Radiographic and clinical outcomes of robot-assisted pedicle screw instrumentation for adolescent idiopathic scoliosis.

Introduction: Pedicle screw instrumentation (PSI) serves as the widely accepted surgical treatment for adolescent idiopathic scoliosis (AIS). The accuracy of screw positioning has remarkably improved with robotic assistance. Nonetheless, its impact on radiographic and clinical outcomes remains unexplored. This study aimed to investigate the radiographic and clinical outcomes of robot-assisted PSI vs. conventional freehand method in AIS patients. Methods: Data of AIS patients who underwent PSI with all pedicle screws between April 2013 and March 2022 were included and retrospectively analyzed; those with hybrid implants were excluded. Recruited individuals were divided into the Robot-assisted or Freehand group according to the technique used. Radiographic parameters and clinical outcome measures were documented. Results: In total, 50 patients (19, Freehand group; 31, Robot-assisted group) were eligible, with an average age and follow-up period of 17.6 years and 60.2 months, respectively, and female predominance (40/50, 80.0%). The correction rates of Cobb's angles for both groups were significant postoperatively. Compared to freehand, the robot-assisted technique achieved a significantly reduced breech rate and provided better trunk shift and radiographic shoulder height correction with preserved lumbar lordosis, resulting in significantly improved visual analog scale scores for back pain from the third postoperative month. Conclusion: Overall, robot-assisted PSI provides satisfactory radiographic and clinical outcomes in AIS patients.

Ultrasound imaging for preoperative assessment of extensor tendon tear following distal radius fracture.

Open reduction with internal fixation is a common approach for treating distal radius fractures. However, complications such as extensor tendon rupture can occur following this procedure. In this case report, we present a patient who experienced extensor tendon rupture following volar plate fixation of a distal radius fracture. The rupture was diagnosed preoperatively using ultrasound. We highlight the potential usefulness of ultrasound as a convenient and sensitive tool for diagnosing tendon injuries in patients with suspected complications following internal fixation of distal radius fractures. Furthermore, we discuss how ultrasound images can aid in localizing the site of tendon rupture and guide surgical incisions for smaller postoperative wound care, resulting in improved cosmetic outcomes.

Guanylate binding protein 5 triggers NF-κB activation to foster radioresistance, metastatic progression and PD-L1 expression in oral squamous cell carcinoma.

Radioresistance and metastasis are critical issues in managing oral squamous cell carcinoma (OSCC). Although immune checkpoint inhibitors (ICIs) has been recommended to treat OSCC, lacking useful biomarkers limited their anti-cancer effectiveness. We found that guanylate binding protein 5 (GBP5) is upregulated in primary tumors and associates with radioresistance in OSCC. GBP5 expression causally associated with cellular radioresistance and migration ability in the OSCC cell variants. GBP5 upregulation was examined to be correlated with NF-κB activation and programmed cell death-ligand 1 (PD-L1) elevation in OSCC samples. GBP5 knockdown was mitigated, but overexpression enhanced, NF-κB activity and PD-L1 expression in the OSCC cells. NF-κB inhibition by SN50 dramatically suppressed the GBP5-forested irradiation resistance, cellular migration ability and PD-L1 expression in OSCC cells. Importantly, GBP5 upregulation predicted a favorable outcome in cancer patients received ICI treatment. Our findings provide GBP5 as a useful biomarker to predict the anti-OSCC effectiveness of irradiation and ICIs.

Efficacy of local infiltration of tranexamic acid in subcutaneous surgery: A protocol from a single medical center.

BACKGROUND: The purpose of this study was to explore efficacy of locally injected tranexamic acid (TXA) at a concentration of 1 mg/mL for reduction perioperative bleeding and postoperative complications in subcutaneous tumor excisions. We present the protocol and also compare results between the group of use antithrombotic group and not used. METHODS: This is a retrospective study. Fifty-three patients were divided into 3 groups. Group 1 (n = 14): using antithrombotic drugs (antiplatelet or anticoagulants) with locally injected TXA. Group 2 (n = 17): using antithrombotic drugs without locally injected TXA. Group 3 (n = 22): not using antithrombotic drugs but with locally injected TXA. TXA was diluted to 1 mg/mL for use based on our experience. All patients were operated by 1 surgeon in 1 single medical center in Taipei from March 1st, 2020, to March 31st 2022. Outcomes such as the quality of perioperative surgical field and postoperative surgical complications were evaluated and compared. The quality of field was intraoperatively recorded by an assessment and photos from the surgeon. The statistical relationships between the complication rates were analyzed using χ2 test and a 1-way ANOVA by SPSS 25. RESULTS: From Groups 1 and 3, a total of 36 patients, 29 patients had a clear surgical field during procedure. When comparing Groups 1 and 2, use of locally injected TXA had greater positive advantage in terms of a clearer vision whilst surgery (P = .031). Group 2 had more minor complications such as hematoma, severe ecchymosis, wound dehiscence, wound infection. By postoperatively reducing hematomas for 24 hours, it significantly reduce the incidence of abovementioned minor complications (P = .036). With the help of locally injected TXA, shorter time was required to remove drain, hence reducing duration of in-hospital stay. CONCLUSION: The use of locally injected TXA whilst performing subcutaneous surgery on patients taking antithrombotic drugs is cost-effective. It could reduce bleeding and provide a more effective surgical field. In our study, favorable results were obtained from the use of diluted tranexamic acid (1 mg/mL) mixed with lidocaine, namely in clearing the surgical field as well as reducing postoperative surgical complications.

A salivary GMC oxidoreductase of Manduca sexta re-arranges the green leaf volatile profile of its host plant.

Green leaf volatiles (GLVs) are short-chain oxylipins that are emitted from plants in response to stress. Previous studies have shown that oral secretions (OS) of the tobacco hornworm Manduca sexta, introduced into plant wounds during feeding, catalyze the re-arrangement of GLVs from Z-3- to E-2-isomers. This change in the volatile signal however is bittersweet for the insect as it can be used by their natural enemies, as a prey location cue. Here we show that (3Z):(2E)-hexenal isomerase (Hi-1) in M. sexta's OS catalyzes the conversion of the GLV Z-3-hexenal to E-2-hexenal. Hi-1 mutants that were raised on a GLV-free diet showed developmental disorders, indicating that Hi-1 also metabolizes other substrates important for the insect's development. Phylogenetic analysis placed Hi-1 within the GMCß-subfamily and showed that Hi-1 homologs from other lepidopterans could catalyze similar reactions. Our results indicate that Hi-1 not only modulates the plant's GLV-bouquet but also functions in insect development.

Comparison of LeniScar Silicone Stick (AnsCare) With Traditional Silicone Gel (Dermatix Ultra) in Wound Scar Prevention and Removal.

BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.

Correlation of Foraminal Parameters with Patient-Reported Outcomes in Patient with Degenerative Lumbar Foraminal Stenosis.

The relationship between quantitative anatomic parameters in MRI and patient-reported outcomes (PROs) before and after surgery in degenerative lumbar foraminal stenosis remains unknown. We included 58 patients who underwent transforaminal lumbar interbody fusion (TLIF) for single-level degenerative disc disease with foraminal stenosis between February 2013 and June 2020. PROs were evaluated using the visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). The foraminal parameters assessed using preoperative MRI included foraminal height, posterior intervertebral disc height, superior and inferior foraminal width, and foraminal area. The correlation between foraminal parameters and PROs before operation, at 1 year follow-up, and change from baseline were assessed. The associations between the aforementioned parameters were examined using linear regression analysis. The analysis revealed that among these parameters, superior foraminal width was found to be significantly correlated with ODI and EQ-5D at the 1 year follow-up and with change in ODI and EQ-5D from baseline. The associations remained significant after adjustment for confounding factors including age, sex, body mass index, and duration of hospital stay. The results indicated that in degenerative lumbar foraminal stenosis, decreased superior foraminal width was associated with better improvement in disability and quality of life after TLIF.

Association of Body Mass Index with Long-Term All-Cause Mortality in Patients Who Had Undergone a Vertebroplasty for a Vertebral Compression Fracture.

We aimed to investigate the association between preoperative body mass index (BMI) and postoperative long-term mortality in patients who underwent a vertebroplasty. We retrospectively enrolled patients with a vertebral compression fracture who underwent a vertebroplasty between May 2013 and June 2020 in a medical center in Taiwan. The survival status of the study sample was confirmed by the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of being overweight/obese (≥25 kg/m2 vs. <25 kg/m2) and BMI (as a continuous variable) on all-cause mortality after adjusting for age, sex, history of smoking, diabetes, hypertension, chronic kidney disease, and osteoporosis. A total of 164 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.6%, mean BMI 24.0 ± 4.1 kg/m2) after a median follow-up of 785 days. Compared with a BMI < 25 kg/m2, a BMI ≥ 25 kg/m2 was associated with a significantly lower risk of all-cause mortality (HR 0.297, 95% CI 0.101 to 0.878, p = 0.028). These findings were consistent when BMI was examined as a continuous variable (HR 0.874, 95% CI 0.773 to 0.988, p = 0.031). A low BMI (<22 kg/m2) should be considered as a risk factor for postoperative long-term mortality in this ageing population.

Mutation in Drosophila concentrative nucleoside transporter 1 alters spermatid maturation and mating behavior.

Concentrative nucleoside transporters (Cnts) are unidirectional carriers that mediate the energy-costly influx of nucleosides driven by the transmembrane sodium gradient. Cnts are transmembrane proteins that share a common structural organization and are found in all phyla. Although there have been studies on Cnts from a biochemical perspective, no deep research has examined their role at the organismal level. Here, we investigated the role of the Drosophila melanogaster cnt1 gene, which is specifically expressed in the testes. We used the CRISPR/Cas9 system to generate a mutation in the cnt1 gene. The cnt1 mutants exhibited defects in the duration of copulation and spermatid maturation, which significantly impaired male fertility. The most striking effect of the cnt1 mutation in spermatid maturation was an abnormal structure of the sperm tail, in which the formation of major and minor mitochondrial derivatives was disrupted. Our results demonstrate the importance of cnt1 in male fertility and suggest that the observed defects in mating behavior and spermatogenesis are due to alterations in nucleoside transport and associated metabolic pathways.

Indirect decompression via oblique lumbar interbody fusion is sufficient for treatment of lumbar foraminal stenosis.

Oblique lumbar interbody fusion (OLIF) is a popular technique for the treatment of degenerative lumbar spinal disease. There are no clear guidelines on whether direct posterior decompression (PD) is necessary after OLIF. The purpose of this study was to analyze the effect of the indirect decompression obtained from OLIF in patients with lumbar foraminal stenosis. We retrospectively reviewed 33 patients who underwent OLIF surgery for degenerative lumbar spinal disease between 1 January 2018, and 30 June 2019. The inclusion criteria included patients who were diagnosed with lumbar foraminal stenosis by preoperative MRI. The exclusion criteria included the presence of central canal stenosis, spinal infection, vertebral fractures, and spinal malignancies. The clinical results, evaluated using the visual analogue scale of back pain (VAS-Back), VAS of leg pain (VAS-Leg), and Oswestry disability index (ODI), were recorded. The radiologic parameters were also measured. The VAS-Back, VAS-Leg, and ODI showed significant improvement in both the PD and non-posterior decompression (Non-PD) groups postoperatively (all, p < 0.05). Patients in the Non-PD group showed better results than those in the PD group in the VAS-Back at 12- and 24 months postoperatively (0.00 vs. 3.00 postoperatively at 12 months, p = 0.030; 0.00 vs. 4.00 postoperatively at 24 months, p = 0.009). In addition, the ODI at 24 months postoperatively showed better improvement in the Non-PD group (8.89 vs. 24.44, p = 0.038). The disc height in both the PD and the Non-PD groups increased significantly postoperatively (all, p < 0.05), but the restoration of foraminal height was significantly different only in the Non-PD group. There was no statistically significant difference in cage position, cage subsidence, fusion grade, or screw loosening between the PD and the Non-PD groups. Indirect decompression via OLIF for lumbar foraminal stenosis showed favorable outcomes. The use of interbody cages and posterior instrumentation was sufficient for relieving symptoms in patients with lumbar foraminal stenosis. Additional direct posterior decompression may deteriorate results in the follow-up period.

Robot-Assisted Pedicle Screw Placement Led to Lower Screw Loosening Rate than Fluoroscopy-Guided Technique in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disease: A Single-Center Retrospective Study.

Robot-assisted pedicle screw placement for spine surgery has become popular in recent years. This study compares clinical, radiographic outcomes and the screw loosening rate between robot-assisted and fluoroscopy-guided pedicle screw placement in patients who underwent transforaminal lumbar interbody fusion (TLIF). We retrospectively examined 108 patients with the degenerative lumbar disease who underwent TLIF. According to whether the robotic system was used, patients were assigned to either the robot-assisted (Ro TLIF, n = 29) or fluoroscopy-guided TLIF (FG TLIF, n = 79) group. Radiographic parameters and patient-reported outcomes, including leg and back pain visual analog scale (VAS) and Oswestry Disability Index (ODI), were assessed. Loosening signs were noted in 48 out of 552 pedicle screws. The screw loosening rate was higher in the FG TLIF (10.2%) than Ro TLIF group (4.3%). A significant correlation was found between screw loosening and age, the number of level(s) fused, and the ratio of the average distance from the pedicle screw to the upper endplate to vertebral body height. VAS-leg, VAS-back, and ODI showed significant improvements in both groups postoperatively (all p < 0.05). These results indicated that robot-assisted pedicle screw placement in TLIF had a lower screw loosening rate and similar patient-reported outcomes compared with the fluoroscopy-guided technique.

ENERGI-F703 gel, as a new topical treatment for diabetic foot and leg ulcers: A multicenter, randomized, double-blind, phase II trial.

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers. Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436. Findings: Starting from March 15th, 2017 to December 26th, 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment. Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations. Funding: Energenesis Biomedical Co., Ltd.

The Impact of COVID-19 Surges in 2019-2021 on Patient-Reported Outcome Measures After Spine Surgery at an Academic Tertiary Referral Center in Taiwan: A Retrospective Observational Cohort Study.

Aim: Limited data are available on the impact of the coronavirus disease 2019 (COVID-19) pandemic on patient-reported outcome measures (PROMs) in patients who underwent spine surgery. In this study, we aimed to investigate the associations between the COVID-19 outbreak in Taiwan (May 2021) and PROMs in patients who underwent spine surgery. Method: We retrospectively identified patients who underwent spine surgery during identical defined 6-week time-intervals (May 16 to June 30) in 2019, 2020, and 2021. PROMs, including visual analog scale (VAS) score for pain, Oswestry disability index (ODI), and EuroQol-5D (EQ-5D), were investigated before surgical intervention and at a 1-month follow-up. Relevant clinical information was collected from the electronic medical records of patients. Linear regression analysis was used to examine the association between the pandemic in 2021 (vs. 2019/2020) and the PROMs after adjusting for age, sex, and relevant clinical variables. Results: The number of patients who underwent spine surgery at our hospital during the identical defined 6-week time-intervals in 2019, 2020, and 2021 was 77, 70, and 48, respectively. The surgical intervention significantly improved VAS, ODI, and EQ-5D of the patients (1 month after surgery vs. before surgery, all p < 0.001) in all three study periods. However, there was a significant between-group difference in change from baseline in VAS (p = 0.002) and EQ-5D (p = 0.010). The decrease in VAS and increase in EQ-5D after surgery in 2021 were not as much as those in 2019 and 2020. The associations between the pandemic in 2021 (vs. 2019/2020) and changes in VAS (ß coefficient 1.239; 95% confidence interval [CI] 0.355 to 2.124; p = 0.006) and EQ-5D (ß coefficient, -0.095; 95% CI, -0.155 to -0.035; p = 0.002) after spine surgery were independent of relevant clinical factors. Conclusion: There was less improvement in short-term PROMs (VAS and EQ-5D) after spine surgery during the COVID-19 pandemic. Assessment of PROMs in surgical patients during a pandemic may be clinically relevant, and psychological support in this condition might help improve patients' outcomes.

Deformed wing virus infection affects the neurological function of Apis mellifera by altering extracellular adenosine signaling.

Deformed wing virus (DWV) infection is believed to be closely associated with colony losses of honeybee (Apis mellifera) due to reduced learning and memory of infected bees. The adenosine (Ado) pathway is important for maintaining immunity and memory function in animals, and it enhances antivirus responses by regulating carbohydrate metabolism in insects. Nevertheless, its effect on the memory of invertebrates is not yet clear. This study investigated how the Ado pathway regulates energy metabolism and memory in honeybees following DWV infection. Decreased Ado receptor (Ado-R) expression in the brain of infected bees resulted in a carbohydrate imbalance as well as impairments of glutamate-glutamine (Glu-Gln) cycle and long-term memory. Dietary supplementation with Ado not only increased the brain energy metabolism but also rescued long-term memory loss by upregulating the expression of memory-related genes. The present study demonstrated the regulation of the Ado pathway upon DWV infection and provides insights into the mechanisms underlying energy regulation and the neurological function of honeybees.

ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics.

Alterations of protein glycosylation are closely related with pathophysiological regulation. Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome. Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides. In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions. The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions. Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively. To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type. Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R. The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.

Ergosta-7,9(11),22-trien-3ß-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells.

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3ß-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.

Adenosine Receptor and Its Downstream Targets, Mod(mdg4) and Hsp70, Work as a Signaling Pathway Modulating Cytotoxic Damage in Drosophila.

Adenosine (Ado) is an important signaling molecule involved in stress responses. Studies in mammalian models have shown that Ado regulates signaling mechanisms involved in "danger-sensing" and tissue-protection. Yet, little is known about the role of Ado signaling in Drosophila. In the present study, we observed lower extracellular Ado concentration and suppressed expression of Ado transporters in flies expressing mutant huntingtin protein (mHTT). We altered Ado signaling using genetic tools and found that the overexpression of Ado metabolic enzymes, as well as the suppression of Ado receptor (AdoR) and transporters (ENTs), were able to minimize mHTT-induced mortality. We also identified the downstream targets of the AdoR pathway, the modifier of mdg4 (Mod(mdg4)) and heat-shock protein 70 (Hsp70), which modulated the formation of mHTT aggregates. Finally, we showed that a decrease in Ado signaling affects other Drosophila stress reactions, including paraquat and heat-shock treatments. Our study provides important insights into how Ado regulates stress responses in Drosophila.

Compromised Flap Salvage With Closed Incision Negative Pressure Therapy Under Real-Time Indocyanine Green Fluorescence Assessment.

BACKGROUND: Skin flap transfer is a commonly used technique by surgeons; however, compromised blood flow may result in flap ischemia and necrosis. We describe the use of closed incision negative pressure therapy (ciNPT) to help manage skin flap reconstructions with indocyanine green fluorescence angiography (ICG-FA) to assess perfusion of the flaps before and after ciNPT. METHODS: Three female and 5 male patients underwent various skin flap reconstructions, including local flaps, pedicled flaps, and propeller flaps, for wound defects related to trauma, infection, or cancer. After flap setting and suturing, ciNPT (-125 mm Hg) was applied to the closed incision for 7 days. Perfusion was assessed using ICG-FA before applying ciNPT and again at 24 hours later. The Shapiro-Wilk test and Wilcoxon signed rank test were used in statistical analysis. RESULTS: Initial postoperative survival was observed for all skin flaps; however, 1 flap failed after 2 weeks due to uncontrolled infection. The remaining 7 flaps healed well without any surgical revision. All patients were initially determined to have impaired flap perfusion; however, skin flap perfusion was significantly higher after ciNPT than before ciNPT in each case (P = 0.012). CONCLUSIONS: This study showed good healing outcomes for skin flap reconstructions without complications, despite the fact that each flap had compromised flap perfusion to some extent during the surgery. This case series is novel in that it used laser-assisted ICG-FA to provide a real-time assessment of skin flap perfusion before and after ciNPT.

Pipoxolan suppresses the inflammatory factors of NF-κB, AP-1, and STATs, but activates the antioxidative factor Nrf2 in LPS-stimulated RAW 264.7 murine macrophage cells.

Although pipoxolan (PIPO) is a smooth muscle relaxant, its anti-inflammatory capability has not been studied. Therefore, we investigated the anti-inflammatory molecular mechanisms of PIPO in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In this study, we used the MTT assay to evaluate the cytotoxicity, applied the enzyme-linked immunosorbent assay to determine the inflammatory cytokines, and performed Western blotting to assess protein expression. The results showed that PIPO significantly inhibited cytokine production, including nitric oxide, prostaglandin E2 , tumor necrosis factor-α, and interleukin-6. PIPO also suppressed the pro-inflammatory mediator expression with inducible nitric oxide synthase and cyclooxygenase-2. Moreover, PIPO prohibited the multiple inflammatory transcription factor pathways, including inhibitor kappa B/nuclear factor of the κ light chain enhancer of B cells (NF-κB), mitogen-activated protein kinase/activator protein-1 (AP-1), Janus kinase/signal transducer and activator of transcription (STAT), and toll-like receptor 4 (TLR4)/serine/threonine kinase (AKT). Besides, PIPO effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 antioxidative pathway. Collectively, PIPO may attenuate the inflammatory effects via influencing the LPS/TLR4 receptor binding; suppress the expression of anti-inflammatory transcription factors NF-κB, AP-1, and STAT; and activating the antioxidative transcription factor Nrf2 in LPS-stimulated mouse RAW 264.7 cells.