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Introduction: The optimal treatment of choledocholithiasis combined with cholecystolithiasis remains controversial. Common surgical methods vary among endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC), laparoscopic transcystic common bile duct exploration (LTCBDE), laparoscopic transductal common bile duct exploration (LCBDE) with or without T-tube drainage. The purpose of this study is to evaluate the safety and effectiveness of surgical methods and to determine the appropriate procedure for patients with cholecystolithiasis combined with choledocholithiasis. Methods: From January 2013 to January 2019, a total of 1555 consecutive patients diagnosed with cholecystolithiasis combined with choledocholithiasis who underwent surgical treatment in Tongji Hospital were retrospectively analyzed. Total 521 patients with intrahepatic bile duct stones underwent LC + LCBDE + T-Tube were excluded from the analysis. At last, 1034 patients who met the inclusion criteria were divided into three groups according to their surgical methods: preoperative ERCP + subsequent LC (ERCP + LC group, n = 275), LC + LCBDE + intraoperative endoscopic nasobiliary drainage (ENBD) + primary duct closure (Tri-scope group, n = 479) and LC + laparoscopic transcystic CBD exploration (LTCBDE group, n = 280). Clinical records, operative findings and postoperative follow-up were collected and analyzed. Results: There was no mortality in three groups. Common bile duct (CBD) stone clearance rate was 97.5% in ERCP + LC group, 98.7% in Tri-scope group, and 99.3% in LTCBDE group. There were no difference in terms of demographic characteristics, biochemistry findings and presentations, but the Tri-scope group had the biggest diameter and amount of stones and diameter of CBD, the LTCBDE group had the least CBD stones and the biggest diameter of cystic gall duct (CGD). ERCP + LC group have the longest hospital stay (14.16 ± 3.88 days vs 6.92 ± 1.71 days vs 10.74 ± 5.30 days, P < 0.05), also has the longest operative time than others (126.08 ± 42.79 min vs 92.31 ± 10.26 min, 99.09 ± 8.46 min, P < 0.05). Compared to ERCP + LC group, LTCBDE group and Tri-scope group had lower postoperation-leukocyte, shorter surgery duration and hospital stay (P < 0.05). Compared to the Tri-scope group, the LTCBDE group had the shorter hospital stay, extubation time and operation time and less intraoperative bleeding. There were less postoperative complications in LTCBDE group (1.1%) compared to the ERCP + LC group (3.6%) and Tri-scope group (2.2%). Follow-up time was 6 to 72 months. Four patients in ERCP + LC group and 5 in Tri-scope group reported recurrent stones. Conclusion: All the three surgical methods are safe and effective. Tri-scope approach and LTCBDE approach have superiority to preoperative ERCP + LC. LC + LTCBDE shows priority over Tri-scope approach, but should be performed in selected patients. LC + LCBDE + T-Tube can be an alternative management if the other three procedures were failed. The surgeons should choose the most appropriate surgical procedure according to the preoperative examination results and intraoperative situation. [ABSTRACT FROM AUTHOR]

Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia–reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia–reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.  [ABSTRACT FROM AUTHOR]

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH. [ABSTRACT FROM AUTHOR]