Efficacy and Safety of Computed Tomography-Guided Percutaneous Balloon Compression under Local Anesthesia for Recurrent Trigeminal Neuralgia: A Prospective Study.

Purpose: There are several ways to treat trigeminal neuralgia (TN); however, TN may recur after treatment. This study investigated the efficacy and safety of computed tomography (CT)-guided percutaneous balloon compression (PBC) under local anesthesia for treatment of recurrent trigeminal neuralgia. Patients and Methods. This is a prospective and nonrandomized controlled clinical study. Forty-eight patients with classical TN were scheduled to undergo PBC surgery at the pain department of our institution between January 2021 and June 2021. The patients were prospectively divided into an initial onset group, A (21 cases), and a recurrence group, B (27 cases). All surgeries were performed with CT guidance and under local anesthesia. Postoperative complications were also observed. Pain was assessed using the visual analog scale (VAS) and Barrow Neurological Institute (BNI) scale. Efficacy indices were evaluated at 3, 6, 12, and 18 months after surgery. Results: All participants reported complete pain relief at discharge. After 18 months of follow-up, the total effective rate of pain control was 89.5% (group A, 90.5%; group B, 88.8%). There was no significant difference in the BNI scores between the two groups before and after treatment. All patients had hypoesthesia on the affected side, and no severe complications such as diplopia, blindness, intracranial hemorrhage, or intracranial infection occurred. Conclusions: CT-guided PBC under local anesthesia is safe and effective for the treatment of recurrent TN and thus acts as an effective alternative for geriatric patients and those with high-risk factors.

Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe.

S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.

In Situ Fluorescence Imaging Reveals Contribution of Cerebral Hydroxyl Radicals in Hyperhomocysteinemia-Induced Alzheimer-like Dementia.

Elevated plasma level of homocysteine, also termed as hyperhomocysteinemia, is acknowledged as a significant and independent risk factor of Alzheimer's disease. However, the mechanistic insight has not been thoroughly elucidated yet. In this work, 3,5-dihydroxybenzyloxy was explored as the unique reaction trigger and integrated into the naphthalimide fluorophore via a carbamate linker to afford a new probe for •OH imaging. •OH treatment induced aromatic hydroxylation and subsequent elimination reaction to release the caged fluorophore, accompanied with a highly specific and sensitive turn-on fluorescence response. Cell imaging results revealed that excess homocysteine triggered overwhelming •OH production, which was mediated by N-methyl-d-aspartate receptor and NADPH oxidase, and the resultant •OH stress further initiated neuronal ferroptosis, also confirmed by western blot analyses. Additionally, hyperhomocysteinemic mouse models were established, and Alzheimer-like dementia of the mice was observed from behavioral tests. Most importantly, with this probe, cerebral •OH fluctuation was in situ visualized in live mice, which positively correlated with the severity of Alzheimer-like dementia induced by hyperhomocysteinemia. These results reveal that cerebral •OH stress may be the critical nexus linking hyperhomocysteinemia and Alzheimer's disease. This work provides a robust fluorescence probe for in situ visualizing the cerebral •OH fluctuations and illuminating critical insights into •OH contributions in brain disorders.

Comparative safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression in CT-guided and local anesthesia for recurrent trigeminal neuralgia.

Background: There are several ways to treat trigeminal neuralgia (TN); however, TN may recur after treatment. Although microvascular decompression (MVD) is considered an effective treatment for trigeminal neuralgia, patients with recurrence may not be willing to undergo craniotomy. Objective: This study compared the safety and efficacy of percutaneous radiofrequency thermocoagulation and percutaneous balloon compression for treating recurrent trigeminal neuralgia. Methods: This was a prospective non-randomized controlled study. A total of 52 with recurrent TN were scheduled to undergo surgery in our Hospital from January-June 2021. The patients were classified into percutaneous radiofrequency thermocoagulation (PRT) and percutaneous balloon compression (PBC) groups based on the treatment. All surgeries were performed under computed tomography guidance and local anesthesia. Post-operative complications were also observed. Pain was assessed using the visual analog scale (VAS) and Barrow Neurological Institute (BNI) scale. Efficacy indices were evaluated at 3, 6, 12, and 18 months after surgery. Results: During follow-up, the efficacy rates of the two methods within 18 months were 76.0 and 88.9%, respectively. All patients had hypoesthesia on the affected side, and no severe complications. Notably, 5 patients (20%) in the PRT group with multiple-branch pain, including the first branch of the trigeminal nerve (V1) pain in the PRT group, received radiofrequency therapy for the supraorbital notch (foramen) after puncture of the foramen ovale. However, multiple pain episodes resolved with only one operation in the PBC group. Conclusion: CT-guided percutaneous radiofrequency thermocoagulation and percutaneous balloon compression under local anesthesia may be good options for treating recurrent trigeminal neuralgia. Percutaneous balloon compression may be recommended when multiple branches are involved, particularly in cases of V1 neuralgia.

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.

Photocontrollable Fluorescence Imaging of Mitochondrial Peroxynitrite during Ferroptosis with High Fidelity.

Ferroptosis, a new regulatory cell death modality, underlies the pathogenesis of a broad range of disorders. Although much efforts have been made to uncover the molecular mechanisms, some mechanistic details of ferroptosis still remain poorly understood. Particularly, the functional relevance of mitochondrial reactive oxygen species (ROS) in ferroptosis is still highly controversial, which is partially due to the fact that it still remains puzzled how the mitochondrial ROS level varies during ferroptosis. The conventional mitochondria-targeted probes may react with cytosolic ROS and show fluorescence variation before entering mitochondria, thus probably giving a false result on the mitochondrial ROS level and leading to the misjudgment on its biofunction. To circumvent this issue, we rationally designed a photocontrollable and mitochondria-targeted fluorescent probe to in situ visualize the mitochondrial peroxynitrite (ONOO-), which is the ROS member and mediator of ferroptosis. The photoactivated probe was endowed with a highly specific and sensitive fluorescence response to ONOO-. Notably, the response activity could be artificially regulated with light irradiation, which ensured that all the probe molecules passed through the cytosol in the locked status and were then photoactivated after reaching mitochondria. This photocontrolled fluorescence imaging strategy eliminated the interference of ONOO- outside the mitochondria, thus potentially afforded improved fidelity for mitochondrial ONOO- bioimaging in live cells and animal models. With this probe, for the first time, we revealed the mitochondrial ONOO- flux and its probable biological source during erastin-induced ferroptosis. These results suggest a tight correlation between mitochondrial ONOO-/ROS and ferroptotic progression, which will further facilitate the comprehensive exploration and manipulation of ferroptosis.

Two-photon fluorescence imaging of the cerebral peroxynitrite stress in Alzheimer's disease.

We designed and synthesized an oxindole-functionalized two-photon fluorescent probe based on a naphthalimide fluorophore, which enabled in situ visualization of the overwhelming peroxynitrite flux during amyloid-ß-induced neuronal ferroptosis and cerebral peroxynitrite stress in live mice with Alzheimer's disease.

Dual-Channel Imaging of Amyloid-ß Plaques and Peroxynitrite To Illuminate Their Correlations in Alzheimer's Disease Using a Unimolecular Two-Photon Fluorescent Probe.

Alzheimer's disease (AD) involves multiple pathological factors that mutually cooperate and closely contact to form interaction networks for jointly promoting the AD progression. Therefore, the comonitoring of different factors is particularly valuable for elucidating their level dynamics and complex interactions. However, such significant investigations remain a major challenge due to the lack of unimolecular fluorescent probes capable of simultaneous and discriminative visualization of multiple targets. To address this concern, as proof of principle, we rationally designed a unimolecular fluorescent probe to discriminate and simultaneously profile amyloid-ß (Aß) plaques and peroxynitrite (ONOO-), which are both the pronounced AD pathological factors. Herein, a novel ONOO- reaction trigger was installed onto an Aß plaque binding fluorophore to generate a dual functional fluorescent probe, displaying completely separate spectral responses to Aß plaques and ONOO- with high selectivity and sensitivity. With this probe, for the first time, we comonitored the distribution and variation of Aß plaques and ONOO- through two independent fluorescence channels, demonstrating their close apposition and tight correlation during AD course in live cell and mouse models through two-photon imaging mode. Notably, Aß aggregates induce the neuronal ONOO- generation, which conversely facilitates Aß aggregation. The two critical events, ONOO- stress and Aß aggregation, mutually amplify each other through positive feedback mechanisms and jointly promote the AD onset and progression. Furthermore, by coimaging of the level dynamics of Aß plaques and ONOO-, we found that the cerebral ONOO- is a potential biomarker, which emerges earlier than Aß plaques in transgenic mouse models. Overall, the dual-channel responsive performance renders this probe as a powerful imaging tool to decipher Aß plaque-ONOO- interactions, which will facilitate AD-associated molecular pathogenesis elucidation and multitarget drug discovery.

Expert consensus of Chinese Association for the Study of Pain on the application of ozone therapy in pain medicine.

This consensus was compiled by first-line clinical experts in the field of pain medicine and was organized by the Chinese Association for the Study of Pain. To reach this consensus, we consulted a wide range of opinions and conducted in-depth discussions on the mechanism, indications, contraindications, operational specifications and adverse reactions of ozone iatrotechnique in the treatment of pain disorders. We also referred to related previous preclinical and clinical studies published in recent years worldwide. The purpose of this consensus is to standardize the rational application of ozone iatrotechnique in pain treatment, to improve its efficacy and safety and to reduce and prevent adverse reactions and complications in this process.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain.

Chronic musculoskeletal pain (CMP) is a common occurrence in clinical practice and there are a variety of options for the treatment of it. However, the pharmacological therapy is still considered to be a primary treatment. The recent years have witnessed the emergence of opioid crisis, yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly. The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics. The purpose of this consensus is to present the application of nonsteroidal anti-inflammatory drugs, serotonin norepinephrine reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, muscle relaxants, ion channel drugs and topical drugs in CMP.

Expert consensus of the Chinese Association for the Study of Pain on ion channel drugs for neuropathic pain.

Neuropathic pain (NPP) is a kind of pain caused by disease or damage impacting the somatosensory system. Ion channel drugs are the main treatment for NPP; however, their irregular usage leads to unsatisfactory pain relief. To regulate the treatment of NPP with ion channel drugs in clinical practice, the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs . Here, we reviewed the mechanism and characteristics of sodium and calcium channel drugs, and developed recommendations for the therapeutic principles and clinical practice for carbamazepine, oxcarbazepine, lidocaine, bulleyaconitine A, pregabalin, and gabapentin. We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.

Effects of Continuous Epidural Injection of Dexamethasone on Blood Glucose, Blood Lipids, Plasma Cortisol and ACTH in Patients With Neuropathic Pain.

Objective: To study the effects of continuous epidural injection of dexamethasone on blood glucose, blood lipids, plasma cortisol, and adrenocorticotropic hormone (ACTH) in patients with neuropathic pain. Methods: Thirty patients with cervical spondylotic radiculopathy, lumbar disc herniation, herpes pain or postherpetic neuralgia were randomly divided into three groups and were treated with different doses of epidural injection of dexamethasone (Group S with a concentration of 25 µg/mL; Group M with a concentration of 50 µg/mL; Group L with a concentration of 100 µg/mL). Epidural catheterization placement was guided by computed tomography (CT), and was connected to the analgesic pump for 10 days. Visual Analog Score (VAS), fasting blood glucose (FBG), total cholesterol (CHOL), triglyceride (TG), 2 h postprandial blood glucose (2hPG) and the concentrations of cortisol, ACTH were measured before injection (T0), 2, 4, 6, 8, and 10 days during injection (D2, D4, D6, D8, D10), and 7, 14, 21, 28 days (W1, W2, W3, W4) after injection. Results: During and after the treatment, VAS score was significantly decreased, and group M and L had the lowest VAS score. The concentrations of cortisol and ACTH were significantly lower during the treatment, but all of them recovered to the normal level after stopping the injection. The treatment did not affect the CHOL and TG concentrations. Discussion: Epidural injection of dexamethasone at the concentration of 50 µg/mL is recommended for patients with neuropathic pain because of its good analgesic effect and less adverse effect on blood glucose, plasma cortisol, and ACTH.

A Facile, Versatile, and Highly Efficient Strategy for Peroxynitrite Bioimaging Enabled by Formamide Deformylation.

Peroxynitrite (ONOO-) is attracting increasing attention due to its involvement in multiple facets of pathophysiological processes. However, ONOO- bioimaging is still challenging due to (1) the lack of highly specific reaction triggers, (2) the tedious and low-yielding synthesis of current sophisticated probes, and (3) the lack of availability of a versatile chemical strategy. To address these challenges, on the basis of amine formylation/deformylation chemistry, we have developed a novel strategy for ONOO- bioimaging. As proof of principle, we designed, synthesized, and evaluated four novel fluorescent probes equipped with the formamide functionality. Although they feature distinctly different fluorophore classes, all probes can be synthesized in one step in high yields and exhibit particularly specific, highly sensitive, and rapid responses to ONOO-. The bioimaging capability is well demonstrated by successfully visualizing ONOO- fluctuation in live cells and major organs of mice suffering from paraquat poisoning. The proposed strategy has proved to be a facile, versatile, and highly efficient methodology for ONOO- visualization, which will greatly facilitate ONOO- biochemistry and pathophysiology.

Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as Visualized by a Two-Photon Near-Infrared Fluorescent Probe.

Anthracyclines rank among the most efficacious anticancer medications. However, their clinical utility and oncologic efficacy are severely compromised by the cardiotoxicity risk facing the early-diagnosis difficulty and their unclear molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary specificity and sensitivity and a rapid response toward peroxynitrite (ONOO-), as well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate that mitochondrial ONOO- is upregulated in the early stage and contributes to the onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse models; therefore, it represents an early biomarker to predict subclinical cardiotoxicity induced by drug challenge. Furthermore, TPNIR-FP is proved to be a robust imaging tool to provide critical insights into drug-induced cardiotoxicity and other ONOO--related pathophysiological processes.

Efficacy and Safety of Repeated Percutaneous Radiofrequency Thermocoagulation for Recurrent Trigeminal Neuralgia.

Background: Percutaneous radiofrequency thermocoagulation (PRT) is used to treat trigeminal neuralgia (TN) with a satisfactory pain relief but a high recurrence rate. Objective: To explore the efficacy and safety of repeated PRT for recurrent TN as compared to patients who received the first PRT. Methods: Between January 2013 to May 2013, 31 patients with recurrent TN who have been treated with PRT previously were recruited and underwent repeated PRT (group A), and compared with 41 TN patients received the first initial PRT (group B). Visual Analog Scale (VAS) score was assessed preoperatively and postoperatively after 2 years of follow-up, and compared in terms of initial pain relief, complications, and recurrence rate between the two groups. Results: In group A, 27 patients (87.0%) were pain free immediately, and 30 patients (96.8%) experienced pain relief at 48 h, whereas that was 37 patients (90.0%) and 40 patients (97.6%) in group B (p ≧ 0.05). Patients in group A who remained an "excellent" or "good" pain relief condition (VAS score ≦ 1) were 96.8% at 6 months, 83.9% at 1 year, 74.2% at 2 years, whereas the percentage in group B was 97.6, 85.4, and 73.2% (p ≧ 0.05). Conclusion: For patients with recurrent TN after PRT, repeated PRT might be considered as a useful treatment option when other treatments fail. In addition, the frequency and severity of adverse events for repeated PRT were similar as compared to initial PRT.

RGD and polyhistidine tumor homing peptides potentiates the action of human Maspin as an antineoplastic candidate.

Maspin, a non-inhibitory member of serine protease family, acts as an effective tumor suppressor by inhibiting cell inhesion and mobility. We found that exogenous wild-type rMaspin had a low effect on tumor growth in vivo. However, when the peptide Arg-Gly-Asp-hexahistidine (RGD-6His) was introduced into rMaspin, the modified rMaspin showed significant inhibitory activity in angiogenic assays and tumor-bearing animal models. Overall, our data suggested that both the RGD and hexahistidine fragments contributed to improve the fusion protein activity and polyhistidine peptide could be considered as flexible linker to separate RGD and Maspin moieties to avoid function interference. Besides, it is an efficient tag to achieve purified recombinant proteins. Furthermore, rMaspin fusing with RGD and hexahistidine could be a viable anticancer candidate.