been performed.

Periodic Mechanical Stress Induces Extracellular Matrix Expression and Migration of Rat Nucleus Pulposus Cells Through Src-GIT1-ERK1/2 Signaling Pathway.

BACKGROUND/AIMS: Periodic mechanical stress has been shown to promote extracellular matrix (ECM) synthesis and cell migration of nucleus pulposus (NP) cells, however, the mechanisms need to be fully elucidated. The present study aimed to investigate the signal transduction pathway in the regulation of NP cells under periodic mechanical stress. METHODS: Primary rat NP cells were isolated and seeded on glass slides, and then treated in our self-developed periodic stress field culture system. To further explore the mechanisms, data were analyzed by scratch-healing assay, quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, western blotting, and co-immunoprecipitation assay. RESULTS: Under periodic mechanical stress, the mRNA expression of ECM collagen 2A1 (Col2A1) and aggrecan, and migration of NP cells were significantly increased (P < 0.05 for each), associating with increases in the phosphorylation of Src, GIT1, and ERK1/2 (P < 0.05 for each). Pretreatment with the Src inhibitor PP2 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each), while the phosphorylation of GIT1 and ERK1/2 were inhibited. ECM synthesis, cell migration, and phosphorylation of ERK1/2 were inhibited after pretreatment with the small interfering RNA for GIT1 in NP cells under periodic mechanical stress (P < 0.05 for each), whereas the phosphorylation of Src was not affected. Pretreatment with the ERK1/2 inhibitor PD98059 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each). Co-immunoprecipitation assay showed that there was a direct interaction between Src and GIT1 and between GIT1 and ERK1/2. CONCLUSION: In conclusion, periodic mechanical stress induced ECM expression and migration of NP cells via Src-GIT1-ERK1/2 signaling pathway, playing an important role in regulation of NP cells.

Meta-analysis of percutaneous transforaminal endoscopic discectomy vs. fenestration discectomy in the treatment of lumbar disc herniation.

OBJECTIVE: The aim of this study was to systematically review the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) and fenestration discectomy (FD) in the treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wanfang Data for all relevant studies. All statistical analyses wer performed using Review Manager version 5.3. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (CI). RESULTS: A total of 17 articles with 1390 study subjects were included, with 733 patients in the PTED group and 657 patients in the FD group. The results of the meta-analysis showed that postoperative the visual analog scale (VAS) score (mean difference [MD] -0.13; 95% confidence interval [CI] -0.22 to -0.03; P = 0.009) and postoperative complications (MD 0.52; 95% CI 0.26 to 1.04; P = 0.06) showed no significant differences between the PTED group and the FD group, while the PTED group had significantly better results in operation time (MD 0.47; 95% CI -11.34 to 12.28; P = 0.94), length of incision (MD -3.74; 95% CI -4.28 to -3.19; P < 0.00001), amount of bleeding (MD -63.66, 95% CI -77.65 to -49.67; P < 0.00001), time of postoperative bed rest (MD -90.19; 95% CI -106.82 to -73.56; P < 0.00001), hospitalization time (MD -5.90; 95% CI -7.21 to -4.59; P < 0.00001), and postoperative Oswestry disability index (ODI) score (MD -0.59; 95% CI -1.11 to -0.08; P = 0.02) compared with the FD group. CONCLUSION: The Percutaneous transforaminal endoscopic discectomy is associated with better postoperative ODI score, better results in length of incision, lower blood loss, shorter operation time, postoperative bed time and hospitalization time. The complications did not differ significantly between PTED and FD in the treatment of lumbar disc herniation. These findings provide evidence to support PTED is efficacious for LDH; however, scar repair of a ruptured anulus fibrosus needs a long time and the patients undergoing PTED should be advised to stay in bed for a long time even if the symptoms are markedly relieved. These results are not limited to randomized controlled trials and lack data about the long-term outcome.

Is Full-Endoscopic Transforaminal Lumbar Interbody Fusion Superior to Open Transforaminal Lumbar Interbody Fusion for Single-Level Degenerative Lumbar Spondylolisthesis? A Retrospective Study.

BACKGROUND: In this study, we evaluate the clinical efficacy and safety of full-endoscopic transforaminal lumbar interbody fusion (TLIF) for treatment of single-level lumbar degenerative spondylolisthesis. METHODS: Fifty-three patients were divided into two groups according to the surgical techniques: Full endoscopic (Endo)-TLIF (n = 25) and TLIF (n = 28). Clinical efficacy was evaluated pre- and postoperatively. The operation time, operative blood loss, postoperative amount of serum creatine phosphokinase (CPK), postoperative drainage volume, postoperative hospital stay time, total cost, and operative complications were also recorded. RESULTS: Compared with the TLIF group, the Endo-TLIF group had similar intraoperative blood loss, less postoperative increased CPK, less postoperative drainage volume, and shorter postoperative hospital stay, but longer operative time and higher total cost. The postoperative visual analog scale (VAS) scores of back and leg pain and Oswestry Disability Index (ODI) scores significantly improved compared with the preoperative scores in both two groups; more significant improvement of postoperative VAS scores of back pain and ODI scores were shown in the Endo-TLIF group at the 1-month follow-up (p < 0.05). No difference was found in the intervertebral fusion rate between the two groups. CONCLUSION: The Endo-TLIF has similar clinical effect compared with the TLIF for the treatment of lumbar degenerative spondylolisthesis. It also has many surgical advantages such as less muscle trauma, less postoperative back pain, and fast functional recovery of the patient. However, steep learning curve, longer operative time, and higher total cost may be the disadvantages that limit this technique. Also, the Endo-TLIF treatment of patients with bilateral lateral recess stenosis is considered a relative contraindication.

Early Clinical and Radiologic Evaluation of Unilateral Biportal Endoscopic Unilateral Laminotomy and Bilateral Decompression in Degenerative Lumbar Spinal Stenosis: A Retrospective Study.

BACKGROUND: The aim of this study is to evaluate the changes in radiologic parameters and clinical outcomes following unilateral biportal endoscopic unilateral laminotomy and bilateral decompression (UBE ULBD) for treatment of central lumbar spinal stenosis. METHODS: Forty-one central lumbar spinal stenosis patients who underwent UBE ULBD were enrolled from April 2021 to February 2023. Visual analog scale (VAS) for back pain and leg pain, Oswestry Disability Index (ODI) score, and the modified MacNab criteria were assessed preoperatively and postoperatively. The preoperative and postoperative cross-sectional area of the spinal canal (CSAC), anteroposterior diameter, horizontal width, and ipsilateral and contralateral lateral recess height were calculated from axial computed tomography (CT) scans. Percentage of facet joint preservation measured on axial CT scans was obtained preoperation and postoperation. RESULTS: The VAS for back and leg pain improved from 7.24 ± 0.80 and 7.59 ± 0.59 preoperatively to 2.41 ± 0.55 and 2.37 ± 0.62 (p < 0.05) postoperatively and 1.37 ± 0.54 and 1.51 ± 0.55 at the last follow-up (p < 0.05). For ODI, improvement from 60.37 ± 4.44 preoperatively to 18.90 ± 4.66 (p < 0.05) at the last follow-up was observed. CT scans demonstrated that the postoperative CSAC increased significantly from 287.84 ± 87.81 to 232.97 ± 88.42 mm (p < 0.05). The mean postoperative anteroposterior diameter and horizontal width increased significantly from 18.01 ± 3.13 and 19.57 ± 3.80 to 22.19 ± 4.56 and 21.04 ± 3.72 mm, respectively (p < 0.05). The ipsilateral lateral recess height and contralateral lateral recess height were 3.39 ± 1.12 and 3.20 ± 1.14 mm preoperatively and 4.03 ± 1.37 and 3.83 ± 1.32 mm (p < 0.05) postoperatively, with significant differences. The ipsilateral and contralateral facet joint preservations were 88.17 and 93.18%, respectively. CONCLUSION: The UBE ULBD surgery is a safe and effective treatment for central lumbar spinal stenosis, associated with significant improvement in clinical outcomes and radiologic parameters. Studies with larger samples and longer follow-up periods are needed for further research.

Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Local Anesthesia Versus General Anesthesia in Percutaneous Interlaminar Endoscopic Discectomy: A Meta-analysis.

OBJECTIVE: The objective of this study was to systematically evaluate the safety and efficacy of local anesthesia (LA) and general anesthesia (GA) in percutaneous interlaminar endoscopic discectomy (PIED). MATERIALS AND METHODS: We searched MEDLINE, EMBASE, EuropePMC, PubMed, Web of Science, Cochrane databases, and CNKI databases for all relevant studies. All statistical analysis was performed using Review Manager version 5.3. RESULTS: A total of 6 articles with 549 study participants were included, with 282 patients in LA group and 267 patients in GA group. The results of the meta-analysis showed that the LA group had significantly better results in hospital stay time (mean difference [MD], -1.68; 95% CI, -3.35 to -0.01) and hospital costs (MD, -0.57, 95% CI, -1.02 to -0.12) compared with the GA group; whereas Oswestry Disability Index (MD, 0.48; 95% CI, -0.07 to 1.04), Visual Analog Scale Scores (MD, -0.05; 95% CI, -0.24 to 0.13), postoperative transient dysesthesia and weakness (odds ratio [OR], 0.83, 95% CI, 0.40 to 1.69), dura and nerve root injury (OR, 0.21, 95% CI, 0.03 to 1.25), operation time (MD, -3.51; 95% CI, -11.5 to 4.48), and willingness rate to receive the same procedure(OR, 0.12, 95% CI, 0.01 to 1.00) showed no significant differences between the 2 groups. DISCUSSION: LA can effectively relieve pain during PIED surgery and ensure the safety of operation without increasing the occurrence of postoperative complications. PIED under LA not only has similar patient satisfaction but also shows obvious advantages in shortening hospital stay and reducing hospital costs compared with GA surgery.

Comparison of Complications between Anterior Cervical Diskectomy and Fusion versus Anterior Cervical Corpectomy and Fusion in Two- and Three-Level Cervical Spondylotic Myelopathy: A Meta-analysis.

BACKGROUND: In this study, we systematically analyze the differences in complications between anterior cervical diskectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) in two- and three-level cervical spondylotic myelopathy (CSM). METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wan Fang Data for all relevant studies. All statistical analyses were performed using Review Manager version 5.3. RESULTS: A total of 11 articles with 849 study subjects were included, with 474 patients in the ACDF group and 375 patients in the ACCF group. The results of the meta-analysis showed that in C5 palsy (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.16-1.06), pseudarthrosis (OR: 1.07; 95% CI: 0.23-5.07), dysphagia (OR: 1.06; 95% CI: 0.60-1.86), infection (OR: 0.41; 95% CI: 0.16-1.09), cerebrospinal fluid leakage (OR: 1.21; 95% CI: 0.39-3.73), graft dislodgment (OR: 0.28; 95% CI: 0.06-1.37), and hematoma (OR: 0.32; 95% CI: 0.06-1.83), there are no significant differences between the ACDF and ACCF groups, whereas total complication (OR: 0.50; 95% CI: 0.31-0.80) showed that the ACDF group had a significantly lower morbidity than the ACCF group. Furthermore, the three-level subgroup of ACDF had significantly better results in C5 palsy (OR: 0.31; 95% CI: 0.11-0.88), infection (OR: 0.22; 95% CI: 0.05-0.94), graft dislodgment (OR: 0.07; 95% CI: 0.01-0.40), and total complication (OR: 0.37; 95% CI: 0.23-0.60) compared with the ACCF subgroup. CONCLUSION: In general, postoperative pseudarthrosis, dysphagia, cerebrospinal fluid leakage, hematoma, C5 palsy, infection, and graft dislodgment did not differ significantly between the two groups. Total complication was significantly less in the ACDF group compared to the ACCF group. In the three-level subgroup, the morbidity of C5 palsy, infection, and graft dislodgment was significantly lower in ACDF than in ACCF.

Percutaneous Curved Vertebroplasty and Bilateral-Pedicle-Approach Percutaneous Vertebroplasty in the Treatment of Osteoporotic Vertebral Compression Fracture: A Meta-Analysis.

Introduction: The aim of this study was to evaluate the use of percutaneous curved vertebroplasty procedure (PCVP) and bilateral-pedicle-approach percutaneous vertebroplasty (bPVP) for the treatment of osteoporotic vertebral compression fractures (OVCFs) through a systematic review and meta-analysis of the scientific literature. Methods: A systematic review of the scientific literature in PubMed, China National Knowledge Infrastructure (CNKI), Wanfang and other databases was conducted in conjunction with different keywords. Nine studies were included; all but 3 were randomised controlled studies and all were prospective or retrospective cohort studies. Results: We observed statistically significant differences between the PCVP group and the bPCVP group in terms of postoperative visual analogue scale (VAS) scores (mean difference [MD]: -.08; 95% confidence intervals [CI]: -.15 to .00), bone cement leakage rates (OR = .33; 95%CI: .20 to .54), bone cement injection (MD: -1.52; 95%CI: -1.58 to 1.45), operative times (MD: -16.69; 95%CI: -17.40 to -15.99) and intraoperative fluoroscopies (MD: -8.16; 95%CI: -9.56 to -6.67), with the PCVP group being more dominant. There were no statistical differences in postoperative Oswestry Disability Index (ODI) scores (MD: -.72; 95%CI: -2.11 to .67) and overall bone cement distribution rates (MD: 2.14; 95%CI: .99 to 4.65) between the 2 groups. Conclusions: Meta-analysis showed more favourable outcomes in the PCVP group compared to the bPVP group. PCVP might be effective and safe in the treatment of OVCFs because it relieves postoperative patient pain, reduces operative time and cement injection, and decreases the risk of cement leakage and radiation exposure to the surgeon and patient.

CK1ε drives osteogenic differentiation of bone marrow mesenchymal stem cells via activating Wnt/ß-catenin pathway.

The treatment of bone defects is a difficult problem in orthopedics. At present, the treatment mainly relies on autologous or allogeneic bone transplantation, which may lead to some complications such as foreign body rejection, local infection, pain, or numbness at the bone donor site. Local injection of conservative therapy to treat bone defects is one of the research hotspots at present. Bone marrow mesenchymal stem cells (BMSCs) can self-renew, significantly proliferate, and differentiate into various types of cells. Although it has been reported that CK1ε could mediate the Wnt/ß-catenin pathway, leading to the development of the diseases, whether CK1ε plays a role in bone regeneration through the Wnt/ß-catenin pathway has rarely been reported. The purpose of this study was to investigate whether CK1ε was involved in the osteogenic differentiation (OD) of BMSCs through the Wnt/ß-catenin pathway and explore the mechanism. We used quantitative reverse transcription-polymerase chain reaction (qRT-qPCR), Western blots, immunofluorescence, alkaline phosphatase, and alizarin red staining to detect the effect of CK1ε on the OD of BMSCs and the Wnt/ß-catenin signaling pathway. CK1ε was highly expressed in BMSCs with OD, and our study further demonstrated that CK1ε might promote the OD of BMSCs by activating DLV2 phosphorylation, initiating Wnt signaling downstream, and activating ß-catenin nuclear transfer. In addition, by locally injecting a CK1ε-carrying adeno-associated virus (AAV5- CK1ε) into a femoral condyle defect rat model, the overexpression of CK1ε significantly promoted bone repair. Our data show that CK1ε was involved in the regulation of OD by mediating Wnt/ß-catenin. This may provide a new strategy for the treatment of bone defects.

Discovery and validation of bladder cancer related excreted nucleosides biomarkers by dilution approach in cell culture supernatant and urine using UHPLC-MS/MS.

The exploration of nucleoside changes in human biofluids has profound potential for cancer diagnosis. Herein, we developed a rapid methodology to quantify 17 nucleosides by UHPLC-MS/MS. Five pairs of isomers were successfully separated within 8 min. The ME was mostly eliminated by sample dilution folds of 1000 for urine and 40 for CCS. The optimized method was firstly applied to screen potential nucleoside biomarkers in CCS by comprising bladder cancer cell lines (5637 and T24) and normal human bladder cell line SV-HUC-1 together with student's t-test and OPLS-DA. Nucleosides with significant differences in the supernatant of urine samples were also uncovered comparing BCa with the non-tumor group, as well as a comparison of BCa recurrence group with the non-recurrence group. By intersecting the differential nucleosides in CCS and urine supernatant, and then further confirmed using validation sets, the combination of m3C and m1A with AUC of 0.775 was considered as a potential biomarker for bladder cancer diagnosis. A panel of m3C, m1A, m1G, and m22G was defined as potential biomarkers for bladder cancer prognosis with an AUC of 0.819. Above all, this method provided a new perspective for diagnosis and recurrence monitoring of bladder cancer. SIGNIFICANCE: The exploration of nucleoside changes in body fluids has profound potential for the diagnosis and elucidation of the pathogenesis of cancer. In this study, we developed a rapid methodology for the simultaneous quantitative determination of 17 nucleosides in the supernatant of cells and urine samples using UHPLC-MS/MS to discover and validate bladder cancer related excreted nucleoside biomarkers. The results of this paper provide a new strategy for diagnosis and postoperative recurrence monitoring of bladder cancer and provide theoretical support for the exploration of its pathogenesis.

Uniportal Full-Endoscopic versus Minimally Invasive Decompression for Lumbar Spinal Stenosis: A Meta-analysis.

BACKGROUND: In this study, we systematically analyze the effectiveness of the uniportal full-endoscopic (UPFE) and minimally invasive (MIS) decompression for treatment of lumbar spinal stenosis patients. METHODS: We performed a systematic search in Medline, Embase, Europe PMC, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, China national knowledge infrastructure, and Wanfang Data databases for all relevant studies. All statistical analyses were performed using Review Manager version 5.3. RESULTS: A total of 9 articles with 522 patients in the UPFE group and 367 patients in the MIS group were included. The results of the meta-analysis showed that the UPFE group had significantly better results in hospital stay time (mean difference [MD]: -2.05; 95% confidence interval [CI]: -2.87 to -1.23), intraoperative blood loss (MD: -36.56; 95% CI: -54.57 to -18.56), and wound-related complications (MD: -36.56; 95%CI: -54.57 to -18.56) compared with the MIS group, whereas the postoperative clinical scores (MD: -0.66; 95%CI: -1.79 to 0.47; MD: -0.75; 95%CI: -1.86 to 0.36; and MD: -4.58; 95%CI: -16.80 to 7.63), satisfaction rate (odds ratio [OR] = 1.24; 95%CI: 0.70-2.20), operation time (MD: 30.31; 95%CI: -12.55 to 73.18), complication rates for dural injury (OR = 0.60; 95%CI: 0.29-1.26), epidural hematoma (OR = 0.60; 95%CI: 0.29-1.26), and postoperative transient dysesthesia and weakness (OR = 0.73; 95%CI: 0.36-1.51) showed no significant differences between the two groups. CONCLUSIONS: The UPFE decompression is associated with shorter hospital stay time and lower intraoperative blood loss and wound-related complications compared with MIS decompression for treatment of lumbar spinal stenosis patients. The postoperative clinical scores, satisfaction rate, operation time, complication rates for dural injury, epidural hematoma, and postoperative transient dysesthesia and weakness did not differ significantly between two groups.

[Experimental study on the construction of telmisartan/collagen/polycaprolactone nerve conduit and its repair effect on rat sciatic nerve defect].

Objective: To construction the telmisartan/collagen/polycaprolactone (PCL) nerve conduit and assess its effect on repairing sciatic nerve defect in rats. Methods: The 60% collagen/hexafluoroisopropanol (HFIP) solution and 40% PCL/HFIP solution were prepared and mixed (collagen/PCL solution). Then the 0, 5, 10, and 20 mg of telmisartan were mixed with the 10 mL collagen/PCL solution, respectively. Telmisartan/collagen/PCL nerve conduits were fabricated via high voltage electrospinning technology. The structure of nerve conduit before and after crosslinking was observed by using scanning electron microscope (SEM). The drug release efficiency was detected by in vitro sustained release method. RAW264.7 cells were cultured with lipopolysaccharide to induce inflammation, and then co-cultured with nerve conduits loaded with different concentrations of telmisartan for 24 hours. The mRNA expressions of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg-1) were detected by using real-time fluorescence quantitative PCR. Forty adult Wistar rats were randomly divided into 4 groups ( n=10). After preparing 15-mm-long sciatic nerve defect, the defect was repaired by cross-linked nerve conduits loaded with 0, 5, 10, and 20 mg telmisartan in groups A, B, C, and D, respectively. After operation, the general condition of rats was observed after operation; the sciatic function index (SFI) was tested; the bridging between the nerve conduit and sciatic nerve, and the integrity of nerve conduit were observed; the tissue growth in nerve conduit and material degradation were observed by HE staining; the expressions of CD86 (M1 macrophage marker), CD206 (M2 macrophage marker), myelin basic protein (MBP), and myelin protein 0 (P0) in new tissues were also observed by immunohistochemical staining; the expressions of neurofilament 200 (NF-200) and S-100ß in new tissues were assessed by immunofluorescence staining. Results: The general observation showed that the inner diameter of the nerve conduit was 1.8 mm and the outer diameter was 2.0 mm. After cross-linking by genipin, the nanofiber became thicker and denser. The drug release test showed that the telmisartan loaded nerve conduit could be released gradually. With the increase of telmisartan content in nerve conduit, the iNOS mRNA expression decreased and the Arg-1 mRNA expression increased; and the differences between 20 mg group and other groups were significant ( P<0.05). In vivo experiment showed that all animals in each group survived until the completion of the experiment. The SFI was significantly higher in groups C and D than in groups A and B at different time points ( P<0.05) and in group D than in group C at 6 months after operation ( P<0.05). HE staining showed that there were significantly more new tissues in the middle of the nerve conduit in group D after operation than in other groups. Immunohistochemical staining showed that CD86 and CD206 stainings were positive in each group at 1 month after operation, among which group D had the lowest positive rate of CD86 and the highest positive rate of CD206, and there were significant differences in the positive rate of CD206 between group D and groups A, B, and C ( P<0.05); the MBP and P0 stainings were positive in groups C and D at 6 months, and the positive rate in group D was significantly higher than that in group C ( P<0.05). Immunofluorescence staining showed that the NF-200 and S-100ß expressions in group D were significantly higher than those in other groups. Conclusion: Telmisartan/collagen/PLC nerve conduit can promote the sciatic nerve defect repair in rats through promoting the polarization of M1 macrophages to M2 macrophages, and the nerve conduit loaded with20 mg telmisartan has the most significant effect.

Anatomic reconstruction of the anterior cruciate ligament of the knee with or without reconstruction of the anterolateral ligament: A meta-analysis.

PURPOSE: To systematically analyze the effectiveness between combined anterior cruciate ligament and anterolateral ligament reconstruction (ACL+ALLR) and isolated anterior cruciate ligament reconstruction (ACLR) for treatment of patients with injured ACL. METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wanfang Data for all relevant studies. All statistical analysis was performed using Review Manager version 5.3. RESULTS: A total of six articles with 460 study subjects were included, with 193 patients in ACL+ALL reconstruction group and 267 patients in ACL reconstruction group. The results of the meta-analysis showed that the ACL+ALL reconstruction group had significantly lower KT measured value (P < 0.00001), Lachman test positive-rate (P = 0.02), Pivot-shift test positive-rate (P < 0.00001) and graft rupture rate (P = 0.02) compared with the ACL reconstruction group. Higher IKDC score (P < 0.00001) and Lysholm score (P < 0.00001) were measured in ACL+ALL reconstruction group, while infection rate (P = 0.86) and other complications rate (P = 0.29) showed no significant differences between the two groups. CONCLUSIONS: Anatomic reconstruction of the ACL of the knee with reconstruction of the ALL indicates better postoperative knee function and clinical outcomes compared with isolated ACL reconstruction. The infection rate and other complications rate showed no significant difference between two groups.

Enhanced In Vitro and In Vivo Efficacy of Alginate/Silk Protein/Hyaluronic Acid with Polypeptide Microsphere Delivery for Tissue Regeneration of Articular Cartilage.

Alginate/Silk fibroin/hyaluronic acid (ALG/SF/HA) nanocomposites were synthesised using blending, inter-linking, and lyophilization methods. We investigated the physicochemical properties of the resulting nanocomposites, including their water retention, weight loss, porosity and cytocompatibility. The optimum ratios of the ALG/SF/HA scaffolding were 3:6.5:0.5. Nanocomposites with optimum ratios were then prepared by integrating pilose antler polypeptides (PAPS) to poly(lactic-co-glycolic acid) (PLGA) microspheres, and the performance was investigated. PAPS-ALG/SF/HA nanocomposites exhibited desirable adhesions and proliferations. Rabbit cartilage deficiencies was developed by the animal model. The cartilage repair effects deficiencies were detected and analyzed between PAPS-SF/ALG/ALG/SF/HA, and control activity classes. The deficiencies were virtually fully remedied after 13 weeks in the presence of PAPS-ALG/SF/HA class, suggesting that the PAPS-ALG/SF/HA nanocomposites had a positive effects on joint cartilage repair.

A Novel CpG Methylation Risk Indicator for Predicting Prognosis in Bladder Cancer.

PURPOSE: Bladder cancer (BLCA) is one of the most common cancers worldwide. In a large proportion of BLCA patients, disease recurs and/or progress after resection, which remains a major clinical issue in BLCA management. Therefore, it is vital to identify prognostic biomarkers for treatment stratification. We investigated the efficiency of CpG methylation for the potential to be a prognostic biomarker for patients with BLCA. PATIENTS AND METHODS: Overall, 357 BLCA patients from The Cancer Genome Atlas (TCGA) were randomly separated into the training and internal validation cohorts. Least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) were used to select candidate CpGs and build the methylation risk score model, which was validated for its prognostic value in the validation cohort by Kaplan-Meier analysis. Hazard curves were generated to reveal the risk nodes throughout the follow-up. Gene Set Enrichment Analysis (GSEA) was used to reveal the potential biological pathways associated with the methylation model. Quantitative real-time polymerase chain reaction (PCR) and western blotting were performed to verify the expression level of the methylated genes. RESULTS: After incorporating the CpGs obtained by the two algorithms, CpG methylation of eight genes corresponding to TNFAIP8L3, KRTDAP, APC, ZC3H3, COL9A2, SLCO4A1, POU3F3, and ADARB2 were prominent candidate predictors in establishing a methylation risk score for BLCA (MRSB), which was used to divide the patients into high- and low-risk progression groups (p < 0.001). The effectiveness of the MRSB was validated in the internal cohort (p < 0.001). In the MRSB high-risk group, the hazard curve exhibited an initial wide, high peak within 10 months after treatment, whereas some gentle peaks around 2 years were noted. Furthermore, a nomogram comprising MRSB, age, sex, and tumor clinical stage was developed to predict the individual progression risk, and it performed well. Survival analysis implicated the effectiveness of MRSB, which remains significant in all the subgroup analysis based on the clinical features. A functional analysis of MRSB and the corresponding genes revealed potential pathways affecting tumor progression. Validation of quantitative real-time PCR and western blotting revealed that TNFAIP8L3 was upregulated in the BLCA tissues. CONCLUSION: We developed the MRSB, an eight-gene-based methylation signature, which has great potential to be used to predict the post-surgery progression risk of BLCA.

Transforaminal approach versus interlaminar approach: A meta-analysis of operative complication of percutaneous endoscopic lumbar discectomy.

BACKGROUND: To systematically analyze the differences of complications between percutaneous transforaminal endoscopic discectomy (PTED) and percutaneous interlaminar endoscopic discectomy (PIED) in the treatment of lumbar disc herniation. METHODS: We performed a systematic search in MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases, Chinese Biomedical Literature Database, CNKI, and Wanfang Data for all relevant studies. All statistical analysis was performed using Review Manager Version 5.3. RESULTS: A total of 15 articles with 1156 study subjects were included, with 550 patients in PTED group and 606 patients in PIED group. The results of the meta-analysis showed that postoperative dysesthesia (odds ratio [OR] = 0.61, 95% confidence interval [CI], 0.33-1.13), nerve root injury (OR = 1.22, 95% CI, 0.30-5.02), surgical site wound complications (OR = 1.26, 95% CI, 0.29-5.40), recurrence (OR = 1.09, 95% CI, 0.54-2.21), conversion to open surgery (OR = 1.26, 95% CI, 0.33-4.81), incomplete decompression (OR = 1.62, 95% CI, 0.43-6.09), and total complication (OR = 0.72, 95% CI, 0.49-1.06) showed no significant differences between the PTED group and the PIED group, while the PTED group had significantly better results in dural tear compared with the PIED group (OR = 0.31, 95% CI, 0.13-0.79). CONCLUSIONS: Dural tear was significantly less occured in PTED compared with PIED. The postoperative dysesthesia, nerve root injury, surgical site wound complications, recurrence, conversion to open surgery, incomplete decompression, and total complication did not differ significantly between PTED and PIED in the treatment of lumbar disc herniation.