Association between pain and cognitive and daily functional impairment in older institutional residents: a cross-sectional study.

BACKGROUND: Pain is often neglected in disabled older population, especially in Taiwan where the population of institutional residents is rapidly growing. Our study aimed to investigate pain prevalence and associated factors among institutional residents to improve pain assessment and management. METHODS: This nationwide study recruited 5,746 institutional residents in Taiwan between July 2019 and February 2020. Patient self-report was considered the most valid and reliable indicator of pain. A 5-point verbal rating scale was used to measure pain intensity, with a score ranging from 2 to 5 indicating the presence of pain. Associated factors with pain, including comorbidities, functional dependence, and quality of life, were also assessed. RESULTS: The mean age of the residents was 77.1 ± 13.4 years, with 63.1% of them aged over 75 years. Overall, 40.3% of the residents reported pain, of whom 51.2% had moderate to severe pain. Pain was more common in residents with comorbidities and significantly impacted emotions and behavior problems, and the mean EQ5D score, which is a measure of health-related quality of life (p < .001). Interestingly, pain was only related to instrumental activities of daily living (IADL) and not activities of daily living (ADL). On the other hand, dementia was significantly negatively associated with pain (p < .001), with an estimated odds of 0.63 times (95% CI: 0.53-0.75) for the presence of pain when compared to residents who did not have dementia. CONCLUSIONS: Unmanaged pain is common among institutional residents and is associated with comorbidities, IADL, emotional/behavioral problems, and health-related quality of life. Older residents may have lower odds of reporting pain due to difficulty communicating their pain, even through the use of a simple 5-point verbal rating scale. Therefore, more attention and effort should be directed towards improving pain evaluation in this vulnerable population .

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

Hyperbaric Oxygen Therapy Alleviates Paclitaxel-Induced Peripheral Neuropathy Involving Suppressing TLR4-MyD88-NF-κB Signaling Pathway.

Paclitaxel (PAC) results in long-term chemotherapy-induced peripheral neuropathy (CIPN). The coexpression of transient receptor potential vanilloid 1 (TRPV1) and Toll-like receptor 4 (TLR4) in the nervous system plays an essential role in mediating CIPN. In this study, we used a TLR4 agonist (lipopolysaccharide, LPS) and a TLR4 antagonist (TAK-242) in the CIPN rat model to investigate the role of TLR4-MyD88 signaling in the antinociceptive effects of hyper-baric oxygen therapy (HBOT). All rats, except a control group, received PAC to induce CIPN. Aside from the PAC group, four residual groups were treated with either LPS or TAK-242, and two of them received an additional one-week HBOT (PAC/LPS/HBOT and PAC/TAK-242/HBOT group). Mechanical allodynia and thermal hyperalgesia were then assessed. The expressions of TRPV1, TLR4 and its downstream signaling molecule, MyD88, were investigated. The mechanical and thermal tests revealed that HBOT and TAK-242 alleviated behavioral signs of CIPN. Immunofluorescence in the spinal cord dorsal horn and dorsal root ganglion revealed that TLR4 overexpression in PAC- and PAC/LPS-treated rats was significantly downregulated after HBOT and TAK-242. Additionally, Western blots showed a significant reduction in TLR4, TRPV1, MyD88 and NF-κB. Therefore, we suggest that HBOT may alleviate CIPN by modulating the TLR4-MyD88-NF-κB pathway.

Autologous Fat Grafting in Female Genital Area Improves Sexual Function by Increasing Collagenesis, Angiogenesis, and Estrogen Receptors.

BACKGROUND: Vulvovaginal laxity, atrophic vaginitis, and orgasmic dysfunction are not only aesthetic but also sexual problems. Autologous fat grafting (AFG) facilitates tissue rejuvenation through the effects of adipose-derived stem cells; the fat grafts serve as soft-tissue filler. However, few studies have reported the clinical outcomes of patients undergoing vulvovaginal AFG. OBJECTIVES: The aim of this study was to describe a new technique, micro-autologous fat transplantation (MAFT), for AFG in the vulvovaginal area. Posttreatment histologic changes in the vaginal canal that imply improved sexual function were assessed. METHODS: This retrospective study enrolled females who underwent vulvovaginal AFG performed through MAFT between June 2017 and 2020. Assessments were based on the Female Sexual Function Index (FSFI) questionnaire and on histologic and immunohistochemical staining. RESULTS: In total, 20 female patients (mean age, 38.1 years) were included. On average, 21.9 mL of fat was injected into the vagina and 20.8 mL in the vulva and mons pubis area. Six months afterwards, the patients' mean total FSFI score (68.6) was significantly higher than that at baseline (43.8; P < .001). Histologic and immunohistochemical staining of vaginal tissues revealed substantially increased levels of neocollagenesis, neoangiogenesis, and estrogen receptors. By contrast, the level of protein gene product 9.5, which is associated with neuropathic pain, was considerably lower after AFG. CONCLUSIONS: AFG performed through MAFT in the vulvovaginal area may help manage sexual function-related problems in females. In addition, this technique improves aesthetics, restores tissue volume, alleviates dyspareunia with lubrication, and reduces scar tissue pain.

Spinal Irisin Gene Delivery Attenuates Burn Injury-Induced Muscle Atrophy by Promoting Axonal Myelination and Innervation of Neuromuscular Junctions.

Muscle loss and weakness after a burn injury are typically the consequences of neuronal dysregulation and metabolic change. Hypermetabolism has been noted to cause muscle atrophy. However, the mechanism underlying the development of burn-induced motor neuropathy and its contribution to muscle atrophy warrant elucidation. Current therapeutic interventions for burn-induced motor neuropathy demonstrate moderate efficacy and have side effects, which limit their usage. We previously used a third-degree burn injury rodent model and found that irisin-an exercise-induced myokine-exerts a protective effect against burn injury-induced sensory and motor neuropathy by attenuating neuronal damage in the spinal cord. In the current study, spinal irisin gene delivery was noted to attenuate burn injury-induced sciatic nerve demyelination and reduction of neuromuscular junction innervation. Spinal overexpression of irisin leads to myelination rehabilitation and muscular innervation through the modulation of brain-derived neurotrophic factor and glial-cell-line-derived neurotrophic factor expression along the sciatic nerve to the muscle tissues and thereby modulates the Akt/mTOR pathway and metabolic derangement and prevents muscle atrophy.

A comparison between cisatracurium and rocuronium-induced neuromuscular block on laryngeal electromyography recovery after neostigmine reversal in a porcine model.

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.

A Surgeon-Centered Neuromuscular Block Protocol Improving Intraoperative Neuromonitoring Outcome of Thyroid Surgery.

Background: Neuromuscular blocking agents provide muscular relaxation for tracheal intubation and surgery. However, the degree of neuromuscular block may disturb neuromuscular transmission and lead to weak electromyography during intraoperative neuromonitoring. This study aimed to investigate a surgeon-friendly neuromuscular block degree titrated sugammadex protocol to maintain both intraoperative neuromonitoring quality and surgical relaxation during thyroid surgery. Methods: A total of 116 patients were enrolled into two groups and underwent elective thyroid surgery with intraoperative neuromonitoring. All patients followed a standardized intraoperative neuromonitoring protocol with continuous neuromuscular transmission monitoring and received 0.6 mg/kg rocuronium for tracheal intubation. Patients were allocated into two groups according to the degree of neuromuscular block when the anterior surface of the thyroid gland was exposed. The neuromuscular block degree was assessed by the train-of-four (TOF) count and ratio. Patients in group I received sugammadex 0.25 mg/kg for non-deep neuromuscular block degree (TOF count = 1~4). Patients in group II were administered sugammadex 0.5 mg/kg for deep neuromuscular block degree (TOF count = 0). The quality of the intraoperative neuromonitoring was measured using the V1 electromyography (EMG) amplitude. An amplitude less than 500 µV and greater than 500 µV was defined as weak and satisfactory, respectively. Results: The quality of the intraoperative neuromonitoring was not different between groups I and II (satisfactory/weak: 75/1 vs. 38/2, P = 0.14). The quality of surgical relaxation was acceptable after sugammadex injection and showed no difference between groups [55/76 (72.3%) in group I vs. 33/40 (82.5%) in group II, P = 0.23]. Conclusions: This surgeon-centered sugammadex protocol guided by neuromuscular block degree (0.5 mg/kg for deep block and 0.25 mg/kg for others) showed comparably high intraoperative neuromonitoring quality and adequate surgical relaxation. The results expanded the practicality of sugammadex for precise neuromuscular block management during monitored thyroidectomy.

Dendrocorticiopsisorientalis gen. et sp. nov. of the Punctulariaceae (Corticiales, Basidiomycota) revealed by molecular data.

Dendrocorticiopsisorientalis is presented in this study as a new genus and new species based on morphological and phylogenetic evidence. This new taxon is characterized by resupinate, smooth and membranaceous basidiomata, monomitic hyphal system with clamps, colorless dendrohyphidia, variable presence of cystidia, and ellipsoid to ovoid basidiospores measuring 5-7 × 3.2-5.2 µm. The phylogenetic analyses based on the ITS1-5.8S-ITS2 (ITS) + nuclear 28S rDNA (28S) dataset of Corticiales indicated that the new taxon is nested in Punctulariaceae, separated from other genera with strong support values. Descriptions, specimen photo, and illustrations of the new taxon are provided in this study. A morphological comparison of the four genera of Punctulariaceae is given.

Hyperbaric Oxygen Therapy Attenuates Burn-Induced Denervated Muscle Atrophy.

Background: Neuronal apoptosis and inflammation in the ventral horn of the spinal cord contribute to denervated muscle atrophy post-burn. Hyperbaric oxygen therapy (HBOT) exerts anti-inflammation and neuroprotection. Furthermore, hypoxia-inducible factor (HIF)-1α has been reported to promote inflammation and apoptosis. We investigated the therapeutic potential of HBOT and the role of HIF-1α post-burn. Methods: Sprague-Dawley rats were divided into three groups: a control group, an untreated burn group receiving burn and sham treatment, and a HBOT group receiving burn injury and HBOT. The burn injury was induced with 75ºC ± 5ºC at the right hindpaw. HBOT (100% oxygen at 2.5 atmosphere, 90 min/day) and sham HBOT (21% oxygen at 1 atmosphere, 90 min/day) was started on day 28 after burn injury and continued for 14 treatments (days 28-41). Incapacitance (hind limb weight bearing) testing was conducted before burn and weekly after burn. At day 42 post-burn, the gastrocnemius muscle and the spinal cord ventral horn were analyzed. Results: HBOT improved burn-induced weight bearing imbalance. At day 42 post-burn, less gastrocnemius muscle atrophy and fibrosis were noted in the HBOT group than in the untreated burn group. In the ventral horn, HBOT attenuated the neuronal apoptosis and glial activation post-burn. The increases in phosphorylated AKT/mTOR post-burn were reduced after HBOT. HBOT also inhibited HIF-1α signaling, as determined by immunofluorescence and western blot. Conclusions: HBOT reduces burn-induced neuronal apoptosis in the ventral horn, possibly through HIF-1α signaling.

The First Whole Genome Sequencing of Sanghuangporus sanghuang Provides Insights into Its Medicinal Application and Evolution.

Sanghuangporus is a medicinal macrofungal genus typified by S. sanghuang, the very species utilized in traditional Chinese medicines by Chinese ancient people. To facilitate the medicinal application of S. sanghuang, we, for the first time, perform its genome sequencing and analyses from a monokaryon strain. A 33.34 Mb genome sequence was assembled to 26 contigs, which lead to the prediction of 8278 protein-coding genes. From these genes, the potential biosynthesis pathway of sesquiterpenoids was, for the first time, identified from Sanghuangporus, besides that of triterpenoids. While polysaccharides are the main medicinal metabolites in S. sanghuang, flavonoids are especially abundant medicinal metabolites comparing with other medicinal macrofungal groups. From the genomic perspective, S. sanghuang has a tetrapolar heterothallic mating system, and has its special nutritional strategy and advantageous medicinal properties compared with S. baumii and S. vaninii. A phylogenomics analysis indicates that Sanghuangporus emerged 15.39 million years ago and S. sanghuang has a closer phylogenetic relationship with S. baumii than S. vaninii. However, S. sanghuang shares a higher region of synteny and more orthologous genes, including carbohydrate-active enzymes with S. vaninii than S. baumii. A comparative genomics analysis with S. baumii and S. vaninii indicates that species diversification within Sanghuangporus may be driven by the translocation and translocation plus inversion of genome sequences, while the expansion and contraction of gene families may contribute to the host specificity of Sanghuangporus species. In general, the genome sequence of S. sanghuang provides insights into its medicinal application and evolution.

Optimization of electromyographic endotracheal tube electrode position by UEScope for monitored thyroidectomy.

OBJECTIVE: Proper position of an electromyographic (EMG) endotracheal tube within the larynx plays a key role in functional electrophysiologic intraoperative neural monitoring (IONM) in thyroid surgery. The purpose of this study was to determine the feasibility of a portable video-assisted intubation device (UEScope) to verify the optimal placement of an EMG tube. METHODS: A retrospective study enrolled 40 consecutive patients who underwent monitored thyroidectomies. After positioning the patient for surgery, an anesthesiologist performed tracheal intubation with UEScope and checked the position of the tube at the proper depth without rotation to the vocal cords. The main outcome measured was the proper EMG tube position, free from further adjustment. The secondary outcomes assessed were the percentage of available initial vagal stimulation (V1) signals. RESULTS: All tracheal intubations were successful at first attempt. Proper EMG tube placement without position adjustment was found in 97.5% of the patients. Tube withdrawal was required in a male patient. All patients obtained detectable V1 signals; the lowest and median V1 amplitude was 485 and 767 µV as a reference value, respectively. CONCLUSION: The UEScope is a valuable and reliable tool for placing an EMG tube and confirming its position during monitored thyroidectomy. In addition, further tube adjustment might be waived in most cases when the anesthesiologist placed the EMG tube after patient positioning for surgery. Routine use of video-assisted intubation devices is highly recommended. LEVEL OF EVIDENCE: 4.

Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang.

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 µmol·L-1, respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 µmol·L-1, respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.

Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt, and CaMKKß/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation.

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase ß (CaMKKß), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

Simultaneous hyperbaric oxygen therapy during systemic chemotherapy reverses chemotherapy-induced peripheral neuropathy by inhibiting TLR4 and TRPV1 activation in the central and peripheral nervous system.

BACKGROUND AND OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is considered one of the most common sequelae in patients with cancer who experience consistent abnormal sensations or pain symptoms during or after paclitaxel (PAC) chemotherapy. Transient receptor potential vanilloid 1 (TRPV1) and toll-like receptor 4 (TLR4) have been reported to interact in the nervous system in patients with CIPN. The antinociceptive effects of hyperbaric oxygen therapy (HBOT) on CIPN was demonstrated in this study through behavior tests. Using a CIPN rat model, we examined the effects of simultaneous HBOT (SHBOT) administration during chemotherapy and discovered that SHBOT achieved better reversal effects than chemotherapy alone. MATERIALS AND METHODS: Twenty-four rats were randomly allocated to four groups: control, PAC, SHBOT, and HBOT after PAC groups. Behavior tests were performed to evaluate mechanical allodynia and thermal hyperalgesia status. Tissues from the spinal cord and dorsal root ganglions were collected, and TLR4 and TRPV1 expression and microglial activation were investigated through immunofluorescence (IF) staining. RESULTS: The mechanical and thermal behavior tests revealed that HBOT intervention during PAC treatment led to the early alleviation of CIPN symptoms and inhibited CIPN deterioration. IF staining revealed that TLR4, TRPV1, and microglial activation were all upregulated in PAC-injected rats and exhibited early and significant downregulation in SHBOT-treated rats. CONCLUSION: This study is the first to demonstrate that the use of SHBOT during PAC treatment has potential for the early suppression of CIPN initiation and deterioration, indicating that it can alleviate CIPN symptoms and may reverse CIPN in patients undergoing systemic chemotherapy.

Synergic Effect of Botulinum Toxin Type A and Triamcinolone Alleviates Scar Pruritus by Modulating Epidermal Hyperinnervation: A Preliminary Report.

BACKGROUND: Patients often experience scar-related pruritus, which adversely affects quality of life. Triamcinolone acetonide (TAC) is widely used to treat pathologic scars, and botulinum toxin type A (BTX-A) reportedly improves scarring and associated discomfort. OBJECTIVES: The aim of this study was to investigate the clinical efficacy of combining TAC and BTX-A to reduce scar itch; potential mechanisms were investigated via an animal model. METHODS: For the clinical study, each scar on a patient was divided into 2 equal parts, with one part receiving TAC/BTX-A and the other TAC alone. Therapeutic interventions were administered over 3 sessions at 4-week intervals. Itch intensity was measured on a visual analog scale before each therapeutic intervention (V1, V2, V3) and 4 weeks after the last intervention (V4). For the animal model, rats were allocated into 5 groups: control, untreated burn, TAC, BTX-A, and TAC/BTX-A. We evaluated alloknesis in the right hind paw and analyzed possible molecular mechanisms. RESULTS: In humans, TAC/BTX-A significantly reduced scar itch compared with TAC alone at V4 (P = 0.04). In rats, post-burn itch was mitigated at 4 weeks after treatment with TAC, BTX-A, and TAC/BTX-A (P = 0.03, P = 0.0054, and P = 0.0053, respectively). TAC/BTX-A significantly decreased the density of intraepidermal nerve fibers post-burn relative to the untreated burn (P = 0.0008). TAC/BTX-A downregulated the expressions of nerve growth factor and protein transient receptor potential vanilloid subtype 1. CONCLUSIONS: TAC/BTX-A therapy exhibited enhanced and sustained clinical efficacy in relieving scar itch, possibly via modulating epidermal innervation and expression of transient receptor potential vanilloid subtype 1 .

Precision Neuromuscular Block Management for Neural Monitoring During Thyroid Surgery.

INTRODUCTION: Titration of neuromuscular block (NMB) plays a key role in intraoperative recurrent laryngeal nerve monitoring during thyroid surgery. The combination of neuromuscular blocking agent and timely partial reversal of NMB was investigated in both animal experiments and clinical neuro-monitored thyroidectomy. METHODS: In animal experiments, 8 piglets received sugammadex to assess the laryngeal EMG recovery after rocuronium-induced NMB. In clinical monitored thyroidectomy, 40 patients each were allocated to conventional group and sugammadex group. Conventional group received rocuronium 0.3 mg/kg at anesthesia induction, while sugammadex group received partial NMB recovery protocol- 0.6 mg/kg of rocuronium at anesthesia induction and 0.5 mg/kg of sugammadex. Main outcome was assessed by first (V1) and final (V2) EMG signal induced by vagal stimulation. RESULTS: In the porcine model, 50% recovery of laryngeal EMG amplitude was achieved at 16.8 ± 1.9 and 6 ± 2.7 minutes respectively after 0.5 and 1 mg/kg of sugammadex (p < 0.01). In monitored thyroidectomy, EMG amplitudes at V1 in group S and group C were 1214 ± 623 and 915 ± 476 µV, respectively (p = 0.02). Positive and adequately high EMG amplitudes were observed at the early surgical stage for all patients. Sugammadex groups were superior to conventional group in EMG tube placement (p < 0.001). CONCLUSION: Both porcine model and clinical application showed that precise NMB management by low-dose sugammadex was effective for intraoperative neural monitoring (IONM). The regimen ensured optimal conditions for tracheal intubation and timely neuromuscular function restoration for high-quality EMG signal.

Promotion of Bronchopulmonary Dysplasia Progression Using Circular RNA circabcc4 via Facilitating PLA2G6 Expression by Sequestering miR-663a.

Circular RNA (circRNA) has been increasingly proven as a new type of promising therapeutic RNA molecule in a variety of human diseases. However, the role of circRNA in bronchopulmonary dysplasia (BPD) has not yet been elucidated. Here, a new circRNA circABCC4 was identified from the Agilent circRNA chip as a differentially expressed circRNA in BPD. The relationship between circABCC4 level and BPD clinicopathological characteristics was analyzed. The function of circABCC4 was evaluated by performing CCK-8 and apoptosis analysis in vitro and BPD model analysis in vivo. RNA immunoprecipitation (RIP), luciferase reporter and rescue experiments were used to elucidate the interaction between circABCC4 and miR-663a. Luciferase reporter assay and rescue experiments were used to elucidate the interaction between PLA2G6 and miR-663a. CircABCC4 and PLA2G6 levels were increased, while miR-663a levels were decreased in the BPD group, compared to the control group. MiR-663a inhibited apoptosis by repressing PLA2G6 expression, while circABCC4 enhanced the apoptosis and inhibited the proliferation of A549 cells by sponging miR-663a and increasing PLA2G6 expression. In conclusion, circABCC4 promotes the evolving of BPD by spongening miR-663a and up-regulating PLA2G6 expression, which makes circABCC4 an ideal molecular target for early diagnosis and intervention of BPD.

Irisin Gene Delivery Ameliorates Burn-Induced Sensory and Motor Neuropathy.

Burn-related neuropathy is common and often involves pain, paresthesia, or muscle weakness. Irisin, an exercise-induced myokine after cleavage from its membrane precursor fibronectin type III domain-containing 5 (FNDC5), exhibits neuroprotective and anti-inflammatory activities. A rat model of third-degree burn on the right hind paw was used to investigate the therapeutic role of irisin/FNDC5. Rats received burn injury and were treated with intrathecal recombinant adenovirus containing the irisin sequence (Ad-irisin) at 3 weeks postburn. One week later, mechanical allodynia was examined. The expression of irisin in cerebrospinal fluid (CSF) was detected. Ipsilateral gastrocnemius muscle and lumbar spinal cord were also obtained for further investigation. Furthermore, the anti-apoptotic effect of recombinant irisin in SH-SY5Y cells was evaluated through tumor necrosis factor alpha (TNFα) stimulus to mimic burn injury. We noted intrathecal Ad-irisin attenuated pain sensitization and gastrocnemius muscle atrophy by modulating the level of irisin in CSF, and the expression of neuronal FNDC5/irisin and TNFα in the spinal cord. Ad-irisin also ameliorated neuronal apoptosis in both dorsal and ventral horns. Furthermore, recombinant irisin attenuated TNFα-induced SH-SY5Y cell apoptosis. In summary, irisin attenuated allodynia and muscle wasting by ameliorating neuroinflammation-induced neuronal apoptosis.

Combination Preemptive Peripheral Nerve Block in Limb Surgery. A Prospective Study.

Background and objectives: Patients often suffer from moderate to severe pain during the early recovery period in orthopedic surgery. We investigated the impact of a single-shot preoperative peripheral nerve block (PNB) on post-anesthesia recovery parameters and interleukin (IL)-6 level during limb surgery. Materials and Methods: A prospective randomized controlled study was conducted, and patients scheduled for limb surgery were recruited. Sixty patients were randomly assigned to either the PNB group or control group, who received morphine as a primary analgesic. The peak verbal numeric rating scale (NRS) score in the post-anesthesia care unit (PACU) was evaluated as a primary outcome. We also recorded rescue analgesics requirement and wake-up time from anesthesia in the PACU. In addition, the change of plasma IL-6 level after incision was measured. Results: Fifty-two patients completed the study, 27 and 25 cases in the PNB and control group, respectively. Preemptive PNB significantly reduced peak NRS score in the PACU compared to control group. Lower rescue analgesics requirement and rapid wake-up from anesthesia were also noted in PNB group. The IL-6 concentration increased less in the PNB group at 2 h after incision. Conclusions: Preemptive PNB attenuates IL-6 expression 2 h after incision and improves pain management in the PACU. PNB was considered as an essential part of pain management in limb surgery.

The Effectiveness of Low-dose Dexmedetomidine Infusion in Sedative Flexible Bronchoscopy: A Retrospective Analysis.

Background and objectives: Flexible bronchoscopy has been widely used for diagnosis and intervention, while various drugs are used for sedation during bronchoscopy. We examined two regular standardized sedation options (with or without dexmedetomidine) regularly used in our regional hospital. The aim was to assess the efficacy and safety of dexmedetomidine on conscious sedation under bronchoscopy. Materials and Methods: A retrospective chart review was conducted from April 2017 to March 2018. All patients undergoing flexible bronchoscopy with moderate sedation were enrolled. Patients having received dexmedetomidine-propofol-fentanyl were defined as group D, and those having received midazolam-propofol-fentanyl were defined as group M. The primary outcome was a safety profile during the procedure, including the incidence of procedural interference by patient cough or movement, transient hypoxemia, and hypotension. The secondary outcome was measured by the recovery profile (awake and ambulation time). Results: Thirty-five patients in group D and thirty-three in group M were collected in this retrospective study. All patients underwent the procedure successfully. Group D showed higher safety with fewer procedural interference incidences by cough or body movement than Group M (3.3% versus 36.3%, p < 0.001) and minor respiratory adverse effects. Patients in group D showed faster recovery in a shorter ambulation time than group M (24.9 ± 9.7 versus 31.5 ± 11.9, p = 0.02). In group D, bronchoscopist satisfaction to sedation was higher than group M (p = 0.01). More transient bradycardia episodes were noted in patients receiving dexmedetomidine (p < 0.05), but all recovered without atropine intervention. Overall post-procedural adverse events and satisfaction were comparable in the two groups. Conclusions: The co-administration of dexmedetomidine met the safety and recovery demands of flexible bronchoscopy. Compared to the conventional midazolam-propofol-fentanyl regimen, the application of dexmedetomidine improved sedative effectiveness with less procedural interruptions, shorter time to ambulation and higher bronchoscopist satisfaction.