Association of noncoding RNAs with Kawasaki disease: A meta-analysis based on the current evidences.

BACKGROUND: In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are associated with the occurrence and development of KD. Thus, we performed a systematic review and meta-analysis to investigate the diagnostic value of ncRNAs in KD patients. METHODS: We searched the PubMed, Web of Science, Embase and Cochrane Library, China National Knowledge Infrastructure, VIP, China Biology Medicine disc databases, and Wanfang databases until August 25, 2023 and screened all eligible studies focusing on the diagnostic performance of ncRNAs in KD patients. RESULTS: In total, 535 articles were found, and 28 articles were included in this systematic review and meta-analysis. The calculated area under the curve value was 0.880 (95% confidence intervals, 0.840-0.900). The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.790, 0.830, 4.610, and 0.260, respectively. The pooled diagnostic odds ratio was 17.890 (95% confidence intervals, 13.110-24.420), indicating a relatively good diagnostic performance of the ncRNAs for detecting KD. In addition, the diagnostic value of micro RNAs in KD was better than that of long noncoding RNAs and circular noncoding RNAs. A subgroup analysis by specimen indicated a better diagnostic value of ncRNAs in plasma and platelet than serum. The diagnostic accuracy of ncRNAs was better in febrile controls than in healthy control groups, indicating a relatively good accuracy in distinguishing KD patients from febrile diseases. CONCLUSIONS: This systematic review and meta-analysis demonstrated that ncRNAs could be used as novel biomarkers for detecting KD. More studies should be conducted in the future to verify the diagnostic values of ncRNAs in KD.

Culture and identification of neonatal rat brain-derived neural stem cells.

BACKGROUND: Timing of passaging, passage number, passaging approaches and methods for cell identification are critical factors influencing the quality of neural stem cells (NSCs) culture. How to effectively culture and identify NSCs is a continuous interest in NSCs study while these factors are comprehensively considered. AIM: To establish a simplified and efficient method for culture and identification of neonatal rat brain-derived NSCs. METHODS: First, curved tip operating scissors were used to dissect brain tissues from new born rats (2 to 3 d) and the brain tissues were cut into approximately 1 mm3 sections. Filter the single cell suspension through a nylon mesh (200-mesh) and culture the sections in suspensions. Passaging was conducted with TrypLTM Express combined with mechanical tapping and pipetting techniques. Second, identify the 5th generation of passaged NSCs as well as the revived NSCs from cryopreservation. BrdU incorporation method was used to detect self-renew and proliferation capabilities of cells. Different NSCs specific antibodies (anti-nestin, NF200, NSE and GFAP antibodies) were used to identify NSCs specific surface markers and muti-differentiation capabilities by immunofluorescence staining. RESULTS: Brain derived cells from newborn rats (2 to 3 d) proliferate and aggregate into spherical-shaped clusters with sustained continuous and stable passaging. When BrdU was incorporated into the 5th generation of passaged cells, positive BrdU cells and nestin cells were observed by immunofluorescence staining. After induction of dissociation using 5% fetal bovine serum, positive NF200, NSE and GFAP cells were observed by immunofluorescence staining. CONCLUSION: This is a simplified and efficient method for neonatal rat brain-derived neural stem cell culture and identification.

Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain-lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin-triggered lipoxin A4 is a potent anti-inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood-brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti-neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment.

Diagnostic significance of noncoding RNAs in kawasaki disease: A systematic review and meta-analysis.

Objective: Kawasaki disease (KD) is a systemic vasculitis disease, and early effective intervention would reduce the occurrence of coronary artery lesions (CALs). Recently, many scholars have been committed to studying the relationship between noncoding RNAs and KD. This systematic review aimed to analyze the diagnostic value of noncoding RNAs(ncRNAs) in distinguishing different KD status. Methods: We searched for the literature about diagnostic values of ncRNAs in KD in CNKI, VIP, Wanfang, China Biomedical Literature Database as well as PubMed, Web of Science, Embase, and Cochrane Library up to April 15, 2022. All included studies were further analyzed using STATA 12.0, Meta-disc 1.4 and RevMan 5.4 software. Results: A total of six studies investigating the diagnostic performance of ncRNAs in differentiating KD-CAL (n = 101) from KD-NCAL patients (n = 123) were included in this this meta-analysis. The calculated area under the curve(AUC) was 0.83 (0.80-0.86). Four studies on the diagnostic performance of ncRNAs in differentiating acute KD patients (n = 139) from convalescent KD patients (n = 109) were included. The calculated AUC was 0.87 (0.84-0.90). Four studies focused on the diagnostic performance of ncRNAs combined with other laboratory indexes in KD by assessing 137 KD patients and 152 febrile controls. The calculated AUC was 0.90 (0.87-0.92). Four studies assessed the diagnostic performance of ncRNAs in differentiating intravenous immunoglobulin (IVIG)-resistant KD patients from IVIG-responsive KD patients. The calculated AUC was 0.9135 ± 0.0307. These results indicated that ncRNAs have a good diagnostic efficacy in KD. Conclusions: This meta-analysis showed that ncRNAs have potential as a biomarker for distinguishing different KD status. However, since limited studies were included in this meta-analysis, larger and well-designed diagnostic studies should be conducted to validate these results. Systematic Review Registration: INPLASY.COM, identifier: doi: 10.37766/inplasy2022.10.0035.

[Analysis of SIK3 gene variation in a boy with autism spectrum disorder complicated with epilepsy].

OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION: The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.

Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis.

AIMS: Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. METHODS: In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. RESULTS: We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. CONCLUSION: Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328-339.

Tranexamic acid reduces blood cost in long-segment spinal fusion surgery: A randomized controlled study protocol.

OBJECTIVE: Long-segment spinal fusion surgery was associated with substantial perioperative blood loss which may increase hospitalization expenses and mortality rates. Substantial studies have reported that tranexamic acid (TXA) could reduce blood products and cost after joint arthroplasty surgery. However, there still exists controversy regarding the efficacy of TXA in long-segment spinal fusion surgery. We performed this protocol to design a randomized controlled study to evaluate the efficacy of TXA in decreasing transfusion rate of allogeneic blood products and transfusion cost in degenerative lumbar scoliosis patients. METHODS: This study was carried out as a double-blinded, randomized clinical trial on patients with degenerative lumbar scoliosis who prepared for long-segment spinal fusion surgery from December 2018 to December 2019. It was authorized via the Institutional Review Committee in Southwest Medical University (ky2019225). Eighty patients were divided randomly into 2 groups (Experimental group = 40, control group = 40). The patients in the experimental group received 1000 mg of TXA mixed in 100 mL normal saline as a single dose intravenously over 20 minutes before the skin incision was made. Control group received equivalent normal saline without TXA. Primary outcomes included total blood loss, estimated intraoperative blood loss, hematocrit and hemoglobin decline, postoperative drain amount, intra-/postoperative allogeneic transfusion amount and rate, and total transfusion cost. Secondary outcomes included surgical time, thrombotic complications including deep vein thrombosis and pulmonary embolism. All the needed analyses were implemented through utilizing SPSS for Windows Version 20.0. RESULTS: Table showed the relevant clinical outcomes between experimental group and control group. CONCLUSION: We hypothesized that TXA was effective and safe in reducing blood transfusion and cost in long-segment spinal fusion surgery. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5854).

Cervical arthroplasty versus anterior cervical discectomy in the treatment of symptomatic cervical spondylosis: A protocol.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are both the effective techniques in treatment of cervical spondylosis. The purpose of this present retrospective cohort research was to assess the efficacy and safety of ACDF and CDA in treating the symptomatic cervical spondylosis over the 6-year follow-up. METHODS: From our registry database, we identified retrospectively patients who received CDA or ACDF in our academic institutions from 2012 to 2015. The study was approved by the Institutional Review Board in Zigong No.4 People's Hospital (Z10058072). All the subjects who participated in this trial were informed consent in writing. The inclusion criteria were the degenerative disc diseases between C3-7 resulting in myelopathy or radiculopathy, which was unresponsive to the conservative treatment. The clinical results were determined via Short Form-36, and neck disability index, numerical scoring scales for complications, arm pain and neck pain. The radiographic assessment contained the cervical lordosis, and the motion range of the functional spinal unit and total cervical spine. The routine follow-up was performed to collect the data of radiographic and clinical assessment at 6, 12, 24, 48, and 72 months before and after the surgery. RESULTS: This study had limited inclusion and exclusion criteria and a well-controlled intervention. It was assumed that both techniques could obtain the similar postoperative effects. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5878).

A randomized study protocol of microendoscopic versus open discectomy in treatment of lumbar disc herniation.

BACKGROUND: Lumbar disk herniation (LDH) is one of the main causes of discogenic low back pain. However, the evidence comparing different approaches for discectomy has lacked definitive conclusions, with conflicting results regarding the benefit of minimally invasive versus open techniques for LDH. We are now conducting a randomized controlled trial to figure out whether or not microendoscopic discectomy yields better clinical outcomes and causes less surgical trauma than open surgery. METHODS: This prospective, randomized, single-blind, controlled, superiority clinical trial was approved by the institutional review board in the People's Hospital of Jianyang City. The conduct of this study followed the Declaration of Helsinki principles and the reporting of this study adhered to the Consolidated Standards of Reporting Trials guidelines for randomized controlled trials. Subjects were randomized into 2 groups as follows: open surgery and microendoscopic group. The outcomes included pain score, functional outcome, satisfaction rate, radiological outcomes, and complications. The statistical analyses in this study were performed using the Statistical Package for the Social Sciences 20.0 software. P < .05 was accepted as statistically significant. RESULTS: The hypothesis was that the open technique would achieve similar clinical outcomes as compared to the microendoscopic technique in LDH. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5708).

miR-27a promotion resulting from silencing of HDAC3 facilitates the recovery of spinal cord injury by inhibiting PAK6 expression in rats.

AIMS: Spinal cord injury (SCI) is one of the most devastating diseases that challenges neurology and medicine, leading to paraplegia or quadriplegia worldwide. Neuroprotection conferred by histone deacetylase (HDAC) inhibitors against various insults and deficits in the central nervous system has been reported previously. Herein, we set out to ascertain whether HDAC3 inhibition exerts neuroprotective effects against SCI. MAIN METHODS: A modified Allen's weight-drop method was performed to induce experimental SCI in rats. Basso-Beattie-Bresnahan (BBB) scores were used to assess locomotor function. Flow cytometric analysis of AnnexinV-FITC/PI double staining, TUNEL staining, and immunoblotting analysis of apoptosis-related proteins were performed to determine apoptosis in H2O2-induced cell injury of primary rat neurons. KEY FINDINGS: Upregulated HDAC3 and downregulated miR-27a were observed in spinal cord tissues of SCI rats and H2O2-injured neurons. HDAC3 knockdown by its specific shRNA restored the locomotor function of SCI rats and prevented rat neurons from H2O2-induced apoptosis through promotion of miR-27a. miR-27a targeted PAK6 (encoding P21-activated kinase 6) and inhibited its expression. The effects of HDAC3 knockdown on the locomotor function of SCI rats and H2O2-induced apoptosis of rat neurons were lost upon further PAK6 overexpression. SIGNIFICANCE: The present study uncovers that silencing HDAC3 inhibited PAK6 expression by upregulating miR-27a, eventually inhibiting neuron apoptosis and promoting the recovery of SCI, which might provide a novel therapeutic target for SCI.

Spinal cord extracts from injured spinal cord impede differentiation of rat embryonic neural stem cells into neurons through regulating Notch signaling pathway.

SCI (spinal cord injury) is a complex and serious neurological disease with no efficient treatment. NSC (neural stem cells) have the potential for self-renewal, proliferation and differentiation into all types of nerve cells. The aim of our study is to evaluate the effect of SCE (spinal cord extracts) from injured spinal cord on the differentiation of rat embryonic NSC and to clarify its potential mechanism. Here, NSC were isolated and cultured with SCE. The experiments were divided into four groups, including NSC + sham, NSC + SCE, NSC + SCE + DMSO (dimethyl sulfoxide), NSC + SCE + DAPT (N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-Phenyl-glycinet-butylester). The Notch1 (notch receptor 1) and Hes1 (hes family bHLH transcription factor 1) mRNA expression was analyzed by qPCR (quantitative real-time PCR) analysis. The protein expression levels of GFAP (glial fibrillary acidic protein) and NSE (nestin) were evaluated by immunofluorescence staining. Cell differentiation of NSC was induced by using neurobasal medium. The results showed that the NSC were successfully identified, and could proliferate to form spherical aggregates and was passaged continuously and steadily in vitro. The NSC at fifth generation were positively stained with NSE, and was capable of differentiating into NSE-positive cells and GFAP-positive cells. SCE treatment could upregulate the mRNA expression levels of Notch1 and Hes1, but inhibited the differentiation of NSC into neurons. DAPT could down-regulate the mRNA expression of Notch1 and Hes1 in NSC. Mechanically, DAPT targeting Notch signal pathway could facilitate NSC differentiation into neurons. Together, our data highlighted that SCE suppresses the differentiation of rat embryonic NSC by regulating the Notch signaling pathway, and DAPT treatment can reverse the effect of SCE related differentiation.

A novel hybrid fixation (percutaneous anterior pelvic bridge with K-wire) for the treatment of traumatic pelvic ring injury: A prospective study.

BACKGROUND: The aim of the study was to introduce a novel percutaneous technique for the treatment of pelvic ring injuries using a percutaneous anterior pelvic bridge (PAPB) with K-wire. METHODS: From December 2010 to November 2016, a prospective study of 86 patients with anterior pelvic ring fracture (42 utilizing PAPB with K-wire and 44 utilizing PAPB). Patient data was retrieved from electronic charts. Radiological results were assessed based on the Matta criteria system to evaluate the quality of the reduction and time to union. Functional outcomes were evaluated using the Majeed scoring system. Postoperative complications were also recorded. RESULTS: Age, sex, cause of injury, type of fracture, functional recovery, American Society of Anesthesiologists classification, union time, Majeed scoring and complications did not differ significantly between the two groups. The quality of the reduction and pain scoring differed between groups (all p-values < 0.05). Group A got better reduction and less pain scoring. CONCLUSIONS: The novel percutaneous technique with hybrid fixation using PAPB with K-wire is a successful alternative for the treatment of pelvic ring injuries, which results in better quality of reduction and less pain scoring outcomes comparing to PAPB. May the PAPB + K-wire could provide more stability.

Comparison of intrathecal and local infiltration analgesia by morphine for pain management in total knee and hip arthroplasty: A meta-analysis of randomized controlled trial.

OBJECTIVE: We performed a meta-analysis from randomized controlled trials to evaluate the efficiency and safety between local infiltration analgesia and intrathecal morphine for pain control in total knee and hip arthroplasty. METHODS: We systemically searched electronic databases including Embase (1980-2016.7), Medline (1966-2016.7), PubMed (1966-2016.7), ScienceDirect (1985-2016.7), web of science (1950-2016.7) and Cochrane Library for relevant articles. All calculation was carried out by Stata 11.0. RESULTS: Four randomized controlled trials (RCTs) involving 242 patients met the inclusion criteria. The meta-analysis showed that there were significant differences in terms of postoperative pain scores at 24 h during rest (P = 0.008) and mobilization (P = 0.049) following total knee and hip arthroplasty. Significant difference was found regarding the incidence of nausea (P = 0.030), vomiting (P = 0.005), and pruritus (P = 0.000) between two groups. There was no significant difference between groups in terms of morphine equivalent consumption at postoperative 24 or 48 h. CONCLUSIONS: Local infiltration analgesia (LIA) provided superior analgesic effects within the first 24 h compared to intrathecal morphine (ITM) following total knee and hip arthroplasty. There were fewer adverse effects in LIA. Doses of morphine consumption were similar in the two groups.

ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro.

Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway.

Tranexamic Acid Reduces Hidden Blood Loss in Patients Undergoing Total Knee Arthroplasty: A Comparative Study and Meta-Analysis.

BACKGROUND: To explore the efficacy of tranexamic acid (TXA) on reducing hidden blood loss (HBL) in total knee arthroplasty (TKA) by conducting a comparative study and meta-analysis. MATERIAL/METHODS: A total of 108 patients underwent TKA was equally distributed to experimental and control groups. The only difference between two groups was the administrations of 15 mg of TXA mixed in 100 mL normal saline for experimental group and 100 mL of normal saline for control group. The volumes of blood loss, red blood loss (RBL) were recorded, calculated and analyzed. Stata 12.0 software was applied for data analysis. RESULTS: The intraoperative and postoperative blood loss volume in experimental group were remarkably reduced compared with those in control group (intraoperative: 105.1±12.1 mL vs. 185.5±20.3 mL, P<0.001; postoperative: 220.7±16.8 mL vs. 290.5±22.4 mL, P<0.001). Accordingly, the control group had significantly higher transfusion rate than experimental group (3.7% vs.25.9%, P=0.001). Our results also found that both the measured and hidden RBL were obviously reduced in experimental group compared with control group (measured RBL: 96.9±11.8 mL vs. 135.2±13.5 mL, P<0.001; hidden RBL: 170.8±37.2 mL vs. 364.2±41.5 mL, P<0.001). Furthermore, meta-analysis confirmed that TXA can notably decrease HBL (SMD=2.68, 95%CI=1.55~3.80, P<0.001). CONCLUSIONS: TXA can significantly reduce the intraoperative and postoperative blood loss and HBL, therefore decreasing the transfusion need in TKA.

Effect of spinal cord extracts after spinal cord injury on proliferation of rat embryonic neural stem cells and Notch signal pathway in vitro.

OBJECTIVE: To investigate the effect of the spinal cord extracts (SCE) after spinal cord injuries (SCIs) on the proliferation of rat embryonic neural stem cells (NSCs) and the expressions of mRNA of Notch1 as well as of Hes1 in this process in vitro. METHODS: The experiment was conducted in 4 different mediums: NSCs+PBS (Group A-blank control group), NSCs+SCE with healthy SD rats (Group B-normal control group), NSCs+SCE with SD rats receiving sham-operation treatment (Group C-sham-operation group) and NSCs+ SCE with SCIs rats (Group D-paraplegic group). Proliferative abilities of 4 different groups were analyzed by MTT chromatometry after co-culture for 1, 2, 3, 4 and 5 d, respectively. The expressions of Notch1 and Hes1 mRNA were also detected with RT-PCR after co-culture for 24 and 48 h, respectively. RESULTS: After co-culture for 1, 2, 3, 4 and 5 d respectively, the MTT values of group D were significantly higher than those of group A, group B and group C (P<0.05). However, there were no significantly differences regarding MTT values between group A, group B and group C after co-culture for 1, 2, 3, 4 and 5 d, respectively (P>0.05). Both the expressions of Notch1 and Hes1 mRNA of group D were significantly higher than those of other 3 groups after co-culture for 24 h and 48 h as well (P<0.05). But there was no difference oin expressions of Notch1 and Hes1 mRNA among group A, group B and group C after co-culture for 24 h and 48 h (P>0.05). There was no difference in expressions of Notch1 and Hes1 mRNA between 24 h and 48 h treatment in group D. CONCLUSIONS: SCE could promote the proliferation of NSCs. It is demonstrated that the microenvironment of SCI may promote the proliferation of NSCs. Besides, SCE could increase the expression of Notch1 and Hes1 mRNA of NSC. It can be concluded that the Notch signaling pathway activation is one of the mechanisms that locally injured microenvironment contributes to the proliferation of ENSC after SCIs. This process may be performed by up-regulating the expressions of Notch1 and Hes1 gene.