Estradiol protects female mice from hyperuricemia induced by PCB138 exposure.

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5-50 µg/kg bw PCB138 during postnatal days (PND) 3-21 led to elevated serum uric acid (UA) levels and kidney injury in adult male mice. Given that the prevalence of hyperuricemia (HUA) is significantly lower in women than in men, it is worth investigating whether POP-induced HUA and its secondary kidney injury have sexual dimorphism. Herein, we exposed female mice to 0.5-50 µg/kg bw PCB138 during PND 3-21, resulting in elevated serum UA levels, but without causing significant kidney damage. Concurrently, we found a negative correlation between serum 17ß-estradiol (E2) and serum UA levels. We also observed down-regulation of estrogen receptor (ER) protein levels in the kidneys of the PCB138-exposed groups. Furthermore, our study showed that E2 rescued the increased UA level and cytotoxicity caused by HUA in human renal tubular epithelial (HK-2) cells. Collectively, our findings suggest that E2 likely plays a crucial protective role in PCB138-induced HUA and kidney injury in female mice. Our research highlights the existence of sexual dimorphism in kidney injury secondary to HUA induced by POPs, which could provide guidance for individuals of different genders in preventing kidney injury caused by environmental factors.

Alternative splicing and alternative polyadenylation define tumor immune microenvironment and pharmacogenomic landscape in clear cell renal carcinoma.

Two major posttranscriptional mechanisms-alternative splicing (AS) and alternative polyadenylation (APA)-have attracted much attention in cancer research. Nevertheless, their roles in clear cell renal carcinoma (ccRCC) are still ill defined. Herein, this study was conducted to uncover the implications of AS and APA events in ccRCC progression. Through consensus molecular clustering analysis, two AS or APA RNA processing phenotypes were separately constructed with distinct prognosis, tumor-infiltrating immune cells, responses to immunotherapy, and chemotherapy. The AS or APA score was constructed to quantify AS or APA RNA processing patterns of individual ccRCCs with principal-component analysis. Both high AS and APA scores were characterized by undesirable survival outcomes, relatively high response to immunotherapy, and low sensitivity to targeted drugs, such as sorafenib and pazopanib. Moreover, several small molecular compounds were predicted for patients with a high AS or APA score. There was a positive correlation between AS and APA scores. Their interplay contributed to poor prognosis and reshaped the tumor immune microenvironment. Collectively, this study is the first to comprehensively analyze two major posttranscriptional events in ccRCC. Our findings uncovered the potential functions of AS and APA events and identified their therapeutic potential in immunotherapy and targeted therapy.

Characterization of Molecular Heterogeneity Associated With Tumor Microenvironment in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and has strong immunogenicity. A systematically investigation of the tumor microenvironment (TME) in ccRCC could contribute to help clinicians develop personalized treatment and facilitate clinical decision-making. In this study, we analyzed the immune-related subtype of ccRCC on the basis of immune-related gene expression data in The Cancer Genome Atlas (TCGA, N = 512) and E-MTAB-1980 (N = 101) dataset, respectively. As a result, two subtypes (C1 and C2) were identified by performing non-negative matrix factorization clustering. Subtype C1 was characterized by increased advance ccRCC cases and immune-related pathways. A higher immune score, stromal score, TMB value, Tumor Immune Dysfunction and Exclusion (TIDE) prediction score, and immune checkpoint genes expression level were also observed in C1. In addition, the C1 subtype might benefit from chemotherapy and immunotherapy. The patients in subtype C2 had more metabolism-related pathways, higher tumor purity, and a better prognosis. Moreover, some small molecular compounds for the treatment of ccRCC were identified between the two subtypes by using the Connectivity Map (CMap) database. Finally, we constructed and validated an immune-related (IR) score to evaluate immune modification individually. A high IR score corresponded to a favorable prognosis compared to a low IR score, while more advanced tumor stage and grade cases were enriched in the low IR score group. The two IR score groups also showed a distinct divergence among immune status, TME, and chemotherapy. The external validation dataset (E-MTAB-1980) and another immunotherapy cohort (IMvigor 210) demonstrated that patients in the high IR score group had a significantly prolonged survival time and clinical benefits compared to the low IR score group. Together, characterization of molecular heterogeneity and IR signature may help develop new insights into the TME of ccRCC and provide new strategies for personalized treatment.

Characterization of Hypoxia-Related Molecular Subtypes in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy and Targeted Therapy via Multi-Omics Analysis.

Objective: Tumor hypoxia is a key factor in resistance to anti-cancer treatment. Herein, this study aimed to characterize hypoxia-related molecular subtypes and assess their correlations with immunotherapy and targeted therapy in clear cell renal cell carcinoma (ccRCC). Materials: We comprehensively analyzed copy number variation (CNV), somatic mutation, transcriptome expression profile and clinical information for ccRCC from TCGA and ICGC databases. Based on 98 prognosis-related hypoxia genes, samples were clustered using unsupervized non-negative matrix factorization (NMF) analysis. We characterized the differences between subtypes concerning prognosis, CNV, somatic mutations, pathways, immune cell infiltrations, stromal/immune scores, tumor purity, immune checkpoint inhibitors (ICI), response to immunotherapy and targeted therapy and CXC chemokines. Based on differentially expressed genes (DEGs) between subtypes, a prognostic signature was built by LASSO Cox regression analysis, followed by construction of a nomogram incorporating the signature and clinical features. Results: Two hypoxia-related molecular subtypes (C1 and C2) were constructed for ccRCC. Differential CNV, somatic mutations and pathways were found between subtypes. C2 exhibited poorer prognosis, higher immune/stromal scores, and lower tumor purity than C1. Furthermore, C2 had more sensitivity to immunotherapy and targeted therapy than C1. The levels of CXCL1/2/3/5/6/8 chemokines in C2 were distinctly higher than in C1. Consistently, DEGs between subtypes were significantly enriched in cytokine-cytokine receptor interaction and immune responses. This subtype-specific signature can independently predict patients' prognosis. Following verification, the nomogram could be utilized for personalized prediction of the survival probability. Conclusion: Our findings characterized two hypoxia-related molecular subtypes for ccRCC, which can assist in identifying high-risk patients with poor clinical outcomes and patients who can benefit from immunotherapy or targeted therapy.

Development and Validation of Nine-RNA Binding Protein Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma.

Cumulative studies have shown that RNA binding proteins (RBPs) play an important role in numerous malignant tumors and are related to the occurrence and progression of tumors. However, the role of RBPs in kidney renal clear cell carcinoma (KIRC) is not fully understood. In this study, we first downloaded gene expression data and corresponding clinical information of KIRC from the Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) database, respectively. A total of 137 differentially expressed RBPs (DERBPs) were then identified between normal and tumor tissue, including 38 downregulated and 99 upregulated RBPs. Nine RBPs (EIF4A1, RPL36A, EXOSC5, RPL28, RPL13, RPS19, RPS2, EEF1A2, and OASL) were served as prognostic genes and exploited to construct a prognostic model through survival analysis. Kaplan-Meier curves analysis showed that the low-risk group had a better survival outcome when compared with the high-risk group. The area under the curve (AUC) value of the prognostic model was 0.713 in the TCGA data set (training data set), 0.706 in the ICGC data set, and 0.687 in the GSE29609 data set, respectively, confirming a good prognostic model. The prognostic model was also identified as an independent prognostic factor for KIRC survival by performing cox regression analysis. In addition, we also built a nomogram relying on age and the prognostic model and internal validation in the TCGA data set. The clinical benefit of the prognostic model was revealed by decision curve analysis (DCA). Gene set enrichment analysis revealed several crucial pathways (ERBB signaling pathway, pathways in cancer, MTOR signaling pathway, WNT signaling pathway, and TGF BETA signaling pathway) that may explain the underlying mechanisms of KIRC. Furthermore, potential drugs for KIRC treatment were predicted by the Connectivity Map (Cmap) database based on DERBPs, including several important drugs, such as depudecin and vorinostat, that could reverse KIRC gene expression, which may provide reference for the treatment of KIRC. In summary, we developed and validated a robust nine-RBP signature for KIRC prognosis prediction. A nomogram with risk score and age can be applied to promote the individualized prediction of overall survival in patients with KIRC. Moreover, the two drugs depudecin and vorinostat may contribute to KIRC treatment.

USP22 promotes proliferation in renal cell carcinoma by stabilizing survivin.

Renal cell carcinoma (RCC) is one of the commonest urological tumors. The incidence of RCC ranks third among urological tumors, after prostate cancer and bladder tumors. However, the etiology of RCC remains unclear. Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, is associated with the occurrence and progression of numerous tumors. However, the roles of USP22 in RCC have not yet been investigated. Survivin is a member of the inhibitor of apoptotic protein family involved in RCC progression. The present study first detected the expression of USP22 and survivin in RCC tissues using immunohistochemistry and western blotting. It was revealed that the protein levels of USP22 and survivin in RCC tissues were higher than those in adjacent normal renal tissue. Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved-caspase-3. By contrast, overexpression of USP22 promoted the growth of ACHN cells, upregulated the expression of survivin and decreased the level of cleaved-caspase-3. Notably, the changes in USP22 expression did not affect the SURVIVIN mRNA level. Finally, it was confirmed that USP22 interacted with survivin and stabilized it by downregulating its ubiquitination. The present results indicate that USP22 may regulate survivin via deubiquitination, thereby promoting the proliferation of RCC cells. The results of the current study suggest that USP22 may represent a novel therapeutic target for patients with RCC.

Identification of 12 immune-related lncRNAs and molecular subtypes for the clear cell renal cell carcinoma based on RNA sequencing data.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). Despite the existing extensive research, the molecular and pathogenic mechanisms of ccRCC are elusive. We aimed to identify the immune-related lncRNA signature and molecular subtypes associated with ccRCC. By integrating 4 microarray datasets from Gene Expression Omnibus database, we identified 49 immune-related genes. The corresponding immune-related lncRNAs were further identified in the TCGA dataset. 12-lncRNAs prognostic and independent signature was identified through survival analysis and survival difference between risk groups was further identified based on the risk score. Besides, we identified 3 molecular subtypes and survival analysis result showed that cluster 2 has a better survival outcome. Further, ssGSEA enrichment analysis for the immune-associated gene sets revealed that cluster 1 corresponded to a high immune infiltration level. While cluster 2 and cluster 3 corresponded to low and medium immune infiltration level, respectively. In addition, we validated the 12-lncRNA prognostic signature and molecular subtypes in an external validation dataset from the ICGC database. In summary, we identified a 12-lncRNA prognostic signature which may provide new insights into the molecular mechanisms of ccRCC and the molecular subtypes provided a theoretical basis for personalized treatment by clinicians.

The preliminary efficacy evaluation of the CTLA-4-Ig treatment against Lupus nephritis through in-silico analyses.

The humanized cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA-4-Ig) has been used to treat Lupus nephritis (LN) based on CTLA-4s negative regulation of T-cell activation through competent to binding with CD80/CD86, the inherent genetic factors influencing the CTLA-4-Ig treatment efficacy are widely unknown. Here, 62 nonsynonymous single nucleotide variants (nsSNVs) of CTLA-4 gene, 184 of CD80 and 201 of CD86 were identified and validated within both EMBL-EBI and dbSNP databases. Next, the nsSNVs rs1466152724 in CTLA-4, rs1196816748, rs765515058, rs1157880125, rs1022857991, and rs142547094 in CD80 and rs1203132714 in CD86 were consistently suggested to be deleterious by SIFT, PolyPhen-2, PROVEAN and meta LR. Based on the 3D structure stability analysis, the variant rs765515058 causing G167V in CD80 was found to reduce the protein's stability through changing the characters of constructed structure of complete CD80 apo form and stabilizing amino acid residues of CD80 holo form in a great degree. Furthermore, the interaction energy analysis results suggested that rs1022857991 causing C50F may reduce the binding energy of CTLA-4 with CD80. Along with the increasing variants, these nsSNVs' effects on the interaction of CTLA-4 with CD80/CD86 will increase, and thus influence the CTLA-4-Ig treatment efficacy against LN.

Arthroscopic techniques and instruments for meniscal allograft transplantation using the bone bridge in trough method.

The aim of the current study was to investigate the construction of the bone bridge and tibial plateau under arthroscopy during meniscal allograft transplantation, in order to simplify and enhance the accuracy of bone bridge fixation intraoperatively. A traction line passed through the attachment of the anterior and posterior horns of the superior meniscus to the bone bridge was used to pull the bone bridge into the knee joint cavity and fix the anteroposterior horns of the meniscus. At the junction of the body of the meniscus and the posterior and anterior horns of the meniscus, a traction line was created at the anterior and posterior 1/3 of the meniscus to pull and fix the meniscus. Under the arthroscope, the aiming device was placed on the tibial plateau. The direction and width of the guide plate were identical to those of the bone trough of the tibial plateau. The bone tunnel was made using the guide needle and a 9-mm hollow drill, the piston rod was inserted, and the arch-shaped bone knife was inserted along with the piston rod to construct the 9-mm bone trough of the tibial plateau. The periphery of the meniscus was sutured to the joint capsule. These surgical techniques and instruments could standardize meniscal graft transplantation and avoid the incidence of surgical errors caused by mismatched size and shape of the bone bridge and bone trough. This would make the surgery more convenient, safe and accurate. The four-point fixation of the tibial plateau contributed to preventing the reversal of the meniscus during transplantation, and partially reconstructed the coronary ligament of the meniscal tibia, which probably enhanced the stability of the meniscus and minimized the risk of extrusion of the meniscal allograft. The bone bridge and bone trough of the tibial plateau were properly constructed under arthroscopy. Dynamic monitoring of surgical indications, explicit preoperative preparation and standardized surgical procedures could achieve high efficacy and excellent fixation effect during meniscal graft transplantation. The four-point fixation of the tibial plateau maintains and enhances the stability of the meniscal allograft, reduces the risk of meniscal extrusion and ensures the postoperative recovery of meniscal function.

Development of a Rat Model of Sick Sinus Syndrome Using Pinpoint Press Permeation.

OBJECTIVE: Sick sinus syndrome (SSS) is one of the most common causes of cardiac impairment necessitating pacemaker implantation. However, studies of SSS pathogenesis are neither comprehensive nor conclusive due to limited success in achieving a stable rat SSS model. Here, we modified pinpoint press permeation to establish a stable rat SSS model. METHODS: We randomly assigned 138 male Sprague-Dawley rats into three groups: normal control (n = 8), sham (n = 10), and SSS (n = 120). Postoperatively, the SSS group was further divided into SSSA (n = 40), SSSB (n = 40), and SSSC (n = 40), based on reduction in heart rates by 20-30%, 31-40%, and 41-50%, respectively. We also assessed histomorphological characteristics and hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) expression in the sinoatrial node (SAN) at 1, 2, 3, and 4 weeks after surgery. RESULTS: Mortality was statistically higher in SSSC compared to SSSA and SSSB (7.5% versus 90.0% and 87.5%; P < 0.05). Heart rate in SSSA was gradually restored to preoperative levels by week 4 after surgery. In contrast, heart rate in SSSB was stable at 2-3 weeks after surgery. However, we observed that the tissues and cells in SAN were severely injured and also found a time-dependent increase in collagen content and atrium myocardium in SSSB. HCN4 expression was significantly reduced at all 4 time points in SSSB, with statistically significant differences among the groups (P < 0.01). CONCLUSION: We successfully developed a rat SSS model that was sustainable for up to 4 weeks.

A nanohybrid composed of Prussian Blue and graphitic C3N4 nanosheets as the signal-generating tag in an enzyme-free electrochemical immunoassay for the neutrophil gelatinase-associated lipocalin.

An enzyme-free electrochemical immunoassay is described for the neutrophil gelatinase-associated lipocalin (NGAL; a biomarker of kidney disease). Prussian Blue (PB) nanoparticles with redox activity were deposited on graphitic C3N4 nanosheets (g-C3N4) by in-situ reduction. A screen printed electrode (SPCE) was modified with antibody against NGAL, and the PB-g-C3N4 nanohybrid was used as the signal-generating tag for the secondary antibody against NGAL. Upon addition of target NGAL and of secondary antibody, a sandwich is formed on the SPCE. At an applied potential of typically 0.13 V (vs. Ag/AgCl), a well-defined voltammetric peak is observed that results from the presence of PB on the secondary antibody. Under optimal conditions, the peak current increases linearly in the 0.01 to 10 ng·mL-1 NGAL concentration range, and the detection limit is 2.8 pg·mL-1. An average precision of <12% was accomplished in the batch-to-batch mode. Other disease-related biomarkers do not interfere. The accuracy and inter-laboratory validation of this method were evaluated for target NGAL detection in spiked human serum by using a commercial ELISA. The results obtained by the two methods are in good accordance. Graphical abstract An enzyme-free electrochemical immunoassay was used for detection of neutrophil gelatinase-associated lipocalin by Prussian blut/graphitic-C3N4 nanohybrids as the signal-generation tags.

Expression of minichromosome maintenance genes in renal cell carcinoma.

Minichromosome maintenance (MCM) proteins play an essential role in DNA replication. They have been shown to be overexpressed in various types of cancer. However, the role of this family in renal cell carcinoma (RCC) is widely unknown. In this study, we have identified a number of RCC datasets in the Gene Expression Omnibus database and also investigated the correlation between the expression levels of MCM genes and clinicopathological parameters. We found that the expression levels of MCM genes are positively correlated with one another. Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were higher in RCC compared to paired adjacent normal tissue. Only the expression level of MCM4, but not of other MCMs, was positively correlated with tumor grade. In addition, a high-level expression of MCM2 in either primary tumor or metastases of RCC predicted a shorter disease-free survival time, while a high-level expression of MCM4 or MCM6 in primary tumor was also associated with poorer disease-free survival. Interestingly, we also demonstrated that patients with their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free survival time, while those with RCC metastases overexpressing 3 or more MCM genes had a shorter disease-free survival. Importantly, we also demonstrated that overexpression of MCM genes is an independent predictor for survival in RCC patients. Our results suggest that MCM2-7 genes may be an important prognostic marker for patients with RCC.

Properties and Osteogenicity of Two Calcium Sulfate Materials with Micro or Nano Morphology.

Calcium sulfate dihydrate (CaSO4 x 2H2O, CSD) was widely used as the artificial bone graft. In this study, two kinds of CSD materials were characterized with XRD, TG/DTA, FT-IR, and SEM. They were both composed of CSD. Spherical shape particles were observed for nano-CSD with diameters of 52-300 nm. The micro-CSD were thin sheet particles with dimensions of 5-10 µm. At 56 days post-implantation in vivo, nano-CSD had good tissue compatibility. A frequently used bioactive material DBM, which was the combination of nano-CSD (nano-CSD-DBM) and micro-CSD (micro-CSD-DBM) in a 1:1 weight ratio separately. Composite materials were implanted in intramuscular pockets in nude mouse model. New bone mineralization could be both observed in the surgery site. Collagen I was also widely distributed by immunohistochemistry assay. And new bone area of nano-CSD-DBM was 28 ± 4.6% at 4 weeks post-operation. But new bone area of micro-CSD-DBM was 16 ± 3.7% (less than nano-CSD-DBM). Nano-CSD showed increased degradation rate with obvious anginogenicity. And nano-CSD-DBM showed more excellent bone induction property as bone substitute implant.

Segmental anterior cervical corpectomy and fusion with preservation of middle vertebrae in the surgical management of 4-level cervical spondylotic myelopathy.

PURPOSE: To compare perioperative parameters, clinical outcomes, radiographic parameters, and complication rates of segmental anterior cervical corpectomy and fusion (sACCF) plus preservation of middle vertebrae with those of cervical laminectomy plus fusion (CLF) in 67 patients with 4-level cervical spondylotic myelopathy (CSM). METHODS: Between July 2006 and May 2012, 67 consecutive patients [42 males and 25 females; mean age 57.8 years (range 34-77 years)] with 4-level CSM who underwent surgery and were followed for more than 1 year were enrolled in this study and divided into sACCF and CLF groups. The study compared perioperative parameters; surgery-related and instrumentation- and graft-related complication rates; clinical parameters; patient satisfaction; and radiologic parameters. RESULTS: Significant improvements were seen from preoperative to postoperative in both groups for all three measures of clinical outcome; between-group comparison revealed no significant difference for two of the three measures and significantly better scores for the CLF group in the third. Satisfaction was rated as excellent or good by 79.5 % of the sACCF group and 71.4 % of the CLF group, which was not a significant difference. Mean postoperative cervical lordosis was significantly greater in the sACCF group than in the CLF group. Blood loss and operative time were significantly greater in the CLF group than in the sACCF group and complication rate significantly lower for the sACCF group. CONCLUSIONS: sACCF with preservation of middle vertebrae is a safe, reliable, and effective alternative procedure for the treatment of 4-level CSM.

Clinical and radiologic comparison of dynamic cervical implant arthroplasty versus anterior cervical discectomy and fusion for the treatment of cervical degenerative disc disease.

This study compared the clinical and radiological outcomes of dynamic cervical implant (DCI; Scient'x, Villers-Bretonneux, France) arthroplasty versus anterior cervical discectomy and fusion (ACDF) for the treatment of cervical degenerative disc disease. This prospective cohort study enrolled patients with single-level cervical degenerative disc disease who underwent DCI arthroplasty or ACDF between September 2009 and June 2011. Patients were followed up for more than 2years. Clinical evaluation included the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Neck Disability Index (NDI), Japan Orthopedic Association (JOA) score, and visual analog scale (VAS) scores for neck and arm pain. Radiological assessments included segmental range of motion (ROM), overall ROM (C2-C7), disc height (DHI), and changes in adjacent disc spaces. The VAS, SF-36, JOA, and NDI scores improved significantly after surgery in both the DCI and ACDF groups. The VAS, JOA, and SF-36 scores were not significantly different between the DCI and ACDF groups at the final follow-up. The segmental ROM at the treated level and overall ROM increased significantly after surgery in the DCI group, but the ROM in the adjacent cephalad and caudal segments did not change significantly. The mean DHI at the treated level was significantly restored after surgery in both groups. Five patients (12.8%) in the DCI group showed new signs of adjacent segment degeneration. These results indicate that DCI is an effective, reliable, and safe procedure for the treatment of cervical degenerative disc disease. However, there is no definitive evidence that DCI arthroplasty has better intermediate-term results than ACDF.

Exome sequencing on malignant meningiomas identified mutations in neurofibromatosis type 2 (NF2) and meningioma 1 (MN1) genes.

BACKGROUND: Meningiomas are tumors originating from the membranous layers surrounding the central nervous system, and are generally regarded as "benign" tumors of the brain. Malignant meningiomas are rare and are typically associated with a higher risk of local tumor recurrence and a poorer prognosis (median survival time <2 years). Previous genome-wide association studies and exome sequencing studies have identified genes that play a role in susceptibility to meningiomas, but these studies did not focus specifically on malignant tumors. METHODS: We performed exome sequencing on five malignant meningiomas on the Illumina HiSeq2000 platform using Agilent SureSelect Human All Exon kits. We used wANNOVAR web server to annotate and prioritize variants, identified candidate genes with recurrent mutations, and validated selected mutations by Sanger sequencing. We next designed custom NimbleGen targeted region arrays on five candidate genes, and sequenced four additional malignant meningiomas. RESULTS: From exome sequencing data, we identified several frequently mutated genes including NF2, MN1, ARID1B, SEMA4D, and MUC2, with private mutations in tumors. We sequenced these genes in four additional samples and identified potential driver mutations in NF2 (neurofibromatosis type 2) and MN1 (meningioma 1). CONCLUSIONS: We confirmed that mutations in NF2 may play a role in progression of meningiomas, and nominated MN1 as a candidate gene for malignant transformation of meningiomas. Our sample size is limited by the extreme rarity of malignant meningiomas, but our study represents one of the first sequencing studies focusing on the malignant subtype.

[Experimental study on radiofrequency ablation technology for treatment of infected wounds in minipigs].

OBJECTIVE: To observe the effect of radiofrequency ablation technology for the treatment of infected wounds in minipigs. METHODS: Infected wounds of full-thickness skin defects (about 6.15 cm2/wound) were prepared in 8 6-month-old minipigs (weighing, 30-35 kg) using the method of Davis et al. The 160 wounds were randomly divided into 4 groups (n = 40). Infected wounds were debrided with the radiofrequency ablation technology in group A, with the electric knife in group B, and with the scalpel in group C; no treatment was done in group D as a control. The healing rate, healing time, and tissue filling rate were observed; bacterial quantitative examination and histological examination were done at 0, 2, 7, and 14 days after operation. RESULTS: All infected wounds were successfully established after 48 hours when Staphylococcus aureus dilution were inoculated. The wounds after radiofrequency ablation technology treatment were fresh and flat with slight bleeding; the healing time of group A was significantly shorter than that of groups B, C, and D (P < 0.05), and the healing rate of group A was significantly higher than that of groups B, C, and D at 7 and 14 days after operation (P < 0.05). The tissue filling rate of group A was significantly higher than that of groups B, C, and D at 2 days after operation (P < 0.05); the tissue filling rates of groups A, B, and C were significantly higher than that of group D at 7 and 14 days after operation (P < 0.05). At 0, 2, 7, and 14 days, there were significant differences in the bacterial count per gram tissue among 4 groups (P < 0.05), the order from low to high was groups A, B, C, and D. The histological observation showed that the surface of wound was smooth in group A at 0 day, and group A was better than the other groups in wound healing; at 2 days, some exudates were observed in 4 groups, but it was least in group A. There was inflammatory cell infiltration in various degrees in 4 groups at 7 and 14 days; it was lightest in group A with thick epithelium and dense collagen bundles, followed by groups B and C, and it was severe in group D. CONCLUSION: The radiofrequency ablation technology can effectively remove the necrotic tissues of infected wounds, remarkably reduce the number of bacteria, improve the healing rate, and shorten the healing time of wounds.

Robust revascularization, despite impaired VEGF production, after meniscus allograft transplantation in rabbits.

BACKGROUND: Little is known about vascularization restoration and vascular circulation after allogenic graft transplantation, which are both important prerequisites for optimal use of allograft meniscus transplantation. PURPOSE: To study vascularization restoration through autograft and allograft meniscus models in Oryctolagus cuniculus. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-eight rabbits at mature bone age were randomized to receive either an autograft or allograft after the meniscus of the left knee was completely resected. Vascularization, blood circulation, histological characteristics of the grafted meniscus and surrounding tissues, and vascular endothelial growth factor (VEGF) expression in the meniscus were assessed at 4, 8, and 12 weeks after allograft or autologous transplantation. RESULTS: The grafted meniscus was in good condition and was well connected to the surrounding joint capsule, and no obvious damage of the joint cartilage at the tibial plateau was observed. Even though the revascularization pattern was similar in the 2 groups, the meniscus body showed vessel growth mainly at the adhesion margin for less than one-third of the meniscus transverse diameter, and no significant vascular distribution was found at the free margin. Blood circulation peaked after 8 weeks at the anterior and posterior horns and declined thereafter. This was mimicked by VEGF expression, which showed a progressive decrease with time, even though the vascular endothelial cells gradually increased over time. There were no statistical differences in the various assessments between the allograft and autograft groups. CONCLUSION: At 12 weeks after meniscus allografting, the vascular circulation had almost recovered and gradual reconstruction of cells and fibers had begun, mimicking similar observations in the autograft group. CLINICAL RELEVANCE: Our data provide test reference for clinical rehabilitation after meniscus autograft.

Arthroscopic combined medial and lateral meniscus transplantation after double-tunnel, double-bundle anterior cruciate ligament reconstruction in the same knee.

Meniscus transplantation in combination with anterior cruciate ligament (ACL) reconstruction has been used in the treatment of patients with meniscus and ACL deficiency. However, there have been no reports of arthroscopic surgery and the outcome of both medial and lateral meniscus allograft transplantation after double-tunnel, double-bundle ACL reconstruction. Herein, we report the case of a young male who received arthroscopic lateral and medial meniscectomy and ACL tibialis allograft reconstruction performed with the double-tunnel and double-bundle technique approximately 8 months after a knee injury. Approximately 4 months postoperatively he began to experience pain and weakness in the operated knee and subsequently underwent arthroscopic lateral and medial meniscus allograft transplantation in the same procedure. Second-look arthroscopy and magnetic resonance imaging revealed the meniscal allografts to have normal shape and the ACL grafts to be relatively intact at 18 and 30 months after surgery. His knee appeared stable and the range of motion was normal. Our hypothesis was that knee stability could reliably be restored with this combined procedure and the meniscal grafts and ACL graft could provide protection for each other. We suggest that medial and lateral meniscus allografts for one patient should be from the same donor. In the operation, attention must be paid to the direction of the bone tunnels used to fix the horns of the meniscal grafts to avoid communication with other tunnels in the tibial plateau.

[Clinical safety about repairing the peripheral nerve defects with chemically extracted acellular nerve allograft].

OBJECTIVE: To discuss the clinical safety about repairing the peripheral nerve defects with the acellular allogeneic nerve. METHODS: The 41 patients (male 38, female 3, age 10 - 55 years old, average 28.9 years old) who were performed chemically extracted acellular nerve allograft transplanting to repair nerve defects from 2002 to 2011. The average interval from injury to nerve repairing was 4.1 months (range, 10 hours to 9 months). There were 41 cases nerve defects including 10 brachial plexus nerves, 3 radial nerves of upper arm, 4 ulnar nerves of forearm, 12 digital and toe nerves, 2 sciatic nerves, 2 femoral nerves, 3 tibial nerves and 5 common peroneal nerves. There were 12 cases combined fractures and 20 soft tissue injury or defects. The average length of the nerve allograft to bridge the nerve defects was 6.1 cm (range, 2 - 10 cm). No immunosuppressive drugs were used in all cases. The clinical safety was evaluated through physical examination, blood biochemistry and immunity detection. RESULTS: All cases were followed up post-operation. They got primary wound healing except 2 superficial infection who got delay healing through dressings changing. No any adverse effects happened including immunological rejection, hypersensitivity reaction, deep infection, hepatotoxicity and nephrotoxicity. CONCLUSIONS: It is safe and feasible to repairing human peripheral nerve defects with chemically extracted acellular nerve allograft.