Objective To analyse the clinical efficiency of endolymphatic sac surgery (ESS) in the management of Meniere’s disease (MD). Methods A retrospective analysis was conducted on 274 patients with MD who were hospitalized for treatment in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University from January 2009 to August 2023. All patients received lifestyle management and drug treatment such as diuretics. For those whose conditions were not well controlled 3 to 6 months after the initial treatment, intratympanic glucocorticoid (ITG) or ESS treatment was carried out. Six months after the treatment, the classes of vertigo relief and hearing changes in the patients were evaluated. After adjusting the confounding factors through propensity score matching (PSM), the impact of ESS on the prognosis of MD patients was evaluated. Results Among 274 patients, 194 and 80 patients underwent ITG and ESS, respectively. Eighty patients were enrolled into each group after PSM. Before and after PSM, the rate of patients reaching vertigo relief class A in ESS group was higher than that in the ITG group (P＝0.004); there was no significant difference in hearing preservation between the two groups. Kaplan-Meier curve analysis showed that vertigo relief in the ESS group was better than that in the ITG group (P=0.029); there was no statistically significant difference in hearing preservation between the two groups. Conclusion When the initial treatment for patients with MD is ineffective, choosing ESS is more beneficial than ITG for controlling vertigo.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

Objective:To analyze the predictive value of the prognostic nutritional index combined with inflammatory indicators for clinical outcomes in patients with ischemic stroke, providing a basis for targeted therapeutic interventions and nursing care for patients at potential risk of poor outcomes.Methods:This retrospective cohort study recruited 424 ischemic stroke patients admitted to the Stroke Center of the First Hospital of Jilin University from June 2021 to May 2024 by the convenience sampling method. Collect the general demographic data, routine laboratory examination results within 24 hours of admission, as well as the National Institutes of Health Stroke Scale (NIHSS) scores at admission and discharge of the patients. Based on 3-month functional outcomes, patients were divided into a favorable prognosis group and a poor prognosis group. Univariate analysis, least absolute shrinkage and selection operator regression, and binary Logistic regression were employed to screen predictive variables and develop a nomogram model. Internal validation was performed using the Bootstrap method. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drew to evaluate the predictive performance of the model.Results:The favorable prognosis group comprised 256 patients, including 57 females and 199 males, with an age of 61(54, 68) years. The poor prognosis group included 168 patients, with 55 females and 113 males, and an age of 66(58, 72) years. Binary Logistic regression identified age, sex, hyperlipidemia, NIHSS score at discharge, prognostic nutritional index, systemic inflammatory response index, and systemic immune-inflammation index as independent predictors of prognosis in ischemic stroke patients ( χ2 values were 4.52-56.18, all P<0.05). The prediction model demonstrated the area under the curve of ROC of 0.806 (95% CI 0.764-0.849), with an optimal cutoff value of 0.406, achieving specificity of 78% and sensitivity of 68%. The Hosmer-Lemeshow test yielded a non-significant P>0.05, and the calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.012. Decision curve analysis confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions:The integrated prognostic model combining the prognostic nutritional index and inflammatory indicators demonstrated favorable discriminative ability, robust calibration, and substantial clinical utility. This risk stratification tool shows high applicability for predicting ischemic stroke outcomes, facilitating early identification of high-risk patients with poor prognosis and guiding personalized intervention strategies.

Objective:To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS).Methods:This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute′s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0.Results:From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event.Conclusion:Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

Objective:To analyze the predictive value of the prognostic nutritional index combined with inflammatory indicators for clinical outcomes in patients with ischemic stroke, providing a basis for targeted therapeutic interventions and nursing care for patients at potential risk of poor outcomes.Methods:This retrospective cohort study recruited 424 ischemic stroke patients admitted to the Stroke Center of the First Hospital of Jilin University from June 2021 to May 2024 by the convenience sampling method. Collect the general demographic data, routine laboratory examination results within 24 hours of admission, as well as the National Institutes of Health Stroke Scale (NIHSS) scores at admission and discharge of the patients. Based on 3-month functional outcomes, patients were divided into a favorable prognosis group and a poor prognosis group. Univariate analysis, least absolute shrinkage and selection operator regression, and binary Logistic regression were employed to screen predictive variables and develop a nomogram model. Internal validation was performed using the Bootstrap method. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drew to evaluate the predictive performance of the model.Results:The favorable prognosis group comprised 256 patients, including 57 females and 199 males, with an age of 61(54, 68) years. The poor prognosis group included 168 patients, with 55 females and 113 males, and an age of 66(58, 72) years. Binary Logistic regression identified age, sex, hyperlipidemia, NIHSS score at discharge, prognostic nutritional index, systemic inflammatory response index, and systemic immune-inflammation index as independent predictors of prognosis in ischemic stroke patients ( χ2 values were 4.52-56.18, all P<0.05). The prediction model demonstrated the area under the curve of ROC of 0.806 (95% CI 0.764-0.849), with an optimal cutoff value of 0.406, achieving specificity of 78% and sensitivity of 68%. The Hosmer-Lemeshow test yielded a non-significant P>0.05, and the calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.012. Decision curve analysis confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions:The integrated prognostic model combining the prognostic nutritional index and inflammatory indicators demonstrated favorable discriminative ability, robust calibration, and substantial clinical utility. This risk stratification tool shows high applicability for predicting ischemic stroke outcomes, facilitating early identification of high-risk patients with poor prognosis and guiding personalized intervention strategies.

OBJECTIVE: To evaluate the feasibility, safety, and early effectiveness of percutaneous endoscopic thoracic spine surgery via the trench technique for ventral decompression in central calcified thoracic disc herniation (CCTDH) and thoracic ossification of the posterior longitudinal ligament (T-OPLL). METHODS: Seven patients with single-segment CCTDH or T-OPLL admitted between June 2017 and May 2020 and meeting the selection criteria were retrospectively analyzed. There were 3 males and 4 females with an average age of 51.7 years ranging from 41 to 62 years. There were 2 patients with T-OPLL (T _{1, 2} in 2 cases) and 5 patients with CCTDH (T _{1, 2} in 1 case, T _{7, 8} in 1 case, T _{10, 11} in 2 cases, T _{11, 12} in 1 case). Five patients with thoracic axial pain and intercostal neuralgia had a preoperative visual analogue scale (VAS) score of 6.0 (5.0, 6.5), and 7 patients had a preoperative Japanese Orthopaedic Association (JOA) score of 21 (21.0, 22.0). Transforaminal approach was used in 4 cases and transpedicular approach in 3 cases. Ventral decompression of thoracic spinal cord was performed by thoracic endoscopy combined with trench technique. The operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications were recorded. Thoracic spine CT and MRI were performed preoperatively and postoperatively to evaluate the surgical decompression, VAS score was used to evaluate the pain of thoracic back and lower limbs, and JOA score was used to evaluate the functional recovery. Modified MacNab criteria was used to evaluate the effectiveness. RESULTS: All surgeries were successfully completed. The operation time ranged from 60 to 100 minutes, with an average of 80.4 minutes; the intraoperative blood loss ranged from 40 to 75 mL, with an average of 57.1 mL; the postoperative hospital stay ranged from 4 to 7 days, with an average of 5.4 days. CT and MRI examinations indicated that the decompression was adequate. All 7 patients were followed up 3-22 months, with an average of 13.3 months. One case developed postoperative wound infection, and 1 case developed pneumonia; the remaining patients did not have any complications such as wound infection or cerebrospinal fluid leakage. Five patients with thoracic axial pain and intercostal neuralgia had VAS scores of 2.0 (1.5, 2.5) at 1 day after operation and 2.0 (1.0, 2.0) at last follow-up, both of which were significantly lower than the preoperative scores ( P<0.05). At 1 day after operation, the JOA scores for all 7 patients were 22.0 (21.0, 24.0), which showed no significant difference compared to the preoperative score ( P>0.05); however, at last follow-up, the score improved to 24.0 (24.0, 26.0), which was significant compared to the preoperative scores ( P<0.05). At last follow-up, the effectiveness was assessed using the modified MacNab criteria, the results were excellent in 2 cases, good in 3 cases, fair in 2 cases, and the excellent and good rate was 71.4%. CONCLUSION Using the trench technique, percutaneous endoscopic thoracic spine surgery can achieve the ventral decompression in CCTDH and T-OPLL, providing a new approach for surgical treatment of CCTDH and T-OPLL.
Humans ; Middle Aged ; Male ; Female ; Thoracic Vertebrae/surgery* ; Decompression, Surgical/methods* ; Adult ; Intervertebral Disc Displacement/surgery* ; Spinal Cord Compression/etiology* ; Treatment Outcome ; Ossification of Posterior Longitudinal Ligament/surgery* ; Endoscopy/methods*

Separation and determination of chiral and achiral impurities in glimepiride tablets by supercritical fluid chromatography. Chiral and achiral impurities were separated on a ACQUITY UPC² Trefoil^TM CEL1 column (150 mm × 3.0 mm, 2.5 μm) maintained at 30 ℃ with the mobile phase containing a mixture of CO₂ and methanol-isopropanol (1∶1) at 1 mL·min^-1, and the detection wavelength was set at 228 nm. The back pressure was set at 13.8 MPa. The injection volume was 5 μL. In the chromatogram of the system suitability solution, the peaks elute in the following order: impurity Ⅳ, impurity Ⅴ, glimepiride, impurity Ⅲ, impurity Ⅰ and impurity Ⅱ. The six substances were separated successfully in 6 min using the proposed method with a resolution factor of 2.9, 1.6, 3.0, 2.0, 6.4. The impurity Ⅰ-Ⅴ detection limit (S/N = 3) was 0.17, 0.10, 0.06, 0.15, 0.10 μg·mL^-1, respectively. Good linear relationship was established between the peak response and the concentration in the range of 0.48-51.30 μg·mL^-1 for all impurities. The spiked recovery of impurity Ⅰ-Ⅴ was found to be acceptable for 99.9%, 98.9%, 102.1%, 100.1%, 96.3% (n = 9), respectively. The related substance and assay results of 11 sample batches are consistent with the results obtained using the HPLC method in the Chinese Pharmacopoeia. Compared to the two HPLC methods in the Chinese Pharmacopoeia, the established supercritical fluid chromatography method can simultaneously separate glimepiride and its 5 impurities in a single run, and it has the following advantages: simplified sample preparation, greatly reducing the volumes of organic solvents, environmentally friendly, high accuracy and good reproducibility. It can be employed for the quality control of the chiral and achiral impurities in glimepiride tablets.