Anti-oxidative stress and cognitive improvement of a semi-synthetic isoorientin-based GSK-3ß inhibitor in rat pheochromocytoma cell PC12 and scopolamine-induced AD model mice via AKT/GSK-3ß/Nrf2 pathway.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive deficits. Although the pathogenesis of AD is unclear, oxidative stress has been implicated to play a dominant role in its development. The flavonoid isoorientin (ISO) and its synthetic derivatives TFGF-18 selectively inhibit glycogen synthase kinase-3ß (GSK-3ß), a potential target of AD treatment. PURPOSE: To investigate the neuroprotective effect of TFGF-18 against oxidative stress via the GSK-3ß pathway in hydrogen peroxide (H2O2)-induced rat pheochromocytoma PC12 cells in vitro and scopolamine (SCOP)-induced AD mice in vivo. METHOD: The oxidative stress of PC12 cells was induced by H2O2 (600 µM) and the effects of TFGF-18 (2 and 8 µM) or ISO (12.5 and 50 µM) were observed. The AD mouse model was induced by SCOP (3 mg/kg), and the effects of TFGF-18 (2 and 8 mg/kg), ISO (50 mg/kg), and donepezil (DNP) (3 mg/kg) were observed. DNP, a currently accepted drug for AD was used as a positive control. The neuronal cell damages were analyzed by flow cytometry, LDH assay, JC-1 assay and Nissl staining. The oxidative stress was evaluated by the detection of MDA, SOD, GPx and ROS. The level of ACh, and the activity of AChE, ChAT were detected by the assay kit. The expressions of Bax, Bcl-2, caspase3, cleaved-caspase3, p-AKT (Thr308), AKT, p-GSK-3ß (Ser9), GSK-3ß, Nrf2, and HO-1, as well as p-CREB (Ser133), CREB, and BDNF were analyzed by western blotting. Morris water maze test was performed to analyze learning and memory ability. RESULTS: TFGF-18 inhibited neuronal damage and the expressions of Bax, caspase3 and cleaved-caspase3, and increased the expression of Bcl-2 in vitro and in vivo. The level of MDA and ROS were decreased while the activities of SOD and GPx were increased by TFGF-18. Moreover, TFGF-18 increased the p-AKT, p-GSK-3ß (Ser9), Nrf2, HO-1, p-CREB, and BDNF expression reduced by H2O2 and SCOP. Meanwhile, MK2206, an AKT inhibitor, reversed the effect of TFGF-18 on the AKT/GSK-3ß pathway. In addition, the cholinergic system (ACh, ChAT, and AChE) disorders were retrained and the learning and memory impairments were prevented by TFGF-18 in SCOP-induced AD mice. CONCLUSIONS: TFGF-18 protects against neuronal cell damage and cognitive impairment by inhibiting oxidative stress via AKT/GSK-3ß/Nrf2 pathway.

Riveting technique in percutaneous balloon compression for trigeminal neuralgia remedy.

BACKGROUND: The percutaneous balloon compression (PBC) is a safe and simple treatment for trigeminal neuralgia. It works by compressing the Gasserian ganglion to block pain signals from the trigeminal nerve. To ensure effectiveness, it is important to focus the compression on the lower part of the balloon. OBJECTIVE: To validate the efficacy of a riveting technique, specifically pulling an inflated balloon, in order to apply enhanced compression on the ganglion. METHODS: To compare this novel technique with the conventional approach, a retrospective investigation was conducted on consecutive PBCs performed in our department between 2019 and 2022. For postoperative outcome assessment, efficacy was defined as achieving a VAS score of 0 or an improvement exceeding 5 points. Postoperative numbness was graded as none, mild, or severe based on its impact on daily life and tolerance level. RESULTS: Excluding cases with missed follow-up, a total of 179 participants were included in the study, and their follow-up period ranged up to 40 months. Postoperatively, symptomatic remission was achieved by 98.1% (52/53) of patients in the riveting technique group compared to 87.3% (110/126) in the conventional group (P<0.05). At the last follow-up period, with recurrence observed over time, the long-term efficacy of riveting and conventional groups were 94.3% and 74.6%, respectively (P<0.05). The majority of cases in both groups experienced ipsilateral facial numbness immediately following PBC, which appeared to diminish after 3 months in both groups without significant difference between them (P>0.05).

Lumbar Endoscopic Unilateral Laminotomy With Bilateral Decompression Surgery in Severe Lumbar Stenosis Under Electrophysiological Monitoring-Focused on Full-Visualized Trephine/Osteotome.

OBJECTIVE: Although endoscopic drill has the advantages in manipulation and hemostasis, whose low efficiency and blurred vision reduce the efficacy of lumbar endoscopic unilateral laminotomy with bilateral decompression (LE-ULBD). The present study was designed to evaluate the safety and efficacy of full-visualized trephine/osteotome in the LE-ULBD surgery for severe lumbar stenosis. METHODS: Fifty-seven severe lumbar stenosis patients who underwent LE-ULBD between January 2020 to January 2023 were enrolled, who were divided into drill and visualized trephine groups. The medical records including demographics, operative duration, intraoperative electrophysiological findings, postoperative hospital stay or hospital stay, postoperative outcomes and complications were retrospectively reviewed and analyzed. RESULTS: A total of 57 patients included 15 in drill and 42 in trephine group were enrolled in the study. There was significant difference in the pre- and postoperative visual analogue scale and Oswestry Disability Index scores in both groups (p < 0.05). The mean operative duration in the trephine group (101.05 ± 12.18 minutes) was shorter than that in the drill group (134.67 ± 9.68 minutes) (p < 0.05). There was no statistical difference between the 2 groups in electrophysiological monitoring, posthospital stays, postoperative outcomes and complications. Abnormal free-electromyography (EMG) were recorded in 2 (13.3%) and 5 patients (11.9%) in the drill and trephine group. Intraoperative somatosensory evoked potential changes occurred in 3 (20%) and 3 patients (7.1%) in the drill and trephine group and all patients recovered immediately when surgery ended. No serious complications and recurrence occurred in all the patients. CONCLUSION: Full-visualized trephine/osteotome has been approved to be convenient, safe and efficient in our study, which combined with translaminar inside-out technique and EMG monitoring especially free-EMG may offer a new choice in LE-ULBD surgery for lumbar stenosis patients.

The Value of a Headless Pear Shape in Percutaneous Balloon Compression for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: Percutaneous balloon compression (PBC) has been regarded as a simple and effective remedy for trigeminal neuralgia. This study aims to retrospectively analyze the correlation between intraoperative balloon shapes and postoperative outcomes. METHOD: Those consecutive PBC cases performed in our department between 2019 and 2022 were reviewed. According to the intraoperative balloon figures, they were cataloged as headless pear, slim pear, bottle gourd, and winter melon groups. The degree of pain or numbness was quantified using the visual analog scale. Those pain-free or pain score <3 and satisfied by the patient were called effective, and those numb score >3 were taken into account of numbness incidence. RESULTS: Except for missing cases, 160 were finally recruited in this study with a mean follow-up for 23.6 ± 12.8 months. Postoperatively, the pain score plunged from 8.8 ± 1.0 to 0.8 ± 2.0 immediately, which rose slightly over time and maintained at 2.4 ± 3.1. The maximal pain score drop occurred in the headless pear group ( P < .001) and the minimal in the winter melon group ( P < .001). The early efficacy of PBC was 100%, 84.1%, 91.4%, and 50.0%, respectively. However, the long-term efficacy was 88.2%, 75.0%, 82.1% and 25.0%. The ipsilateral numbness occurred in most of the cases immediately after PBC with a score of 3.5 ± 2.3, which decreased significantly within 3 months to 2.3 ± 2.0 and turned to 1.7 ± 1.8 finally ( P < .05). The highest and lowest numb score appeared in bottle gourd and winter melon groups, respectively ( P < .05). CONCLUSION: A headless pear shape emerged in lateral fluoroscopy as the balloon was fully inflated indicates that the entire Meckel cave is suffused, and hence, the anterior semilunar ganglion has been solidly compressed, which may lead to a successful outcome.

Ibandronate sodium and zoledronate sodium in the treatment of senile osteoporosis: efficacy, impact on quality of life and cost-effectiveness analysis.

OBJECTIVE: To investigate the efficacy of ibandronate sodium and zoledronate sodium in the treatment of senile osteoporosis and their impact on quality of life, and to analyze the cost-effectiveness. METHODS: A retrospective study was conducted on 215 patients with senile osteoporosis, who were admitted to our hospital from January 2017 to June 2019. Among them, 115 cases treated with ibandronate sodium were set to group A and 100 cases treated with zoledronate sodium were set to group B. The clinical efficacy, bone mineral density (BMD) before and after treatment, bone metabolic markers (alkaline phosphatase (ALP), blood phosphorus (P), blood calcium ion (Ca2+)), quality of life, adverse reactions, cost-effectiveness indicators (length of hospitalization, cost) and complications were compared between the two groups. RESULTS: Total therapeutic response rate in group A was 96.52% (111/115), which was not statistically different from that of 93.00% (93/100) in group B (P=0.242). After treatment, the BMD, ALP, BGP and Ca2+ levels of the lumbar spine L1-L4, left femoral neck and right femoral neck, as well as quality of life scores in the two groups increased (P < 0.05), while serum ALP levels decreased (P < 0.05), however, there was no statistically significant difference between the two groups (P > 0.05). The incidence of adverse reactions in group A was 3.48% (4/115), which showed no statistical significance with that of 5.00% (5/100) in group B (P=0.830). The length of hospitalization, annual treatment expense, medical insurance expense and out-of-pocket payments in group A were all lower than those in group B (P < 0.05). CONCLUSION: In the treatment of senile osteoporosis, the efficacy and adverse reactions of ibandronate sodium and zoledronate sodium are similar, both of them can effectively improve the quality of life. However, the cost-effectiveness of ibandronate sodium is better than that of zoledronate sodium.

Metallothionein-1 is associated with osteoarthritis disease activity and suppresses proinflammatory cytokines production in synovial cells.

BACKGROUNDS: OA (Osteoarthritis) is a predominant degenerative disease, characterized by the synovial inflammation and cartilage destruction. The pathogenic mechanisms remain mostly unknown. There is an critical require for extra investigations to discover new therapeutic targets to prevent and treat OA disease, as there are currently no effective treatments except for the joint replacement. METHODS: The mRNA and protein levels of Metallothionein-1(MT-1) were quantified by qPCR and ELISA in peripheral blood mononuclear cells (PBMCs), serum and synovial cells (SCs) from erosive inflammatory OA (EIOA) and primary generalized OA (PGOA) patients. Age and sex matched healthy volunteers were recruited as healthy controls (HCs). The correlation between the MT-1 level and OA activity was assessed and the anti-inflammatory effects of MT-1 was determined in vitro. RESULTS: The mRNA and protein levels of MT-1 were significantly increased in the PBMCs and serum of EIOA patients compared with those of PGOA patients and HCs. Serum levels of MT-1 were positively correlated with VAS score, CRP, and ESR in OA patients. And the positive correlations were also identified between the MT-1 and IL-1ß, TNF-α or IL-6 in synovial cells. Furthermore, the recombinant MT-1 protein could significantly inhibit the expression of IL-1ß, TNF-α and IL-6 in PBMCs and SCs from EIOA patients in vitro. CONCLUSION: The data had shown that the MT-1 was up-regulated in EIOA patients and positively correlated with the disease activity. The recombinant MT-1 could suppress the expression of pro-inflammatory cytokines in both PBMCs and synovial cells from EIOA patients. Therefore, the MT-1 might become a novel therapeutic target for OA treatment.