A Circulating Panel of circRNA Biomarkers for the Noninvasive and Early Detection of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.

The role of proteomics in acute pancreatitis: new and old knowledge.

INTRODUCTION: Around 20% of individuals diagnosed with acute pancreatitis (AP) may develop severe acute pancreatitis (SAP), possibly resulting in a mortality rate ranging from 15% to 35%. There is an urgent need to thoroughly understand the molecular phenotypes of SAP resulting from diverse etiologies. The field of translational research on AP has seen the use of several innovative proteomic methodologies via the ongoing improvement of isolation, tagging, and quantification methods. AREAS COVERED: This paper provides a comprehensive overview of differentially abundant proteins (DAPs) identified in AP by searching the PubMed/MEDLINE database (2003-2023) and adds significantly to the current theoretical framework. EXPERT OPINION: DAPs for potentially diagnosing AP based on proteomic identification need to be confirmed by multi-center studies that include larger samples. The discovery of DAPs in various organs at different AP stages via proteomic technologies is essential better to understand the pathophysiology of AP-related multiple organ dysfunction syndrome. Regarding the translational research of AP, novel approaches like single-cell proteomics and imaging using mass spectrometry may be used as soon as they become available.

Cardiac complications caused by biliary diseases: A review of clinical manifestations, pathogenesis and treatment strategies of cholecardia syndrome.

Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.

Polymer Dielectrics with Outstanding Dielectric Characteristics via Passivation with Oxygen Atoms through C-F Vacancy Carbonylation.

The development of advanced electrical equipment necessitates polymer dielectrics with a higher electric strength. Unfortunately, this bottleneck problem has yet to be solved because current material modification methods do not allow direct control of deep traps. Here, we propose a method for directly passivating deep traps. Measurements of nanoscale microregion charge characteristics and trap parameters reveal a significant reduction in the number of deep traps. The resulting polymer dielectric has an impressively high electrical strength, less surface charge accumulation, and a significantly increased flashover voltage and breakdown strength. In addition, the energy storage density is increased without sacrificing the charge-discharge efficiency. This reveals a new approach to increasing the energy storage density by reducing the trap energy levels at the electrode-dielectric interface. We further calculated and analyzed the microscopic physical mechanism of deep trap passivation based on density functional theory and characterized the contributions of orbital composition and orbital hybridization.

Outcomes of allogeneic or autologous stem cell transplantation followed by maintenance chemotherapy in adult patient with B-ALL in CR1 with no detectable minimal residual disease.

Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.

Eliminating COVID-19 as the immediate culprit for igniting pancreatitis.

The impact of severe acute respiratory syndrome coronavirus 2 infection on the potential development of pancreatitis is a subject of ongoing debate within academic discourse. Establishing a causal link between COVID-19 and pancreatitis may not be fully supported by relying only on retrospective studies or case reports. This study examined the relationship between COVID-19 phenotypes and pancreatitis by Mendelian randomization (MR) method. The identification of instrumental variables (single nucleotide polymorphisms) that exhibit a robust association with the COVID-19 phenotypes was accomplished through a meticulous process of rigorous screening procedures. We included acute pancreatitis and chronic pancreatitis (CP) as the outcomes in the MR analysis, even though no definitive studies exist between COVID-19 and CP. A direct causal relationship between genetically predicted COVID-19 phenotypes and pancreatitis risk cannot be established. There is an ongoing debate over the designation of COVID-19 as a definitive cause of pancreatitis.

Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention.

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.

Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).

Lignin Degradation via Chlorine Dioxide at Room Temperature: Chemical Groups and Structural Characterization.

Lignin degradation is an effective means of achieving the high-value application of lignin, but degradation usually requires the use of high temperatures and harsh reaction-conditions. This study describes a green, mild approach for the degradation of lignin, in which chlorine dioxide (ClO2) was used for the oxidative degradation of lignin (IL) in an acidic aqueous suspension at room temperature. The optimal process conditions were: 30 mL of ClO2 solution (2.5 mg·L-1), pH 4.5 and 3 h. The FT-IR, NMR (1H NMR, 2D-HSQC and 31P NMR), XPS and GPC analyses indicated that lignin could be degraded by ClO2 relatively well at room temperature, to form quinones and muconic acids. Additionally, DIL was reduced to substances with a high phenolic-hydroxyl (OH) content (RDIL) under the presence of NaBH4, which further confirmed the composition of DIL and which can be applied to the development of lignin-based phenolic resins, providing a reference for the further modification as well as the utilization of DIL.

Retractions relevant to COVID-19: does the retraction rate jump during the pandemic?

INTRODUCTION: Since the outbreak of Coronavirus Disease 2019, the scientific community has acted promptly before many publications appeared in the scientific literature. It posed a question of whether the expedited research and publication process would impair the research integrity, further leading to the rise in retractions. Hence in this study, we aimed to examine the characteristics of retracted articles related to COVID-19 and provide some insight into the scientific publishing of COVID-19 literature. METHODS: In this study, by searching Retraction Watch on 10 March 2022, the largest database on retraction, we included 218 COVID-19-related retracted articles. RESULTS: We found that the retraction rate of COVID-19 research was 0.04%. Of the 218 papers, 32.6% were retracted or withdrawn with a retraction notice giving no indication of the reason, and 9.2% due to honest mistakes made by authors. Retractions owing to misbehavior by authors comprised 33% of those retractions. DISCUSSION: We came to the conclusion that the changed publication norms certainly led to a number of retractions that could have been circumvented, the post-publication review and scrutiny were also enhanced.

Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We presented a case with NETs G1 of the hilar bile duct and the challenges for her treatment. CASE PRESENTATION: A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was Bismuth type II hilar cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathological and immunohistochemical examination indicated a perihilar bile duct NETs G1 with the microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 24 months without recurrence or disease progression. CONCLUSION: We know little of biliary NETs because of its rarity. There are currently no guidelines for the diagnosis and treatment of biliary NETs. We reported a case of perihilar bile duct NETs G1 with R1 resection, as far as we know this is the first report. More information about biliary NETs should be registered.

Effect of emodin on long non-coding RNA-mRNA networks in rats with severe acute pancreatitis-induced acute lung injury.

Long non-coding RNAs (lncRNAs) contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for treating severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin-treated and control rats were higher than DEX-treated and -untreated animals. By comparison of control and SAP-ALI animals, more up-regulated than down-regulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more down-regulated than up-regulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both up-regulated mRNA and co-expressed genes with up-regulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin-associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin- and DEX-treated rats. Also, emodin had different effects compared with DEX on co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treating SAP-ALI.

The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies.

Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfunctions caused by OJ-induced kidney injury as OJKI. However, the etiology of OJKI is still not fully clear, and research studies on how OJKI becomes a facilitated factor of OJ are limited. This article reviews the underlying pathological mechanism from five aspects, including metabolisms of bile acids, hemodynamic disturbances, oxidative stress, inflammation and the organic transporter system. Some nephrotoxic drugs and measures that can enhance or reduce the renal function with potential intervention in perioperative periods to alleviate the incidence of OJKI were also described. Furthermore, a more in-depth study on the pathogenesis of OJKI from multiple aspects for exploring more targeted treatment measures were further put forward, which may provide new methods for the prevention and treatment of clinical OJKI and improve the prognosis.

DCs-based therapies: potential strategies in severe SARS-CoV-2 infection.

Pneumonia caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is spreading globally. There have been strenuous efforts to reveal the mechanisms that the host defends itself against invasion by this virus. The immune system could play a crucial role in virus infection. Dendritic cell as sentinel of the immune system plays an irreplaceable role. Dendritic cells-based therapeutic approach may be a potential strategy for SARS-CoV-2 infection. In this review, the characteristics of coronavirus are described briefly. We focus on the essential functions of dendritic cell in severe SARS-CoV-2 infection. Basis of treatment based dendritic cells to combat coronavirus infections is summarized. Finally, we propose that the combination of DCs based vaccine and other therapy is worth further study.

Metal nanoparticle-doped epoxy resin to suppress surface charge accumulation on insulators under DC voltage.

In high-voltage direct current (HVDC) transmission systems, electric charge accumulates on insulator surfaces, causing surface electric field distortion and flashover voltage reduction. Therefore, studying a material that can improve the insulator surface insulation strength is of great engineering value. In this work, several types of metal nanoparticles with different particle sizes and concentrations are doped into epoxy resin. The experimental phenomena enables some interesting conclusions: when no agglomeration of doped nanoparticles occurs, a higher doping concentration provides a better insulation performance. The larger the doping particle size is, the lower the insulation performance. Additionally, under the same conditions, different types of metal nanoparticles lead to slightly different results after doping. Especially after doping with low concentration (approximately 120 parts per million (ppm)) and small particle size (approximately 10 nm) nanocopper particles, the insulator surface charge accumulation was effectively suppressed, and the flashover voltage was significantly improved. Our analysis suggests that it may be related to the single-electron tunneling phenomenon. Relevant results provide a new way to improve the surface insulation strength of insulators in the future.

A single-electron tunneling model: a theoretical analysis of a metal nanoparticle-doped epoxy resin to suppress surface charge accumulation on insulators subjected to DC voltages.

In high-voltage direct current transmission systems, charges accumulate at the gas-solid interface, distorting the local field strength, causing a reduction in the flashover voltage, and threatening the safe and reliable operation of the power system. The latest research has found that doping metal nanoparticles into an epoxy resin effectively suppresses the surface charge accumulation on insulators and improves their flashover voltage. This paper further analyzes the microscopic mechanism of this phenomenon, establishes a single-electron tunneling mode, and draws two conclusions: when there is no agglomeration of the doped nanoparticles, a higher doping concentration can be achieved, which provides a better insulative performance. The optimal metal nanoparticle radius is several to tens of nanometers. This work provides theoretical guidance for the future improvement of insulating materials through metal nanoparticle doping and has good prospects in engineering applications.

Lactobacillus rhamnosus GG microcapsules inhibit Escherichia coli biofilm formation in coculture.

OBJECTIVES: Microbial biofilms have become one of the most significant causes of nosocomial infections. The aim of this study was to examine the potential quorum sensing inhibitor activities of Lactobacillus rhamnosus GG microcapsules. RESULTS: Lactobacillus rhamnosus GG microcapsules effectively inhibited initial biofilm formation at a concentration of 2.5 × 108 CFU/mL. Furthermore, the inhibition rate was increased to 79% in the Lactobacillus rhamnosus GG microcapsules group, resulting in a reduction in the biofilm maturation stage. In addition, real-time PCR analysis revealed that the LGG microcapsules can act as effective inhibitors of transcriptional activators of the quorum sensing circuit in E.coli, luxS, lsrK, and lsrR. CONCLUSIONS: Lactobacillus rhamnosus GG microcapsules can effectively inhibit biofilm formation and disturb mature biofilms.

Therapeutic effect of a temporary transpyloric stent in refractory post-surgical gastroparesis: a case report.

BACKGROUND: Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. It was reported that the symptoms of diabetic gastroparesis had been greatly improved by transpyloric stent placement. However, the use of stents in benign conditions is considered to be contraindicated because of the increasing risk of complications, such as stent migration, reflux, perforation, bleeding, and, most importantly, new strictures caused by stent-induced tissue hyperplasia. While temporary placement of a self-expanding metallic stent (SEMC) can drastically reduce the risk of complications, few reports are available on the treatment of refractory PSG by temporary transpyloric stent. Does it have a long-term clinical effect after the stent being retrieved? CASE PRESENTATION: After accepting partial resection of the lesser curvature in another hospital, a patient developed refractory gastroparesis. The symptoms hadn't been improved after long-term drug therapy and balloon dilation therapy. Four months after surgery, a fully covered SEMC was placed by endoscopy in our hospital. Gastroparesis had been greatly improved. Two weeks later, the transpyloric stent was retrieved and the patient didn't show recurrent symptoms. Follow-ups were arranged at 3 months, 6 months and 1 year respectively, and there was no evidence of recurrence was found. CONCLUSIONS: This case indicates that temporary transpyloric SEMC is a safe, effective and less invasive alternative for post-surgical gastroparesis patients.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia.

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

The role of RhoA in retrograde neuronal death and axon regeneration after spinal cord injury.

Paralysis following spinal cord injury (SCI) is due to interruption of axons and their failure to regenerate. It has been suggested that the small GTPase RhoA may be an intracellular signaling convergence point for several types of growth-inhibiting extracellular molecules. Even if this is true in vitro, it is not clear from studies in mammalian SCI, whether the effects of RhoA manipulations on axon growth in vivo are due to a RhoA-mediated inhibition of true regeneration or only of collateral sprouting from spared axons, since work on SCI generally is performed with partial injury models. RhoA also has been implicated in local neuronal apoptosis after SCI, but whether this reflects an effect on axotomy-induced cell death or an effect on other pathological mechanisms is not known. In order to resolve these ambiguities, we studied the effects of RhoA knockdown in the sea lamprey central nervous system (CNS), where after complete spinal cord transection (TX), robust but incomplete regeneration of large axons belonging to individually identified reticulospinal (RS) neurons occurs, and where some RS neurons show unambiguous delayed retrograde apoptosis after axotomy. RhoA protein was detected in neurons and axons of the lamprey brain and spinal cord, and its expression was increased post-TX. Knockdown of RhoA in vivo by retrogradely-delivered morpholino antisense oligonucleotides (MOs) to the RS neurons significantly reduced retrograde apoptosis signaling in identified RS neurons post-SCI, as indicated by Fluorochrome Labeled Inhibitor of Caspases (FLICA) in brain wholemounts. In individual RS neurons, the reduction of caspase activation by RhoA knockdown began at 2weeks post-TX and was still seen at 8weeks. RhoA knockdown slowed axon retraction and possibly increased early axon regeneration in the proximal stump. The number of axons regenerating beyond the lesion more than 5mm at 10weeks post-TX also was increased. Thus RhoA knockdown both enhanced true axon regeneration and inhibited retrograde apoptosis signaling after SCI.