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*

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.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective:Empirical analysis of the multiple driving paths of service capabilities of home-and community-based integrated health and social care in China,for providing useful reference for promoting the system improvement.Methods:Based on the World Health Organization's Integrated Care for Older People(ICOPE)implementation framework,an analysis framework for service capabilities of home-and community-based integrated health and social care was constructed.39 districts(counties)in Wuxi,Jiaozuo,Changsha,Chengdu,and Chongqing were included.The fuzzy-set qualitative comparative analysis(fsQCA)method was used to analyze the configuration paths of high or non-high-level service capabilities of home-and community-based integrated health and social care.Results:The service capabilities of home-and community-based integrated health and social care is improved by the configuration of various factors.Four path configurations might contribute to the development of service capabilities of home-and community-based integrated health and social care,and three path configurations might hinder the development.Institutional support,financing mechanism and the demand level of regional aging population are the key factors.Conclusions:Service capabilities of home-and community-based integrated health and social care are affected by the interaction and interrelation between multiple factors.Strategies should be jointly implemented from different aspects to improve service capabilities.

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*

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg