Surgical outcomes of modified versus conventional transoral endoscopic thyroidectomy vestibular approach for papillary thyroid carcinoma.

Injectable chitosan-based hydrogel via in situ gelation modulates the inflammatory microenvironment and facilitates minimally invasive repair of peripheral nerve injury.

Mid-term outcomes of the Latarjet procedure for shoulder instability: A retrospective study of 187 shoulders with an eight-year follow-up.

Diagnostic performance of AI-assisted intraoperative imaging for parathyroid identification: a systematic review.

Intraneural delivery of CBD3A6K-RhB via PEG-PLGA nanoparticles for neuropathic pain therapy.

Vocal fold movement impairment and aspiration risk in children undergoing aerodigestive surgery.

Patients with peripheral nerve injury (PNI) often experience neuropathic pain (NP), which is difficult to treat effectively due to ongoing inflammation and oxidative stress that impede nerve repair. Traditional anti-inflammatory antioxidants are limited by short half-lives and significant side effects. This study introduces a supramolecular hydrogel formed by combining anti-inflammatory betamethasone phosphate (Betp) with calcium chloride to create betamethasone phosphate hydrogel (Betp@Gel). The antioxidant curcumin (Cur) was incorporated into this gel to form Cur/Betp@Gel, which can be injected directly at the injury site for sustained Cur release. Cur/Betp@Gel demonstrates superior sustained-release capabilities and therapeutic effectiveness compared to Betp@Gel or Cur alone. It enhances pain relief, supports functional recovery after nerve damage, and promotes nerve repair and regeneration. This is achieved by Betp@Gel's anti-inflammatory effects, which inhibit TNF-α, IL-1β, and IL-6, combined with Cur's continuous slow release, which scavenges reactive oxygen species (ROS). Additionally, Cur/Betp@Gel mitigates PNI-induced spinal inflammation by reducing GFAP and Iba-1 expression in the spinal cord. Overall, in-situ injection of Cur/Betp@Gel is a promising strategy for aiding nerve repair and alleviating neuropathic pain.

Glaucoma is a multi-factorial degenerative optic neuropathy disease. The core pathological change caused by various etiologies is the death of retinal ganglion cells (RGCs). Oxidative stress response is one of the important microscopic mechanisms through which glaucoma mechanically damages RGCs. Scutellarin (SCU) is a flavonoid glycoside extracted from the traditional Chinese medicinal material Erigeron breviscapus. It has been proven to exert various pharmacological effects, such as anti-inflammatory, antioxidant, anti-tumor, and anti-neurodegenerative effects. However, its role in protecting the optic nerve in glaucoma remains unclear. This study aims to identify the specific mechanism of SCU on the R28 cell injury model induced by continuous hydrostatic pressure (CHP) combined with oxygen-glucose deprivation (OGD). The continuous hydrostatic pressure device was placed in a tri-gas incubator, which was set to maintain a stable, humidified environment at 37°C with 5 % CO2, 1 % O2, and 94 % N2. A model was then created under a continuous hydrostatic pressure of 150 mbar for 24 h to simulate the pathological changes of optic nerve injury under high intraocular pressure conditions, mimicking chronic glaucoma. Cell viability, morphology, apoptosis, and histological changes were subsequently observed. To further investigate the molecular mechanisms, CCK8 assays, ROS assays, flow cytometry, EdU assays, immunofluorescence staining, and Western blots were performed. Following CHP combined with OGD injury modeling, the expression of ROS and the oxidative stress injury gene 4-HNE was significantly increased. Concurrently, Keap1, a key upstream negative regulator of Nrf2, showed increased expression, while nuclear Nrf2 expression decreased, and the expression of the antioxidant factor HO-1 increased. Furthermore, the expression of p-IKKβ, p-IκBα, and p-p65 was significantly enhanced, indicating the activation of the Nf-kB signaling pathway. The expression of key apoptotic factors Bax and C-caspase-3 was elevated, while Bcl-2 expression was reduced. After SCU intervention, R28 cell proliferation was effectively promoted through the inhibition of oxidative stress. This intervention significantly inhibited the expression of ROS and 4-HNE, decreased Keap1 expression, and increased nuclear Nrf2 expression, thereby further promoting the elevated expression of the antioxidant defense gene HO-1. SCU also significantly inhibited the expression of p-IKKβ, p-IκBα, and p-p65, synergistically regulating and activating the Keap1/Nrf2 pathway, and inhibiting the Nf-κB pathway, thereby further downregulating the expression of apoptosis factors Bax and C-caspase-3, and upregulating Bcl-2 expression. This study demonstrated that in the R28 cell injury model induced by continuous hydrostatic pressure combined with oxygen-glucose deprivation, SCU can promote the proliferation of R28 cells and reduce the expression of apoptotic factors through the antioxidant stress effect mediated by the Keap1/Nrf2/Nf-κB signaling pathway. This finding provides a potentially effective candidate compound and a mechanistic approach for the drug treatment of glaucoma optic nerve protection.

Hydrogen-releasing electroactive nerve guidance conduits promote peripheral nerve regeneration by remodeling the microenvironment.

The majority of dorsal root ganglion neurons are excitatory glutamatergic neurons. Recent studies suggest that a subset of dorsal root ganglion neurons are able to synthesize γ-aminobutyric acid (GABA) and are immunoreactive to vesicular GABA transporter (Vgat) that packages GABA into the synaptic vesicles critical for inhibitory neurotransmission. The current study aimed to investigate the spinal circuits innervated by these Vgat + primary sensory neurons and interrogate the role of Vgat + primary sensory neurons in nociceptive modification. The authors used viral tracings, immunohistochemistry, patch clamp electrophysiologic recordings, optogenetics, chemogenetics, and behavioral assays in male Vgat-Cre mice to dissect the anatomical connectivity and function of Vgat + primary sensory neurons. The data showed that the central terminals of Vgat + primary sensory neurons made inhibitory connections with spinal cord somatostatin-positive excitatory interneurons and meanwhile formed glutamatergic connections with local GABAergic interneurons driving feedforward inhibition. The functional dichotomy of Vgat + primary sensory neurons constituted an inhibitory spinal circuit that prevented aversive and pain-like responses of mice to innocuous or noxious mechanical stimuli. After peripheral nerve injury, the reduction of inhibitory drive from Vgat + primary sensory neurons to spinal somatostatin-positive interneurons correlated with mechanical nociceptive sensitization. Optogenetic or chemogenetic stimulation of Vgat + primary sensory neurons effectively alleviated the nerve injury-induced hypersensitivity to mechanical stimulation. The data suggested that the Vgat + primary sensory neurons innervating a discrete spinal microcircuit were ideally suited to suppress the mechanical pain transmission.

Shati/nat8l catalyzes the synthesis of N-acetylaspartate (NAA), a precursor for N-acetylaspartylglutamate (NAAG), an endogenous agonist of group II metabotropic glutamate receptor 3 (mGluR3). Although spinal mGluR3 is known to modulate nociceptive signaling, the functional role of Shati/nat8l in pain transmission has remained unclear. In this study, we investigated the involvement of spinal Shati/nat8l in mechanical nociceptive processing and neuropathic pain. We found that Shati/nat8l knockout (Shati-/-) mice exhibited a significantly decreased mechanical pain threshold compared to wild-type controls. This hypersensitivity was reversed by adeno-associated virus (AAV)-mediated expression of Shati/nat8l in the spinal dorsal horn. Intrathecal administration of NAAG-but not NAA-restored mechanical thresholds in Shati-/- mice, and this effect was blocked by the group II mGluR antagonist LY341495. In addition, treatment with LY341495 showed antinociceptive effect in normal mice at higher doses. In a peripheral nerve injury model, expression of Shati/nat8l mRNA in the ipsilateral dorsal horn was significantly decreased. Importantly, AAV-mediated restoration of Shati/nat8l expression in the dorsal horn alleviated neuropathic mechanical hyperalgesia and normalized Shati/nat8l mRNA levels. These findings suggest that downregulation of spinal Shati/nat8l contributes to mechanical hypersensitivity by impairing the NAAG-mGluR3 signaling pathway. Targeting the Shati/nat8l-NAAG-mGluR3 axis may offer a novel therapeutic strategy for the treatment of neuropathic pain.

Modulation of glutamate metabolic reprogramming via Ras-Raf-MEK/ERK signaling alleviates immune inflammation of astrocytes in glaucomatous neurodegeneration.

Persistent neuropathic pain selectively impairs hedonic and motivational aspects of eating: Insights from a mouse model.

NLRP10 ablation alleviates neuropathic pain by inhibiting excessive NIX/LC3-dependent mitophagy in the spinal cord.

Bioinks used in the repair of nerve injury in vivo

Diabetic Neuropathy (DN) is a long-term persistent neuro impairment associated with Type 2 Diabetes Mellitus (T2DM). DN develops when chronic hyperglycaemia damages peripheral and autonomic nerves, giving rise to a broad spectrum of clinical symptoms. The mechanism of DN is elaborate and multicomponent, mediated by persistent hyperglycaemia, lipid metabolic dysfunction, oxidative imbalance, impaired mitochondrial activity, and neuroinflammation, together giving rise to progressive peripheral nerve injury. Persistently raised glucose levels promote the accumulation of glycotoxins, leading to alteration in protein synthesis and function. Inflammatory mediators such as Interleukin-6 (IL-6), C-Reactive Protein (CRP), IL-18, IL-8, and Tumour Necrosis Factor alpha (TNF-α) further amplify nerve damage by activating Nuclear Factor kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Modern strategies for managing DN focus on glycaemic control, lifestyle modifications, and emerging treatments namely Sodium-Glucose Cotransporter 2 (SGLT2) targeting drugs and Glucagon-Like Peptide-1 (GLP-1) mimetic. Further the identification of biochemical markers and molecular targets may facilitate early diagnosis and enable more personalised interventions. Continued collaboration between basic science scientists and clinicians will be essential in translating biochemical insights into tangible benefits for individuals. Despite our growing knowledge of the complexity of DN has sustainably improved in prior years, yet such knowledge of biochemical aspects and earlier predictor of neuropathy associated with diabetes are not entirely clear. Hence, the present review tends to describe the present comprehension about biochemical aspects, mechanism of neurological progression, and interconnected pathways involved in DN.

This study aims to evaluate the effects of poly(3-hydroxybutyrate)/alginate (PHBA/ALG) tubular graft containing cytidine 5'-diphosphocholine (citicoline) on axonal regeneration in an experimental rat sciatic nerve injury model and to compare the results of this method with autologous nerve grafting. A total of 24 Wistar-Hannover albino rats were randomly divided into three groups (n=8). In all animals, a 10 mm segment was removed from the right sciatic nerve under microscope. The nerve defect was repaired using autologous nerve graft (group O), PHBA graft only (group T), and PHBA graft containing citicoline (group S). Sixteen weeks later, all animals were euthanized and sciatic nerve samples were taken for histopathological examination. Sections were stained with hematoxylin-eosin and Masson Trichrome. The groups were compared statistically in terms of regenerated axon diameter, number of blood vessels, nerve sheath degeneration, edema, inflammatory cell infiltration, and necrosis. Histopathological evaluation showed that regenerative axons were formed in all three groups. PHBA and citicoline-containing PHBA grafts successfully bridged the damaged area. While the best results were obtained in the autograft group, the results of the PHBA group containing citicoline were statistically significantly better than the PHBA group. In general, the distribution of histopathological parameters showed that citicoline administration showed protective effects on parameters such as inflammation and cell death. Axon diameter : group S had significantly larger axon diameters than group T (p<0.05). Number of blood vessels : the highest values were in the autograft group and the difference between groups O and T was significant (p<0.05). PHBA-based tubular graft with oriented nanofiber structure containing citicoline supports peripheral nerve regeneration. Although our results are not better than autograft, it may be a promising alternative for cases where autologous graft is not available.

As an emerging therapeutic option for erectile dysfunction (ED), low-intensity pulsed ultrasound (LIPUS) has attracted increasing attention. The therapeutic effect of LIPUS is comparable to low-intensity extracorporeal shockwave therapy. However, the underlying mechanism of LIPUS remains unclear. We summarized the current literature to assess the efficacy of LIPUS for ED and elucidate the biological effects caused by LIPUS in different ED models. Preliminary clinical studies demonstrate that LIPUS is beneficial for ED with varying degrees of severity, and its therapeutic effect can be enhanced when combined with phosphodiesterase 5 inhibitors. Basic researches have shown that LIPUS can treat ED resulting from type 1 diabetes mellitus, cavernous nerve injury, or cavernosa injury. The underlying mechanisms involve upregulating endothelial and neuronal nitric oxide synthase expression, increasing smooth muscle and endothelium content, inhibiting cavernosal fibrosis mediated by the transforming growth factor-β1/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β1/Smad/CTGF) pathway, and ameliorating oxidative stress via microtubule-associated protein 1 light chain 3 (LC3)- and Parkin-dependent mitophagy in type 1 diabetic ED. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), activated by LIPUS, contribute to the recovery of neurogenic ED. Furthermore, the survival and secretion function of Schwann cells are improved by LIPUS through activating tropomyosin receptor kinase B/protein kinase B/cyclic adenosine monophosphate-response element-binding protein (TrkB/Akt/CREB) pathway, thereby accelerating cavernous nerve repair. LIPUS is a safe and effective treatment modality for ED, which can restore the pathological changes in corpus cavernosum via multiple pathways. The long-term efficacy of LIPUS needs further investigation.

Lower Extremity Nerve Injury During Labor and Birth: AWHONN Practice Brief Number 11.

Puerarin promotes nerve regeneration and functional recovery after peripheral nerve injury by inhibiting ACSL4-dependent ferroptosis.