Comparing the efficacy and safety of high-voltage and standard-voltage pulsed radiofrequency for the treatment of postherpetic neuralgia: A pooled analysis from randomized controlled trials.

Postherpetic neuralgia (PHN) is one of the most common and serious complications of herpes zoster infection. Pulsed radiofrequency (PRF) therapy has emerged to be a neuromodulation technique for the treatment of PHN. Two therapeutic options are available for PRF, including high-voltage and standard-voltage PRF. Some studies suggested that the former one had better clinical efficacy than the latter one. For the first time, this pooled analysis compared the efficacy and safety of these two surgeries for the treatment of PHN. Five commonly used databases were applied to identify the eligible studies. This study was registered on the PROSPERO (ID: CRD42023460236), which provided more relevant information. Finally, four randomized controlled trials (RCTs) with 285 participants were included. The combined odds ratios (OR) showed that high-voltage PRF exhibited a significantly higher treatment efficiency than the standard PRF (OR = 1.4, 95%CI: 1.16 to 1.69, P < 0.001). Additionally, the visual analogue scale (VAS) in the high-voltage PRF group was significantly lower than that of the standard PRF group at one week (SMD = -0.776, 95%CI: -1.408 to -0.145, P = 0.016), one month (SMD = -0.544, 95%CI: -0.907 to -0.180, P = 0.003), and three months (SMD = -1.096, 95%CI: -1.504 to -0.687, P < 0.001) after treatment, particularly at the three months after surgery. However, the VAS was comparable between the two groups (SMD = -0.94, 95%CI: -1.985 to 0.104, P = 0.077). Patients who underwent high-voltage PRF did not have a significantly higher incidence of adverse events than those with standard PRF (OR = 1.56, 95%CI: 0.78 to 3.13, P = 0.208). In summary, the current study revealed that high-voltage PRF is superior to standard-voltage PRF in improving analgesic efficacy in patients with PHN. Additionally, it does not increase the incidence of treatment-related adverse effects. Further studies are still warranted to determine the optimal voltage and duration of PRF treatment for patients with PHN.

Knockdown of ZEB1 Inhibits Hypertrophic Scarring through Suppressing the Wnt/ß-catenin Signaling Pathway in a Mouse Model.

BACKGROUND: Hypertrophic scars (HS) cause functional impairment and cosmetic deformities following surgeries or burns (30% to 94%). There is no target therapy yet because the pathogenesis of HS progression is not well-known. In tissue fibrosis, Zinc finger E-box binding homeobox 1 (ZEB1) abnormal upregulation is an important cause for extracellular matrix (ECM) overexpression, which is the main molecular change in HS. Therefore, we hypothesized that ZEB1-knockdown inhibits HS formation. METHODS: ZEB1 expression in human HS and TGF-ß1-induced fibroblasts were identified by PCR and western blotting. ZEB1 was knockdown by siRNA in HS fibroblasts (HSFs) and mouse HS model (C57/BL6, male, 8-12 weeks). After 8-hour-transfection, HSFs were subjected to PCR, western blotting and CCK-8, apoptosis, migration and contraction assays. Mice HS were analyzed by HE staining, PCR and western blotting after 56 days. RESULTS: ZEB1 was upregulated in HS tissue (2.0-fold; p < 0.001). ZEB1 knockdown inhibited HSFs activity (0.6 to 0.7-fold; p < 0.001), the expression of fibrotic markers (0.4 to 0.6-fold; p < 0.001) and ß-catenin, cyclinD1 and c-Myc expression (0.5-fold; p < 0.001). In mouse HS models, HS skin thickness was thinner (1.60 ± 0.40 mm vs. 4.04 ± 0.36 mm; p < 0.001) after ZEB1 knockdown. CONCLUSIONS: Knockdown of ZEB1 inhibits HS formation both in vitro and in vivo. However, this is an in vitro/mouse model and more validation is needed. CLINICAL RELEVANCE STATEMENT: The discovery of ZEB1 as a mediator of HS formation might be a potential therapeutic target in HS treatment.

Internal iliac artery preservation during endovascular aortic repair using in situ laser fenestration.

OBJECTIVE: The purpose of the present study was to evaluate the technical and short-term clinical outcomes of internal iliac artery (IIA) reconstruction during endovascular aortic repair (EVAR) with in situ laser-assisted fenestration in cases of abdominal aortic aneurysm (AAA) in which the iliac artery is unfit for an internal branched device (IBD). METHODS: In the present single-institution retrospective study, we analyzed patients with AAAs who had undergone EVAR with in situ laser-assisted fenestration for IIA reconstruction between January 2018 and April 2021. The study included patients with iliac artery anatomy unfit for the use of commercial IBDs. The primary safety end point was freedom from major adverse events and unplanned reinterventions within 30 days. The primary efficacy end point was freedom from IIA restenosis, reintervention, and symptoms due to pelvic ischemia at 1 year after the procedure. RESULTS: A total of 20 patients requiring IIA reconstruction but with anatomy unfit for IBD placement were treated with in situ laser-assisted fenestration during EVAR for aortoiliac aneurysms during the study period. The mean age of our patients was 72 years, and 90% were men. The technical success rate was 100%. No patient had died within 30 days after the procedure. A suspicious IIA perforation had occurred in one patient, which was treated with an additional covered stent, for a primary safety end point of 95.0%. After a mean follow-up of 11 months, all except for one of the reconstructed IIAs were patent. Three patients reported symptoms of buttock claudication on the IIA occluded side at their 3-month follow-up after the procedure. However, these symptoms had subsided in two of these patients at 6 months. Type II endoleaks without sac expansion had occurred in two patients owing to retrograde blood flow from the inferior mesenteric artery and lumbar artery. Both patients were kept under close surveillance. The rate of freedom from major adverse events and unplanned reinterventions within 30 days (primary efficacy end point) was 86.3% at 1 year after procedure. CONCLUSIONS: In situ laser-assisted fenestration was found to be a safe and effective alternative method for IIA reconstruction during EVAR for aortoiliac aneurysms in patients with anatomy unfit for IBD.

Exosomes from Adipose Mesenchymal Stem Cells Overexpressing Stanniocalcin-1 Promote Reendothelialization After Carotid Endarterium Mechanical Injury.

OBJECTIVE: Stanniocalcin-1 (STC-1) is a secreted glycoprotein that participates in the regulation of inflammation, apoptosis, and necrosis. We investigated the reendothelialization effect of exosomes from adipose stem cells (ADSC) overexpressing STC-1 on injured carotid endarterium. METHODS: ADSCs were transfected with lentivirus vectors containing pre-STC-1. PHK-26 as molecular probe was used to track the exosomes engulfed by mice arterial endothelial cells (MAEC). The role of STC-1-ADSC-Exosome (S-ADSC-Exo) in MAECs was verified through scratch test and tube forming. Expressions of STC-1 and NLRP3 inflammasome were detected by western blot and quantitative reverse transcription polymerase chain reaction. Reendothelialization effect was inhibited by the antagonist of siRNA targeting STC-1. Carotid endarterium mechanical injury was induced by insertion with a guidewire into the common carotid artery lumen. Carotid arteries were harvested for histological examination, immunofluorescence staining, and Evan's blue staining. RESULTS: Transfection of STC-1 significantly enhanced STC-1 levels in ADSCs, their exosomes, and MAECs. Compared with the control group and the ADSC-Exo group, STC-1 enriched exosomes markedly inhibited the expressions of NLRP3, Caspase-1, and IL-1ß in MAECs, exhibited good lateral migration capacity, and promoted angiogenesis. Administration of siRNA targeting STC-1 completely abolished down-regulation of NLRP3, Caspase-1, and IL-1ß by STC-1 and inhibited effects of S-ADSC-Exo on lateral migration and angiogenesis. In vivo administration of S-ADSC-Exo had reendothelialization effect on post-injury carotid endarterium as evidenced by thinner arterial wall, low-expressed NLRP3 inflammasome, and more living endothelial cells. CONCLUSIONS: The reendothelialization effect of exosomes from ADSCs on post-injury carotid endarterium could be enhanced by genetic modification of the exosomes to contain elevated STC-1, possibly through suppression of NLRP3 inflammasome-mediated inflammation.

Efficacy and safety of treating chronic nonspecific low back pain with radial extracorporeal shock wave therapy (rESWT), rESWT combined with celecoxib and eperisone (C + E) or C + E alone: a prospective, randomized trial.

BACKGROUND: To investigate whether respectively radial extracoporeal shock wave therapy (rESWT) or a combination of rESWT, celecoxib and eperisone (rESWT + C + E) are superior in reducing pain in patients with chronic nonspecific low back pain (cnsLBP) compared to C + E alone (a standard treatment of this condition in China). METHODS: 140 patients with cnsLBP were randomly allocated to rESWT (n = 47), rESWT + C + E (n = 45) or C + E alone (n = 48) for four weeks between November 2017 and March 2019. Outcome was evaluated using the Pain Self-Efficacy Questionnaire (PSEQ), Numerical Rating Scale (NRS), Oswestry Low Back Pain Disability Questionnaire and Patient Health Questionnaire 9, collected at baseline as well as one week (W1), W2, W3, W4 and W12 after baseline. RESULTS: All scores showed a statistically significant improvement over time. The PSEQ and NRS scores showed a significant Time × Treatment effect. Patients treated with rESWT had significantly lower mean NRS values than patients treated with rESWT + C + E at W1 and W3, as well as than patients treated with C + E alone at W3 and W4. No severe adverse events were observed. CONCLUSIONS: rESWT may not be inferior to respectively rESWT + C + E or C + E alone in reducing pain in patients with cnsLBP. LEVEL OF EVIDENCE: Level I, prospective, randomized, active-controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03337607. Registered November 09, 2017, https://www.clinicaltrials.gov/ct2/show/NCT03337607 . LEVEL OF EVIDENCE: Level I; prospective, randomized, controlled trial.

Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia.

BACKGROUND: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. METHODS: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson's staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. RESULTS: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel's density than the ADSC-Exo and control groups by Masson's staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1ß, as well as the increased secretion of VEGF, IGF-1, and FGF. CONCLUSION: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

Outcomes of endovenous laser ablation with additional iliac vein stenting of nonthrombotic lesions in patients presenting with active venous ulcers.

OBJECTIVE: We evaluated the clinical outcomes of superficial and perforator ablation and the effects on wound healing by adding iliac vein stenting of nonthrombotic iliac vein lesions (NIVLs) in patients presenting with active venous ulcers. METHODS: A retrospective analysis was performed of patients who had presented with venous ulcers and had a diagnosis of NIVLs from January 2017 to December 2019. Patients with a >50% diameter reduction in the iliac vein as determined by computed tomography venography had undergone transfemoral venography for further confirmation. Patients were divided into the endovenous laser ablation (EVLA) group and EVLA with stenting (EVLAS) group. The EVLA group had undergone endovascular laser treatment of superficial venous reflux, and the EVLAS group had undergone EVLA and stenting for NIVLs. The clinical outcomes were compared between the two groups. The primary end point was cumulative ulcer healing at 12 months. The secondary end points included complications, venous clinical severity score improvements, and pain scores during the follow-up period. Univariable and multivariable regression models were used to determine the refractory ulcer predictors. RESULTS: A total of 157 patients were included, 93 in the EVLAS group and 64 in the EVLA group. Of the 93 patients in the EVLAS group and patients in the EVLA group, 30 (32.26%) and 17 (26.56%) had presented with iliac venous occlusion, respectively (P = .48). The mean percentage of stenosis was 78.0% ± 13.6% in EVLAS group and 77.0% ± 14.0% in the EVLA group (P = .36). No significant differences in the general preoperative data were observed between the two groups. Cumulative ulcer healing at 1 year was 86.8% and 65.6% in the EVLAS and EVLA groups, respectively (P = .001). After a mean follow-up of 22 months (median, 24 months), the EVLAS group had a significantly improved venous clinical severity score compared with the EVLA group (EVLAS group, 8.3; EVLA group, 11.7; P = .01). Multivariable analysis of the entire cohort showed that obesity and employment that requires standing were predictive of refractory ulcers and that iliac venous stent placement was a protective factor for ulcer healing. CONCLUSIONS: The results of the present study have suggested an association between improvement in the overall success of venous leg ulcer healing when including treatment of NIVLs with stents into a treatment plan that already includes saphenous and perforator vein ablation.

Comparing Safety and Efficacy of Rivaroxaban with Warfarin for Patients after Successful Stent Placement for Chronic Iliofemoral Occlusion: A Retrospective Single Institution Study.

OBJECTIVE: The aim was to compare the safety and effectiveness of rivaroxaban and warfarin as anticoagulants for treating patients with post-thrombotic syndrome (PTS) with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting. METHODS: This single institution retrospective study analysed patients with PTS with chronic iliofemoral venous occlusion who were prescribed rivaroxaban or warfarin for one year after successfully undergoing iliofemoral venous stenting. The primary safety and efficacy endpoints were bleeding complication rate and primary patency rate at one year. Secondary outcomes included Villalta score, symptom recurrence rate, ulcer healing rate, and clinically driven target lesion revascularisation (CD-TLR) rate during follow up. RESULTS: From January 2016 to December 2017, 154 legs from 154 patients were included in this study (69 in rivaroxaban group and 85 in warfarin group). The groups were well matched for patient demographics, clinical characteristics, and procedural details. There was no significant difference between the rivaroxaban group and warfarin group in bleeding complication rate (10% vs. 16%, p = .23, hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.25 - 1.37) at one year, as well as major bleeding complication rate (0% vs. 2%, p = .20, HR 0.16, 95% CI 0.01 - 2.61) and minor bleeding complication rate (10% vs. 14%, p = .40, HR 0.67, 95% CI 0.27 - 1.66). The primary patency rate was higher in the rivaroxaban group at one year (84% vs. 71%, p = .049, HR 0.50, 95% CI 0.26 - 0.96) and at two years (79% vs. 63%, p = .037, HR 0.52, 95% CI 0.29 - 0.93). At a mean follow up of 24 months (range 1 - 42 months), the rivaroxaban group had a significantly lower post-operative Villalta score (4.87 ± 3.51 vs. 6.88 ± 5.85, p = .010, t = 2.64, 95% CI 0.50 - 3.52), lower rate of symptom recurrence (4% vs. 32%, p < .001), lower CD-TLR rates (3% vs. 13%, p = .039), and higher ulcer healing rate (90% vs. 59%, p = .004) than the warfarin group. CONCLUSION: For PTS patients with chronic iliofemoral venous occlusion undergoing iliofemoral venous stenting, rivaroxaban probably exhibited similar safety but superior efficacy to warfarin. However, further prospective control studies with large sample size are necessary to confirm the results.

WeChat app-based reinforced education improves the quality of opioid titration treatment of cancer-related pain in outpatients: a randomized control study.

BACKGROUND: As inadequate pain communication contributes to difficulties in optimizing outcomes of outpatients, we investigated the effect of reinforced education using WeChat App to the opioid titration treatment of cancer-related pain in the outpatient setting. METHODS: We conducted a prospective study to compare reinforced education using Wechat with care as usual from February to December 2019. Patients in the reinforced education group received reinforced education via Wechat, while those in the control group received care as usual. Effect measurements for both groups are carried out with questionnaires at the baseline and 3 days later. Questionnaires include pain intensity (NRS), treatment-related adverse events, cancer-related quality of life (QOL), sleep (PSQI), satisfaction, anxiety (GAD-7) and depression (PHQ-9). Number of patients whose NRS reduced to less than three points in 24 h was the primary outcomes. Secondary outcomes included treatment-related adverse events, cancer-related quality of life, sleep, satisfaction, anxiety and depression. RESULTS: Although there was no significant difference regarding pain intensity (NRS) between the two groups at 72 h, the rate of NRS that reduced to less than three points in 24 h was significantly higher in the Wechat group than in the control group. Patients' satisfaction was significantly higher in the Wechat group than in the control group. There was no significant difference between the two groups regarding the other findings at 72 h, including pain intensity (NRS), cancer-related quality of life (QOL), anxiety (GAD-7), depression (PHQ-9), and sleep (PSQI). However, no significant difference was found between the two groups for constipation, nausea, vomiting, dizziness, somnolence, pruritus, loss of consciousness, and death. CONCLUSIONS: Our results indicated that receiving instructions delivered by Wechat resulted an increased number of patients with good pain control and better satisfaction. The study provided insight into the effectiveness of the reinforced education using a Wechat app delivered by a doctor to outpatients in the titration treatment of cancer-related pain. TRIAL REGISTRATION: This study was registered at chictr.org (Registration number: ChiCTR1900021150 , Date of Registration: January 30, 2019).

Allogeneic adipose-derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF-1α/IL-10 pathway.

Adipose-derived mesenchymal stem cells (ASCs) are multipotent stromal cells that possess considerable therapeutic potential for tissue remodeling. However, their protective mechanism in critical limb ischemia has not been fully defined. After the occlusion of blood vessels, hypoxia becomes a prominent feature of the ischemic limb. This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capacity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages toward the anti-inflammatory M2 phenotype. We further demonstrated that ASCs-derived interleukin 10 (IL-10), mediated by hypoxia inducible factor-1α (HIF-1α), played a crucial role in the induction of M2 macrophages by activating the signal transducer and activator of transcription 3 (STAT3)/Arginase (Arg-1) pathway. Our in vivo experiments revealed that transplanted ASCs exhibited an immunomodulatory effect by recruiting macrophages to ischemic muscle and increasing the density of M2 macrophages. The transplantation of ASCs into ischemic limbs induced increased blood flow reperfusion and limb salvage rate, whereas the depletion of tissue macrophages or transplanting HIF-1α-silenced ASCs inhibited the therapeutic effect. These findings elucidated the critical role of macrophages in ASCs-mediated ischemic muscle repair and proved that allogeneic ASCs could exert the protective effect by enhancing the recruitment of macrophages and inducing macrophages toward M2 phenotype through HIF-1α/IL-10 pathway.

A meta-analysis of combined proximal stent grafting with or without adjunctive distal bare stent for the management of aortic dissection.

BACKGROUND: The efficacy and safety of placement of a proximal covered stent graft combined with a distal bare stent are controversial because of the lack of evidence. This systematic review and meta-analysis compared the outcomes of combined proximal covered stent grafting with distal bare stenting (BS group) and proximal covered stent grafting without distal bare stenting (non-BS group). METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and key references were searched up to January 26, 2019. Predefined outcomes of interest were mortality, morbidity, and postoperative assessment of aortic remodeling. We pooled risk ratios (RRs) of the outcomes of interest using fixed effects model or random effects model. RESULTS: Overall, eight observational studies involving 914 patients were included. There were no significant differences in overall aorta-related mortality (RR, 0.54; confidence interval [CI], 0.24-1.24; P = .15), complete thoracic false lumen (FL) thrombosis rate (RR, 1.23; CI, 0.83-1.81; P = .30), or complete abdominal FL thrombosis rate (RR, 1.96; CI, 0.68-5.69; P = .21) between the BS group and the non-BS group. The BS group had a lower rate of partial thoracic FL thrombosis (RR, 0.40; CI, 0.25-0.65; P = .0002), a lower stent graft-induced new entry rate (RR, 0.08; CI, 0.02-0.41; P = .003), and a lower reintervention rate (RR, 0.42; CI, 0.26-0.69; P = .0005). CONCLUSIONS: Combined proximal covered stent grafting with distal adjunctive bare stenting had the potential to reduce the partial thoracic FL thrombosis rate and the rates of stent graft-induced new entry and reintervention but was not associated with lower aorta-related mortality or the complete FL thrombosis rate. Further research with a stricter methodology is needed.

Effects of ghrelin on pGSK-3ß and ß-catenin expression when protects against neuropathic pain behavior in rats challenged with chronic constriction injury.

Ghrelin has been shown to alleviate neuropathic pain by inhibiting the release of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK-3ß/ß-catenin signaling in mediating the effect of ghrelin on neuropathic pain and to understand the associated mechanisms. Chronic constriction injury (CCI) of the sciatic nerve was used to establish a rat model of neuropathic pain. Hyperalgesia and allodynia were evaluated by observing the mechanical withdrawal threshold and the thermal withdrawal latency. Wnt3a and ß-catenin protein expression and GSK-3ß phosphorylation were detected by western blotting analysis. The levels of tumor necrosis factor-α and IL-1ß were determined using an enzyme-linked immunosorbent assay. In addition, we used immunohistochemical analysis to determine the levels of GSK-3ß phosphorylation in the dorsal horn of the spinal cord. Intrathecal delivery of ghrelin effectively ameliorated CCI-induced mechanical allodynia and thermal hyperalgesia at 7 and 14 days and reduced the levels of tumor necrosis factor-α. Ghrelin inhibited CCI-induced GSK-3ß activation and ß-catenin overexpression in the spinal dorsal horn. Moreover, intrathecal injection of ghrelin suppressed the activation of GSK-3ß in the spinal dorsal horn of CCI rats, as assessed by immunohistochemical analysis. Our data indicated that ghrelin could markedly alleviate neuropathic pain by inhibiting the expression of ß-catenin, via the suppression of GSK-3ß activation, in the spinal cord of CCI rats.

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal ß-catenin in chronic constriction injury rats.

BACKGROUND AND OBJECTIVES: Pulsed radiofrequency (PRF) is a minimal neurodestructive interventional pain therapy. However, its analgesic mechanism remains largely unclear. We aimed to investigate the peripheral and spinal mechanisms of PRF applied either adjacent to the ipsilateral L5 dorsal root ganglion (PRF-DRG) or PRF to the sciatic nerve (PRF-SN) in the neuropathic pain behavior induced by chronic constriction injury (CCI) in rats. METHODS: On day 0, CCI or sham surgeries were performed. Rats then received either PRF-DRG, PRF-SN, or sham PRF treatment on day 4. Pain behavioral tests were conducted before surgeries and on days 1, 3, 5, 7, 9, 11, 13, and 14. After the behavioral tests, the rats were sacrificed. The venous blood or sciatic nerve samples were collected for ELISAs and the dorsal horns of the L4-L6 spinal cord were collected for western blot examination. RESULTS: The mechanical allodynia and the thermal hyperalgesia has been relieved by a single PRF-DRG or PRF-SN application. In addition, the analgesic effect of PRF-DRG was superior to PRF-SN on CCI-induced neuropathic pain. Either PRF-DRG or PRF-SN reversed the enhancement of interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels in the blood of CCI rats. PRF-DRG or PRF-SN also downregulated spinal ß-catenin expression. CONCLUSIONS: PRF treatment either to DRG or to sciatic nerve reduced neuropathic pain behavior, and reduced peripheral levels of pro-inflammatory cytokines and spinal ß-catenin expression in CCI rats. PRF to DRG has a better analgesic effect than PRF to the nerve.

Intrathecal morphine combined with ropivacaine induces spinal myoclonus in cancer patients with an implanted intrathecal drug delivery system: Three case reports.

RATIONALE: Although intrathecal opioid infusion has been used for decades for the treatment of severe pain, myoclonus as one of the complications of this therapeutic modality is now beginning to be recognized more. PATIENTS CONCERNS: Here, we report three patients who developed myoclonus after dose adjustment in intrathecal drug delivery system for the treatment of refractory cancer pain. DIAGNOSIS: Spinal myoclonus is a sudden, brief, shock-like muscle contractions originating from the central nervous system. In our cases, it occurred after opioid administration via intrathecal delivery system with no abnormality found in laboratory or imaging examinations. INTERVENTIONS: Spinal myoclonus can be treated effectively by reducing the dose or infusion rate as described in case 1, or changing from an intrathecal to systemic administration in case 2, or correcting infusion and bolus parameters mistakes in case 3. OUTCOMES: All patients recovered quickly after stopping or decreasing the intrathecal drug infusion. LESSONS: Prevention is more important than treatment as for spinal myoclonus. Pain management teams should be aware of this distressing complication. Dose of intrathecal drugs should not exceed the recommended maximal daily doses by guidelines and patient education is important for successful intrathecal analgesic therapy.

Patient-Controlled Intravenous Analgesia for Advanced Cancer Patients with Pain: A Retrospective Series Study.

Objective: To compare the efficacy and side effects of patient-controlled intravenous analgesia (PCIA) with hydromorphone, sufentanil, and oxycodone on the management of advanced cancer patients with pain. Methods: Patients allocated to receive PCIA between January 2015 and December 2016 were chosen for this study. After reviewing medical records, we verified if hydromorphone, sufentanil, or oxycodone for PCIA could equally provide effective pain relief. A numeric rating scale (NRS) of cancer pain was applied before PCIA, at 4 hours after PCIA, and at the discontinuation of PCIA. Secondary, the incidence of clinical side effects attributed to PCIA was observed. Results: A total of 85 medical records were reviewed. PCIA with hydromorphone (n=30), sufentanil (n=34), and oxycodone (n=21) was used for cancer pain management. PCIA successfully improved pain control in 97.6% of the patients. The most common side effects were constipation (11.8%), nausea (8.2%), and sedation (5.9%). Drug addiction, delirium, or respiratory depression associated with PCIA was not reported in this case series study. No significant intergroup difference was observed in NRS at any of the abovementioned time points. There was no significant difference of analgesic effect among the hydromorphone, sufentanil, or oxycodone. Conclusion: PCIA provided timely, safe, and satisfactory analgesia for advanced cancer patients with pain and may be useful for titration of opioids, management of severe breakthrough pain, and conversion to oral analgesia. There was no significant difference of analgesic effect and side effect among the hydromorphone, sufentanil, and oxycodone.

Prospective investigation of intravenous patient-controlled analgesia with hydromorphone or sufentanil: impact on mood, opioid adverse effects, and recovery.

BACKGROUND: Radical surgery for colorectal cancer, associated with moderate to severe postoperative pain, needs multimodal analgesia with opioid for analgesia. Despite considerable advancements, the psychological implications and other side effects with opioid remain substantially unresolved. This study aimed to investigate the impact on mood, side effects relative to opioid, and recovery of the patients with hydromorphone or sufentanil intravenous patient-controlled analgesia (IV-PCA) in a multimodal perioperative analgesia regimen undergoing radical surgery for colorectal cancer. METHODS: Eighty patients undergoing elective laparoscopic or open radical surgery for colorectal cancer under general anesthesia were randomized to receive postoperative IV-PCA with either sufentanil (group S) or hydromorphone (group H). All patients received additionally flurbiprofen axetil 50 mg 30 min before the end of surgery and wound infiltration with 10 ml of 0.75% ropivacaine at the end of surgery. The primary endpoint was mood changes at 48 and 96 h after surgery. The secondary endpoints were the incidence of opioid-related adverse effects, recovery results and patient satisfaction after surgery. RESULTS: Seventy-two patients completed the study finally. There were no significant differences between the two groups with respect to preoperative parameters, surgical and anesthetic characteristics (P > 0.05). No obvious significant differences were observed in VAS score (at rest and during mobilization) and rescue analgesics use (P > 0.05). Compared with group S, the anger scores in the group H at 48 h and 96 h after surgery were significantly lower (P = 0.012 and 0.005; respectively), but the incidences of pruritus and nausea were higher (P = 0.028 and 0.008; respectively). There were no significant differences in the incidences of vomiting, respiratory depression, dizziness, Ramsay score, and hemodynamic changes between the two groups (P > 0.05). Moreover, there were no significant differences in the time to gastrointestinal recovery, time to drainage tube removal, time to walk, hospital stay after surgery and patient satisfaction between the two groups (P > 0.05). CONCLUSIONS: Under the similar analgesia effect with different opoiods postoperatively, hydromorphone IV-PCA resulted in an improved mood, however, a higher occurrence of pruritus and nausea while compared to sufentanil IV-PCA in a multimodal perioperative analgesia regimen. Both regimens of opioid with IV-PCA may serve as promising candidates for good postoperative pain management, and provide with similar postoperative recovery for the patients undergoing radical surgery for colorectal cancer. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry on September 20, 2015 (URL: http://www.chictr.org.cn . Registry number: ChiCTR-IPR-15007112).

Functional blocking of Ninjurin1 as a strategy for protecting endothelial cells in diabetes mellitus.

Ongoing efforts to remove pathological inflammatory stimuli are crucial for the protection of endothelial cells in diabetes. Nerve injury-induced protein 1 (Ninj1) is an adhesion molecule that not only contributes to inflammation but also regulates the apoptosis of endothelial cells. In the present study, Ninj1 was found highly expressed in endothelial cells in Type 2 diabetic mice and increased in high-glucose (HG) cultured HUVECs. Furthermore, we found that Ninj1 levels are up-regulated in endothelial cells in clinical specimens of diabetic patients when compared with nondiabetic tissues, indicating a biological correlation between Ninj1 and endothelial pathophysiology in diabetic condition. Functional blocking of Ninj1 promoted endothelial tube formation and eNOS phosphorylation in the HG condition. Additionally, blocking Ninj1 inhibited the activation of caspase-3 and increased the Bcl-2/Bax ratio, thus inhibiting HUVECs apoptosis induced by HG. HG-induced ROS overproduction, p38 MAPK and NF-κB activation, and the overexpression of VCAM-1, ICAM-1, MCP-1, and IL-6 genes were ameliorated after Ninj1 was blocked. Using the signaling pathway inhibitor LY294002, we found that Bcl-2 expression and eNOS phosphorylation after Ninj1 blockade were regulated via PI3K/Akt signaling pathway. The in vivo endothelial contents, α-SMA+PECAM-1+ vascular numbers, and blood perfusion in the hindlimb were markedly up-regulated after Ninj1 was blocked. According to our findings, functional blocking of Ninj1 shows protective effects on diabetic endothelial cells both in vitro and in vivo Thus, we consider Ninj1 to be a potential therapeutic target for preventing endothelial dysfunction in diabetes mellitus.

Inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization: an in vivo study.

OBJECTIVE: The purpose of this study is to explore the inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization (CNV) in rabbit models. METHODS: Sixty-five rabbits were used to establish alkali-induced CNV models. After the operation, rabbits were given daily antibiotic eye drops and an eye ointment to prevent infection. The models were assigned to either an S100A4 siRNA or an empty vector group. Thirty rabbits were selected as the normal control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression of S100A4, vascular endothelial growth factor (VEGF), and tumor necrosis factor-α (TNF-α) in corneal tissues. Immunohistochemistry was used to detect the protein expression of VEGF in corneal tissues, and an enzyme-linked immunosorbent (ELISA) assay was used to detect the protein expression of VEGF and TNF-α in the aqueous humor. RESULTS: The qRT-PCR results showed that S100A4 mRNA expression was lower in the S100A4 siRNA group than in the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. When compared with the empty vector group, the expression of VEGF and TNF-α mRNA was downregulated in the S100A4 siRNA group. The immunohistochemistry results revealed that VEGF protein expression was downregulated in the S100A4 siRNA group when compared to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. The ELISA results suggest that VEGF and TNF-α protein expression is downregulated in the S100A4 siRNA group in comparison to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. CONCLUSIONS: These findings indicate that S100A4 gene silencing can inhibit alkali burn-induced CNV in rabbits.

In Situ Laser Fenestration Is a Feasible Method for Revascularization of Aortic Arch During Thoracic Endovascular Aortic Repair.

BACKGROUND: Reconstruction of the aortic major branches during thoracic endovascular aortic repair is complicated because of the complex anatomic configuration and variation of the aortic arch. In situ laser fenestration has shown great potential for the revascularization of aortic branches. This study aims to evaluate the feasibility, effectiveness, and safety of in situ laser fenestration on the three branches of the aortic arch during thoracic endovascular aortic repair. METHODS AND RESULTS: Before clinical application, the polytetrafluoroethylene and Dacron grafts were fenestrated by an 810-nm laser system ex vivo, which did not damage the bare metal portion of the endografts and created a clean fenestration while maintaining the integrity of the endografts. In vivo, 6 anesthetized female swine survived after this operation, including stent-graft implantation in the aortic arches, laser fenestration, and conduit implantation through the innominate arteries and the left carotid arteries. Based on the animal experiments, in situ laser fenestration during thoracic endovascular aortic repair was successively performed on 24 patients (aged 33-86 years) with aortic artery diseases (dissection type A: n=4, type B: n=7, aneurysm: n=2, mural thrombus: n=7). Fenestration of 3 aortic branches was performed in 2 (8.3%) patients. Both the left carotid artery and the left subclavian artery were fenestrated in 6 (25%) patients. Only left subclavian artery fenestration surgery was done in 16 (66.7%) patients. Among these patients, 1 fenestration was abandoned secondary to an acute takeoff of the innominate artery in a type III aortic arch. The average operative time was 137±15 minutes. The technical success rate was 95.8% (n=23). No fenestration-related complications or neurological morbidity occurred after this operation. During a mean postoperative 10-month follow-up (range: 2-17 months), 1 patient died of severe pneumonia, and all the left subclavian artery and carotid artery stents were patent with no fenestration-related endoleaks upon computed tomography angiography images. CONCLUSIONS: In situ laser fenestration is a feasible, effective, rapid, repeatable, and safe option for the reconstruction of aortic arch during thoracic endovascular aortic repair, which might be available to revascularize the 3 branches. However, follow-up periods should be extended to evaluate the robustness of this technique.

Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia.

Adipose-derived stem cell (ADSC)-based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs (D-ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objective of the present study was to detect whether overexpression of methylglyoxal-metabolizing enzyme glyoxalase-1 (GLO1), which reduces ROS in D-ADSCs, can restore their proangiogenic function in a streptozotocin-induced diabetic mice model of CLI. GLO1 overexpression in D-ADSCs (G-D-ADSCs) was achieved using the lentivirus method. G-D-ADSCs showed a significant decrease in intracellular ROS accumulation, increase in cell viability, and resistance to apoptosis under high-glucose conditions compared with D-ADSCs. G-D-ADSCs also performed better in terms of migration, differentiation, and proangiogenic capacity than D-ADSCs in a high-glucose environment. Notably, these properties were restored to the same level as that of nondiabetic ADSCs under high-glucose conditions. G-D-ADSC transplantation induced improved reperfusion and an increased limb salvage rate compared D-ADSCs in a diabetic mice model of CLI. Histological analysis revealed higher microvessel densities and more G-D-ADSC-incorporated microvessels in the G-D-ADSC group than in the D-ADSC group, which was comparable to the nondiabetic ADSC group. Higher expression of vascular endothelial growth factor A and stromal cell-derived factor-1α and lower expression of hypoxia-induced factor-1α were also detected in the ischemic muscles from the G-D-ADSC group than that of the D-ADSC group. The results of the present study have demonstrated that protection from ROS accumulation by GLO1 overexpression is effective in reversing the impaired biological function of D-ADSCs in promoting neovascularization of diabetic CLI mice model and warrants the future clinical application of D-ADSC-based therapy in diabetic patients. Stem Cells Translational Medicine 2017;6:261-271.