Unraveling the protein post-translational modification landscape: Neuroinflammation and neuronal death after stroke.

The impact of stroke on global health is profound, with both high mortality and morbidity rates. This condition can result from cerebral ischemia, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). The pathophysiology of stroke involves secondary damage and irreversible loss of neuronal function. Post-translational modifications (PTMs) have been recognized as crucial regulatory mechanisms in ischemic and hemorrhagic stroke-induced brain injury. These PTMs include phosphorylation, glycosylation, ubiquitination, SUMOylation, acetylation, and succinylation. This comprehensive review delves into recent research on the PTMs landscape associated with neuroinflammation and neuronal death specific to cerebral ischemia, ICH, and SAH. This review aims to explain the role of PTMs in regulating pathologic mechanisms and present critical techniques and proteomic strategies for identifying PTMs. This knowledge helps us comprehend the underlying mechanisms of stroke injury and repair processes, leading to the development of innovative treatment strategies. Importantly, this review underscores the significance of exploring PTMs to understand the pathophysiology of stroke.

The role of metal ions in stroke: Current evidence and future perspectives.

Metal ions play a pivotal role in maintaining optimal brain function within the human body. Nevertheless, the accumulation of these ions can result in irregularities that lead to brain damage and dysfunction. Disruptions of metal ion homeostasis can result in various pathologies, including inflammation, redox dysregulation, and blood-brain barrier disruption. While research on metal ions has chiefly focused on neurodegenerative diseases, little attention has been given to their involvement in the onset and progression of stroke. Recent studies have identified cuproptosis and confirmed ferroptosis as significant factors in stroke pathology, underscoring the importance of metal ions in stroke pathology, including abnormal ion transport, neurotoxicity, blood-brain barrier damage, and cell death. Additionally, it provides an overview of contemporary metal ion chelators and detection techniques, which may offer novel approaches to stroke treatment.

Causal associations between frailty and low back pain: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Previous observational studies have revealed a potentially robust bidirectional relationship between frailty and low back pain (LBP). However, the precise causal relationship remains unclear. METHODS: To examine the potential causal association between frailty and LBP, we conducted bidirectional two-sample Mendelian randomization analysis (MR) study. Genetic data on frailty index (FI) and LBP were acquired from publicly available genome-wide association studies (GWAS). Various MR methodologies were utilized, such as inverse variance weighting (IVW), weighted median, and MR-Egger, to evaluate causality. Additionally, sensitivity analyses were conducted to evaluate the robustness of the findings. RESULTS: Genetically predicted higher FI (IVW, odds ratio [OR] = 1.66, 95% CI 1.17-2.36, p = 4.92E-03) was associated with a higher risk of LBP. As for the reverse direction, genetic liability to LBP showed consistent associations with a higher FI (IVW, OR = 1.13, 95% CI 1.07-1.19, p = 2.67E-05). The outcomes from various MR techniques and sensitivity analyses indicate the robustness of our findings. CONCLUSION: Our research findings provide additional evidence bolstering the bidirectional causal relationship between frailty and LBP.

The extracapsular capsule phenomenon of percutaneous balloon compression provides adequate compression of the third branch of the trigeminal nerve: a retrospective study.

BACKGROUND: Percutaneous balloon compression (PBC) is an effective, low-cost, and simple treatment for primary trigeminal neuralgia (TN). However, PBC has poor efficacy and no better solution for the third branch (V3) of TN. METHODS: Clinical data of 52 patients with trigeminal neuralgia treated with PBC were retrospectively analyzed. Postoperative numbness of the patient was evaluated by facial numbness at the Barrow Neurological Institute (BNI-N). The main observation was the incidence of higher numbness in the V3 than in the other two branches or equally strong numbness in the three branches in the immediate postoperative period. RESULTS: The efficacy values in the pear-shaped balloon group at the first postoperative day (T1), the first month (T2), in the third month (T3), and the sixth month (T4) were 96.7%, 93.3%, 93.3%, and 90%, respectively, and 1 patient (3.3%) had recurrence. The efficacy value for the extracapsular capsule group was 95.5% at all times and there were no patients with recurrence within 6 months after surgery. In the immediate postoperative period, the effective compression rate of V3 in the pear-shaped balloon group was 43.3%, and 86.4% in the extracapsular capsule group (P = 0.020). At six months of follow-up, the effective compression rate of V3 was higher in the extracapsular capsule group than in the pear-shaped balloon group. CONCLUSIONS: The riveted structure of the extracapsular capsule can effectively compress V3, thus performing PBC with a balloon shaped as an extracapsular capsule is a new, effective, and safe treatment option for TN V3. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2300067313.

Immune-mediated disruption of the blood-brain barrier after intracerebral hemorrhage: Insights and potential therapeutic targets.

AIMS: Intracerebral hemorrhage (ICH) is a condition that arises due to the rupture of cerebral blood vessels, leading to the flow of blood into the brain tissue. One of the pathological alterations that occurs during an acute ICH is an impairment of the blood-brain barrier (BBB), which leads to severe perihematomal edema and an immune response. DISCUSSION: A complex interplay between the cells of the BBB, for example, pericytes, astrocytes, and brain endothelial cells, with resident and infiltrating immune cells, such as microglia, monocytes, neutrophils, T lymphocytes, and others accounts for both damaging and protective mechanisms at the BBB following ICH. However, the precise immunological influence of BBB disruption has yet to be richly ascertained, especially at various stages of ICH. CONCLUSION: This review summarizes the changes in different cell types and molecular components of the BBB associated with immune-inflammatory responses during ICH. Furthermore, it highlights promising immunoregulatory therapies to protect the integrity of the BBB after ICH. By offering a comprehensive understanding of the mechanisms behind BBB damage linked to cellular and molecular immunoinflammatory responses after ICH, this article aimed to accelerate the identification of potential therapeutic targets and expedite further translational research.

Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study.

Background: Frailty has been associated with mental illness (MI) observational studies, but the causal relationship between these factors remains uncertain. We aimed to assess the bidirectional causality between frailty and MI by two-sample Mendelian randomization (MR) analyses. Methods: To investigate the causal relationship among them, summary statistics of frailty index (FI) and six types of MI: anxiety, depression, affective disorder, mania, schizophrenia, and obsessive-compulsive disorder (OCD) were included in this MR study. This MR analysis was performed using inverse variance weighting (IVW), MR-Egger regression, and weighted median. The stability of the results was evaluated using Cochran's Q test, MR-Egger intercept test, Funnel Plots, and leave-one-out analysis. Results: Genetic predisposition to FI was significantly associated with increased anxiety (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.13-2.33, P = 8.18E-03), depression (OR = 1.88, 95% CI 1.30-2.71, P = 8.21E-04), affective disorder (OR = 1.70, 95% CI 1.28-2.27, P = 2.57E-04). However, our study findings do not demonstrate a causal relationship between FI and mania (OR = 1.02, 95% CI 0.99-1.06, P = 2.20E-01), schizophrenia (OR = 1.02, 95% CI 0.07-0.86, P = 9.28E-01). In particular, although the IVW results suggest a potential causal relationship between FI and OCD (OR = 0.64, 95% CI 0.07-0.86, P = 2.85E-02), the directions obtained from the three methods we employed ultimately show inconsistency. Therefore, the result must be interpreted with caution. The results of the reverse MR analysis indicated a statistically significant and causal relationship between anxiety (OR = 1.06, 95% CI 1.01-1.11, P = 2.00E-02), depression (OR = 1.14, 95% CI 1.04-1.26, P = 7.99E-03), affective disorder (OR = 1.15, 95% CI 1.09-1.21, P = 3.39E-07), and schizophrenia (OR = 1.02, 95% CI 1.01-1.04, P = 1.70E-03) with FI. However, our findings do not provide support for a link between mania (OR = 1.46, 95% CI 0.79-2.72, P = 2.27E-01), OCD (OR = 1.01, 95% CI 1.00-1.02, P = 2.11E-01) and an increased risk of FI. Conclusion: The MR results suggest a potential bidirectional causal relationship between FI and anxiety, depression, and affective disorder. Schizophrenia was found to be associated with a higher risk of FI. The evidence was insufficient to support a causal relationship between Fl and other Ml. These findings offer new insights into the development of effective management strategies for frailty and MI.

Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury.

Nanozymes, which can selectively scavenge reactive oxygen species (ROS), have recently emerged as promising candidates for treating ischemic stroke and traumatic brain injury (TBI) in preclinical models. ROS overproduction during the early phase of these diseases leads to oxidative brain damage, which has been a major cause of mortality worldwide. However, the clinical application of ROS-scavenging enzymes is limited by their short in vivo half-life and inability to cross the blood-brain barrier. Nanozymes, which mimic the catalytic function of natural enzymes, have several advantages, including cost-effectiveness, high stability, and easy storage. These advantages render them superior to natural enzymes for disease diagnosis and therapeutic interventions. This review highlights recent advancements in nanozyme applications for ischemic stroke and TBI, emphasizing their potential to mitigate the detrimental effect of ROS overproduction, oxidative brain damage, inflammation, and blood-brain barrier compromise. Therefore, nanozymes represent a promising treatment modality for ROS overproduction conditions in future medical practices.

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.

Cav3.2 T-Type calcium channels downregulation attenuates bone cancer pain induced by inhibiting IGF-1/HIF-1α signaling pathway in the rat spinal cord.

Background: Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated. Methods: The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2. Results: The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP. Conclusion: These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway.

Blocking autofluorescence in brain tissues affected by ischemic stroke, hemorrhagic stroke, or traumatic brain injury.

Autofluorescence is frequently observed in animal tissues, interfering with an experimental analysis and leading to inaccurate results. Sudan black B (SBB) is a staining dye widely used in histological studies to eliminate autofluorescence. In this study, our objective was to characterize brain tissue autofluorescence present in three models of acute brain injury, including collagenase-induced intracerebral hemorrhage (ICH), traumatic brain injury (TBI), and middle cerebral artery occlusion, and to establish a simple method to block autofluorescence effectively. Using fluorescence microscopy, we examined autofluorescence in brain sections affected by ICH and TBI. In addition, we optimized a protocol to block autofluorescence with SBB pretreatment and evaluated the reduction in fluorescence intensity. Compared to untreated, pretreatment with SBB reduced brain tissue autofluorescence in the ICH model by 73.68% (FITC), 76.05% (Tx Red), and 71.88% (DAPI), respectively. In the TBI model, the ratio of pretreatment to untreated decreased by 56.85% (FITC), 44.28% (Tx Red), and 46.36% (DAPI), respectively. Furthermore, we tested the applicability of the protocol using immunofluorescence staining or Cyanine-5.5 labeling in the three models. SBB treatment is highly effective and can be applied to immunofluorescence and fluorescence label imaging techniques. SBB pretreatment effectively reduced background fluorescence but did not significantly reduce the specific fluorescence signal and greatly improved the signal-to-noise ratio of fluorescence imaging. In conclusion, the optimized SBB pretreatment protocol blocks brain section autofluorescence of the three acute brain injury models.

Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies.

The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.

Neutrophil autophagy and NETosis in COVID-19: perspectives.

The COVID-19 pandemic has caused substantial losses worldwide in people's lives, health, and property. Currently, COVID-19 is still prominent worldwide without any specific drug treatment. The SARS-CoV-2 pathogen is the cause of various systemic diseases, mainly acute pneumonia. Within the pathological process, neutrophils are recruited to infected sites, especially in the lungs, for the first stage of removing invading SARS-CoV-2 through a range of mechanisms. Macroautophagy/autophagy, a conserved autodegradation process in neutrophils, plays a crucial role in the neutrophil phagocytosis of pathogens. NETosis refers to neutrophil cell death, while auto-inflammatory factors and antigens release NETs. This review summarizes the latest research progress and provides an in-depth explanation of the underlying mechanisms of autophagy and NETosis in COVID-19. Furthermore, after exploring the relationship between autophagy and NETosis, we discuss potential targets and treatment options. This review keeps up with the latest research on COVID-19 from neutrophil autophagy and NETosis with a new perspective, which can guide the urgent development of antiviral drugs and provide guidance for the clinical treatment of COVID-19.Abbreviations: AKT1: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; AP: autophagosome; ARDS: acute respiratory distress syndrome; ATG: autophagy related; BECN1: beclin 1; cfDNA: cell-free DNA; COVID-19: coronavirus disease 2019; CQ: chloroquine; DMVs: double-membrane vesicles; ELANE/NE: elastase, neutrophil expressed; F3: coagulation factor III, tissue factor; HCQ: hydroxychloroquine; MAP1LC3/LC3: microtubule associated protein 1 light chain of 3; MPO: myeloperoxidase; MTORC1: mechanistic target of rapamycin kinase complex 1; NETs: neutrophil traps; NSP: nonstructural protein; PI3K: class I phosphoinositide 3-kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SKP2: S-phase kinase associated protein 2; TCC: terminal complement complex; ULK1: unc-51 like.

Meckel's Cave Size Measured by Magnetic Resonance Imaging in the Prognosis of Percutaneous Balloon Compression for Trigeminal Neuralgia.

BACKGROUND: Percutaneous balloon compression (PBC) is a safe and effective method to treat trigeminal neuralgia. Despite it is known that intraoperative balloon volume is crucial in the prognosis of PBC patients and correlates with Meckel's cave (MC) size, it is a lack of objective and valid criteria for intraoperative balloon volume of PBC. OBJECTIVES: The aim of this study was to evaluate the relationship between the size of MC and the volume of a pear-shaped balloon in improving the prognosis of patients receiving PBC. STUDY DESIGN: Retrospective study. METHODS: Patients were divided into 3 groups according to their prognosis, and simple linear regression equations were established separately. Group A was defined as having recurrence. Group B was defined as having no recurrence and a Barrow Neurological Institute facial numbness (BNI-N) score of 2 with no recurrence. Correlation analysis was carried out to determine the association of the intraoperative balloon volume with MC size. We attempted to construct simple linear regression models after verifying that both parameters were in compliance with the requirements of this model. RESULTS: Until the end of the 6-months follow-up, 60 patients (93.8%) reported no pain, and 4 patients (6.3%) experienced no significant pain relief. Sixteen (25.0%) patients had severe facial numbness, 48 (75.0%) patients had no facial numbness or had only mild numbness. All 3 groups had a significant correlation between balloon volume and MC size. Group A: Balloon volume (cm3) = -0.371 + 1.883*MC size (R2 = 0.882); Group B: Balloon volume (cm3) = 0.110 + 1.274*MC size (R2 = 0.861); and Group C: Balloon volume (cm3) = 0.011 + 1.835*MC size (R2 = 0.857). LIMITATIONS: The main limitation of our study is its observational retrospective nature, and we were unable to further analyze the intraoperative balloon pressure and volume, as well as validate the accuracy of the model. In additional this was a single-center study with a small sample size and a short follow-up period. These may have contributed to the bias in the final results. A multicenter, prospective study with a large sample size should be performed to further investigate the long-term effects of individualized balloon volumes and the correlation between pressures. CONCLUSIONS: The equation [balloon volume (cm3) = 0.110 cm3 + 1.274*MC size] yields an appropriate value at which the patient has a low recurrence rate and a low degree of facial numbness. Preoperative measurement of MC size can be used to guide the intraoperative balloon volume and to predict the patient's prognosis.

Short-term spinal cord stimulation is an effective therapeutic approach for herpetic-related neuralgia-A Chinese nationwide expert consensus.

Purpose: Short-term spinal cord stimulation (st-SCS) has been widely used to treat herpetic-related neuralgia (HN) in China for several years, but is still heavily debated as it has no strong evidence in clinical application. Therefore, a questionnaire survey among the Chinese pain specialist workgroup of the Chinese Neuromodulation Society and Chinese Medical Doctor Association was carried out to achieve a consensus about the clinical use of st-SCS for HN treatment. Methods: The contents of the questionnaire include basic information about doctors (hospital level, work experience, training, procedure numbers, etc.), efficacy, indications, and contraindications of st-SCS, operation conditions, and preoperative preparation of st-SCS, and the prospect of the st-SCS procedure. Initially, the survey was conducted on 110 experts who have practiced the st-SCS procedure from all over the provinces in China. Finally, valuable data was calculated from the 110 questionnaires excluding the doctors with <1 year of experience of st-SCS, <10 cases of procedures per year, and no standard training in SCS technique. Results: Based on the 110 questionnaires, it is estimated that 5,000 to 10,000 cases of electrical stimulation are carried out nationwide each year. Sixty-nine valid questionnaires acquired from senior pain physicians were more valuable and specialized in the efficacy, indications, and contraindications of st-SCS for HN. It was commonly agreed (97.10%) that the HN patients with <3 months will obtain good effectiveness (patient satisfaction rate ≥50%). Almost all (98.55%) agreed that st-SCS can be used in SHN patients, there was a common agreement (72.46%) that AHN patients are an indication of st-SCS, and more than half agreement (53.62%) that st-SCS may be fit for early PHN (3-6 months). A common agreement (79.71%) was achieved that more than half of HN patients had the experience of nerve block or nerve pulsed RF. A similarly large number of experts 57/69 (82.61%) agreed that an 80% paresthesia coverage should be achieved at the test stimulation and 57/69 (82.61%) agreed that the treatment of st-SCS need be persistent for 1-2 weeks. Conclusions: Early HN patients can get an effective outcome from the treatment of st-SCS and maybe the indication of st-SCS. Moreover, standardized training for pain physicians and basic research and clinical studies are warranted.

The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury.

Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

Sleep deprivation and recovery sleep affect healthy male resident's pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model.

Sleep is essential for the body's repair and recovery, including supplementation with antioxidants to maintain the balance of the body's redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.

Regulated necrosis in COVID-19: A double-edged sword.

COVID-19 caused by SARS-CoV-2 can cause various systemic diseases such as acute pneumonia with cytokine storm. Constituted of necroptosis, pyroptosis, and ferroptosis, regulated necrosis constitutes the cell death patterns under the low apoptosis condition commonly observed in COVID-19. Regulated necrosis is involved in the release of cytokines like TNF-α, IL-1 ß, and IL-6 and cell contents such as alarmins, PAMPs, and DAMPs, leading to more severe inflammation. Uncontrolled regulated necrosis may explain the poor prognosis and cytokine storm observed in COVID-19. In this review, the pathophysiology and mechanism of regulated necrosis with the double-edged sword effect in COVID-19 are thoroughly discussed in detail. Furthermore, this review also focuses on the biomarkers and potential therapeutic targets of the regulated necrosis pathway in COVID-19, providing practical guidance to judge the severity, prognosis, and clinical treatment of COVID-19 and guiding the development of clinical anti-SARS-CoV-2 drugs.

Comparison of the Efficacy of Short-term Peripheral Nerve Stimulation and Pulsed Radiofrequency for Treating Herpes Zoster Ophthalmicus Neuralgia.

OBJECTIVE: This study aimed to investigate the effect of therapy with peripheral nerve stimulation (PNS) and pulsed radiofrequency (PRF) combined or PNS and PRF separately in patients with herpes zoster ophthalmicus (HZO). MATERIALS AND METHODS: This cohort study included 106 cases of HZO. Three groups were identified according to the type of treatment received: combination therapy (PNS+PRF) (n=38), PRF (n=37), and PNS (n=31). The observations at 0, 1, 2, and 4 weeks; 3 and 6 months; and 1 and 2 years after the operation were analyzed. Observations at each follow-up included baseline characteristics, Numerical Rating Scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI), concomitant pain medication usage, relapse rate, and adverse events. RESULTS: The postoperative NRS of all 3 groups were significantly lower than preoperative scores. The PSQI of the 3 groups was significantly improved postoperatively, and the concomitant pain medication gradually decreased. Regarding long-term efficacy, the pain NRS and PSQI scores of the PNS+PRF and PNS groups were significantly lower than those of the PRF group ( P <0.05), and the relapse rate of the PRF group was higher than that of the PNS+PRF and PNS groups ( P <0.05). No significant difference was observed between the PNS+PRF and the PNS groups. CONCLUSION: Both PNS and PRF treatment of HZO can decrease the pain score, yielding no serious complications. The combination of PNS and PRF or PNS alone resulted in more significant pain relief than treatment with PRF alone. Thus, PNS therapy may be a better treatment option for HZO.

Chinese expert consensus on minimally invasive interventional treatment of trigeminal neuralgia.

Background and purpose: Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application. Materials and methods: The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level. Results: Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia. Conclusions: The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.