Comparative study of Indocyanine Green fluorescence imaging versus conventional fiber-optic imaging in laparoscopic choledochotomy for stone extraction and immediate biliary incision suturing.

To explore the Advantages of Indocyanine Green (ICG) Fluorescence Imaging over Conventional Fiber-Optic Imaging in Laparoscopic Cholangiography and Immediate Suture for Stone Removal. The study is a randomized controlled descriptive research. Consecutive patient data were collected from October 2022 to January 2024 at the Second People's Hospital of Chengdu for those who underwent laparoscopic bile duct exploration and stone removal, totaling 72 cases. According to the order of admission, they were randomly assigned to either the study group or the control group, with 36 cases in each group. Ten minutes preoperatively, indocyanine green (ICG) was administered intravenously through a peripheral vein to the subjects in the study group, to enable real-time fluorescent tracing of the extrahepatic bile ducts during surgery. This study compares the efficiency of bile duct structure and boundary recognition, the timeliness of bile duct incision positioning, operative time, blood loss, and the incidence of bile duct injury between patients who were injected with ICG and those who were not. In addition, it assesses liver function and white blood-cell counts rechecked 24 h postoperatively, the duration of postoperative hospital stay, and the occurrence of bile leakage. The study included 72 patients, with 36 in the indocyanine green (ICG) fluorescence group and 36 in the conventional fiber-optic group, comprising 26 males and 46 females. There were 18 patients with a history of previous biliary exploration surgery and 23 who had undergone previous cholecystectomy. During surgery, ICG fluorescence was successfully visualized in all 36 cases of the ICG group, allowing for a clear view of the anatomical structure and boundaries of the extrahepatic bile ducts. Compared to the control group, the ICG fluorescence group demonstrated a reduction in the time required for identification of the biliary system and positioning of the bile duct incision, as well as a decrease in operative time and postoperative hospital stay; intraoperative blood loss and the incidence of bile leakage were also relatively reduced, with statistically significant differences (P < 0.05). However, there were no statistically significant differences in postoperative serum alanine aminotransferase levels, white blood-cell counts, direct bilirubin, and indirect bilirubin between the two groups (P > 0.05). One case of bile duct injury occurred in the control group. The application of ICG fluorescence navigation in laparoscopic cholecystectomy can effectively enhance the visibility of the bile ducts, rapidly identify the location for bile duct incision, and is conducive to reducing both the duration of surgery and postoperative hospital stay. It also minimizes intraoperative blood loss, prevents bile leakage and bile duct injuries. This program has demonstrating significant clinical value.

AMPK role in epilepsy: a promising therapeutic target?

Epilepsy is a complex and multifaceted neurological disorder characterized by spontaneous and recurring seizures. It poses significant therapeutic challenges due to its diverse etiology and often-refractory nature. This comprehensive review highlights the pivotal role of AMP-activated protein kinase (AMPK), a key metabolic regulator involved in cellular energy homeostasis, which may be a promising therapeutic target for epilepsy. Current therapeutic strategies such as antiseizure medication (ASMs) can alleviate seizures (up to 70%). However, 30% of epileptic patients may develop refractory epilepsy. Due to the complicated nature of refractory epilepsy, other treatment options such as ketogenic dieting, adjunctive therapy, and in limited cases, surgical interventions are employed. These therapy options are only suitable for a select group of patients and have limitations of their own. Current treatment options for epilepsy need to be improved. Emerging evidence underscores a potential association between impaired AMPK functionality in the brain and the onset of epilepsy, prompting an in-depth examination of AMPK's influence on neural excitability and ion channel regulation, both critical factors implicated in epileptic seizures. AMPK activation through agents such as metformin has shown promising antiepileptic effects in various preclinical and clinical settings. These effects are primarily mediated through the inhibition of the mTOR signaling pathway, activation of the AMPK-PI3K-c-Jun pathway, and stimulation of the PGC-1α pathway. Despite the potential of AMPK-targeted therapies, several aspects warrant further exploration, including the detailed mechanisms of AMPK's role in different brain regions, the impact of AMPK under various conditional circumstances such as neural injury and zinc toxicity, the long-term safety and efficacy of chronic metformin use in epilepsy treatment, and the potential benefits of combination therapy involving AMPK activators. Moreover, the efficacy of AMPK activators in refractory epilepsy remains an open question. This review sets the stage for further research with the aim of enhancing our understanding of the role of AMPK in epilepsy, potentially leading to the development of more effective, AMPK-targeted therapeutic strategies for this challenging and debilitating disorder.

Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.

Diabetic patients receiving the antidiabetic drug metformin have been observed to exhibit a lower prevalence of anxiety disorders, yet the precise mechanism behind this phenomenon is unclear. In our study, we found that anxiety induces a region-specific reduction in AMPK activity in the medial prefrontal cortex (mPFC). Concurrently, transgenic mice with brain-specific AMPK knockout displayed abnormal anxiety-like behaviors. Treatment with metformin or the overexpression of AMPK restored normal AMPK activity in the mPFC and mitigated social stress-induced anxiety-like behaviors. Furthermore, the specific genetic deletion of AMPK in the mPFC not only instigated anxiety in mice but also nullified the anxiolytic effects of metformin. Brain slice recordings revealed that GABAergic excitation and the resulting inhibitory inputs to mPFC pyramidal neurons were selectively diminished in stressed mice. This reduction led to an excitation-inhibition imbalance, which was effectively reversed by metformin treatment or AMPK overexpression. Moreover, the genetic deletion of AMPK in the mPFC resulted in a similar defect in GABAergic inhibitory transmission and a consequent hypo-inhibition of mPFC pyramidal neurons. We also generated a mouse model with AMPK knockout specific to GABAergic neurons. The anxiety-like behaviors in this transgenic mouse demonstrated the unique role of AMPK in the GABAergic system in relation to anxiety. Therefore, our findings suggest that the activation of AMPK in mPFC inhibitory neurons underlies the anxiolytic effects of metformin, highlighting the potential of this primary antidiabetic drug as a therapeutic option for treating anxiety disorders.