Xianhu Zhou

Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up.

Schwann cells (SCs) are the main glial cells of the peripheral nervous system, which can promote neural regeneration. Grafting of autologous SCs is one of the well-established and commonly performed procedures for peripheral nerve repair. With the aim to improve the clinical condition of patients with spinal cord injury (SCI), a program of grafting autologous activated Schwann cells (AASCs), as well as a series of appropriate neurorehabilitation programs, was employed to achieve the best therapeutic effects. We selected six patients who had a history of SCI before transplantation. At first, AASCs were obtained by prior ligation of sural nerve and subsequently isolated, cultured, and purified in vitro. Then the patients accepted an operation of laminectomy and cell transplantation, and no severe adverse event was observed in any of these patients. Motor and sensitive improvements were evaluated by means of American Spinal Injury Association (ASIA) grading and Functional Independence Measure (FIM); bladder and urethral function were determined by clinical and urodynamic examination; somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were used to further confirm the functional recovery following transplantation. The patients were followed up for more than 5 years. All of the patients showed some signs of improvement in autonomic, motor, and sensory function. So we concluded that AASC transplantation might be feasible, safe, and effective to promote neurorestoration of SCI patients.

An Experimental Novel Study: Angelica sinensis Prevents Epidural Fibrosis in Laminectomy Rats via Downregulation of Hydroxyproline, IL-6, and TGF-β1

With laminectomy being widely accepted as the treatment for lumbar disorders, epidural fibrosis (EF) is a common complication for both the patients and the surgeons alike. Currently, EF is thought to cause recurrent postoperative pain after laminectomy or after discectomy. Angelica sinensis is a traditional Chinese medicine which has shown anti-inflammatory, antifibrotic, and antiproliferative properties. The object of this study was to investigate the effects of Angelica sinensis on the prevention of post-laminectomy EF formation in a rat model. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. They were divided randomly into 3 groups according to the treatment method, with 20 in each group: (1) Angelica sinensis treatment group, (2) saline treatment group, and (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks after laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density, and inflammatory factors expressions all suggested better results in Angelica sinensis group than the other two groups. Topical application of Angelica sinensis could inhibit fibroblasts proliferation and TGF-β1 and IL-6 expressions and prevent epidural scar adhesion in postlaminectomy rat model.

Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal tunnel syndrome: A systematic review and meta-analysis

Background:Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disease. Either surgical or conservative intervention for CTS patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical efficacy, safety, and cost of surgical versus nonsurgical intervention. Methods:The eligible studies were acquired from PubMed, Medline, Embase, Web of Science, Google, and Cochrane Library. The data were extracted by 2 of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess risk of bias. Results:Thirteen studies including 9 randomized controlled trials (RCTs) and 4 observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The difference of clinical efficacy was statistically significant between surgical and nonsurgical intervention, and nonsurgical treatment was more effective (OR = 2.35, 95%CI = 1.18–4.67, P = 0.01). Meanwhile, different results were discovered by subgroup analysis. The pooled results of function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care at different follow-up times showed that the differences were not statistically significant between the 2 interventions. The difference of complications and side-effects was statistically significant and conservative treatment achieved better result than surgery (OR = 2.03, 95%CI = 1.28–3.22, P = 0.003). Sensitivity analysis proved the stability of the pooled results. Conclusion:Both surgical and conservative interventions had benefits in CTS. Nonsurgical treatment was more effective and safety than surgical treatment, but there were no significant differences in function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care. Nonsurgical treatment is recommended as the optical choice for CTS. If conservative treatment fails, surgical release can be taken.Supplemental Digital Content is available in the text

Identification of microRNAome in rat bladder reveals miR-1949 as a potential inducer of bladder cancer following spinal cord injury

The costs of spinal cord injury and its complications are high in personal, social and financial terms. Complications include bladder cancer, for which the risk is 16-28 times higher than that of the general population, There is currently little consensus regarding the cause of this discrepancy. As microRNAs are stable biomarkers and potential therapeutic targets of cancer, the present study aimed to explore the underlying mechanisms of this phenomenon by examining changes in the microRNAome. Rats were used to produce models of spinal cord injury. Microarrays and bioinformatics were used to investigate the cancer-associated microRNAs that are upregulated in rat bladders following spinal cord injury. In order to validate the results, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were performed. The expression of miR-1949 was found to be deregulated and abundant in the rat bladder following spinal cord injury. Bioinformatics demonstrated that retinoblastoma 1, which is involved in tumorigenesis, is a target gene of miR-1949. qRT-PCR, western blotting and immunohistochemistry confirmed the results of the microarray analysis. In addition, it was shown that miR-1949 expression was not influenced by aging. Furthermore, the expression of miR-1949 was stable until the third month following spinal cord injury, after which it significantly increased. If this increase was prolonged, the expression of retinoblastoma 1 may decline to a carcinogenic level. The present study suggests a role for miR-1949 in the translational regulation of retinoblastoma 1 and in subsequent bladder tumorigenesis following spinal cord injury.

Efficacy and safety of triamcinolone acetonide alone and in combination with 5-fluorouracil for treating hypertrophic scars and keloids: a systematic review and meta-analysis

Pathological scars, such as keloids and hypertrophic scars, readily cause physical and psychological problems. Combination 5‐fluorouracil (5‐FU) with triamcinolone acetonide (TAC) is presumed to enhance the treatment of pathological scars, although supportive evidence is lacking. We aimed to compare the efficacy and safety of TAC alone and in combination with 5‐FU for the treatment of hypertrophic scars and keloids. Five databases (PubMed, Medline, Cochrane databases, Embase and CNKI) were searched with the limitations of human subjects and English‐language text. Mean differences (MDs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Cochrane Collaborations Risk of Bias Tool was used to assess the risk of bias. The control group received intralesional TAC alone, and the experimental group received TAC combined with 5‐FU injection. A pooled analysis of the effectiveness based on patient self‐assessment after treatment showed that the experimental group achieved better results than the control group (OR = 2·92, 95% CI = 1·63–5·22, P = 0·0003). Similarly, a pooled analysis of the effectiveness based on observer assessment following treatment produced the same conclusion (OR = 4·03, 95% CI = 1·40–11·61, P = 0·010). A meta‐analysis of scar height after treatment showed that the experimental group performed better than the control group (MD = −0·14, 95% CI = −0·23–0·05, P = 0·002). The erythema score of the experimental group after treatment was superior (MD = −0·20, 95% CI = −0·34–0·06, P = 0·004). The heterogeneity test showed no heterogeneity among the studies (P > 0·1, I2 = 0%). TAC combined with 5‐FU is more suitable for the treatment and prevention of hypertrophic scars and keloids, with greater improvement in scar height and patient satisfaction as well as fewer side effects.

Comparison of DNA Methylation in Schwann Cells before and after Peripheral Nerve Injury in Rats

This study aims to find the difference of genomewide DNA methylation in Schwann cells (SCs) before and after peripheral nerve system (PNS) injury by Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq) and seek meaningful differentially methylated genes related to repairment of injured PNS. SCs harvested from sciatic nerve were named as activated Schwann cells (ASCs), and the ones harvested from brachial plexus were named as normal Schwann cells (NSCs). Genomic DNA of ASCs and NSCs were isolated and MeDIP-Seq was conducted. Differentially methylated genes and regions were discovered and analyzed by bioinformatic methods. MeDIP-Seq analysis showed methylation differences were identified between ASCs and NSCs. The distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in distal intergenic regions. GO and KEGG analysis of these methylated genes were also conducted. The expression patterns of hypermethylated genes (Dgcr8, Zeb2, Dixdc1, Sox2, and Shh) and hypomethylated genes (Gpr126, Birc2) detected by qRT-PCR were opposite to the MeDIP analysis data with significance (p < 0.05), which proved MeDIP analysis data were real and believable. Our data serve as a basis for understanding the injury-induced epigenetic changes in SCs and the foundation for further studies on repair of PNS injury.

Efficacy and safety of tension band wiring versus plate fixation in olecranon fractures: a systematic review and meta-analysis.

BackgroundOlecranon fracture (OF) is a common upper limb fracture, and the most commonly used techniques are still tension band wiring (TBW) and plate fixation (PF). The aim of the current study is to discuss whether TBW or PF technique of internal fixation is better in the treatment of OFs, using the method of meta-analysis.MethodsThe eligible studies were acquired from PubMed, CNKI, Embase, Cochrane Library, and other sources. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration’s Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess risk of bias.ResultsThirteen studies including 1 RCT and 12 observational studies were assessed. Our meta-analysis results showed that both in RCT and observational studies, there were no significant differences between the two groups in disabilities of the arm, shoulder and hand (DASH) (SMD = 0.07, 95% CI = −0.32 to 0.46, p = 0.73), improvement rate (OR = 0.76, 95% CI = 0.48–1.22, p = 0.26), range of motion (ROM), operation time (SMD = −0.51, 95% CI = −1.17 to 0.14, p = 0.12) and blood loss (SMD = −0.97, 95% CI = −2.06 to 0.11, p = 0.08). The overall estimate of complications indicated that the pooled OR was 2.61 (95% CI = 1.65–4.14, p < 0.0001), suggesting that the difference was statistically significant. We also compared the outcomes of patients with mayo type IIA OFs treated by TBW and PF in DASH and ROM and found no differences.ConclusionsBoth TBW and PF interventions had treatment benefit in OFs. The current study reveals that there are no significant differences in DASH, improvement rate, ROM, operation time, and blood loss between TBW and PF for OFs. Due to the less complications, we recommend the PF approach as the optical choice for OFs. More high-quality studies are required to further confirm our results.

Does local lavage influence functional recovery during lumber discectomy of disc herniation?: One year's systematic follow-up of 410 patients.

AbstractLumbar disc herniation (LDH) is a common disease and lumbar discectomy is the most common surgical procedure carried out for patients with low back pain and leg symptoms. Although most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the effect of local intervertebral lavage during microdiscectomy.In this retrospective study, 410 patients were operated on by microdiscectomy for LDH during 2011 to 2014. Retrospectively, 213 of them (group A) accepted local intervertebral irrigation with saline water before wound closure and 197 patients (group B) only had their operative field irrigated with saline water. Systematic records of visual analog scores (VAS), Oswestry disability Index (ODI) questionnaire scale scores, use of analgesia, and hospital length of stay were done after hospitalization.The majority (80.49%) of the cases were diagnosed with lumber herniation at the levels of L4/5 and L5/S1. Fifty-one patients had herniations at 2 levels. There were significant decreases of VAS scores and ODI in both groups between preoperation and postoperation of different time points. VAS scores decreased more in group A than group B at early stage of postoperation follow-up. However, there were no statistically significant differences between 2 groups in using analgesia, VAS and ODI up to 1 month of follow-up.Microdiscectomy for LDH offers a marked improvement in back and radicular pain. Local irrigation of herniated lumber disc area could relief dick herniation-derived low back pain and leg radicular pain at early stage of post-operation. However, the pain relief of this intervention was not noticeable for a long period.

Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury

Background Spinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI. Purpose In this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI. Patients and methods Polycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation. Results The iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds werê0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model. Conclusion This study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future.

Microenvironment Imbalance of Spinal Cord Injury

Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, ‘microenvironment imbalance’ is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue’s level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.