Efficacy and Safety of Different Preemptive Analgesia Measures in Pain Management after Laparoscopic Cholecystectomy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The purpose of this systematic review and network meta-analysis was to evaluate the efficacy and safety of different preemptive analgesia measures given before laparoscopic cholecystectomy (LC) for postoperative pain in patients. METHODS: We conducted a comprehensive search in databases including PubMed, Web of Science, Embase, and the Cochrane Library up to March 2024, and collected relevant research data on the 26 preemptive analgesia measures defined in this article in LC surgery. Outcomes included postoperative Visual Analogue Scores (VAS) at different times (2, 6, 12, and 24 h), opioid consumption within 24 h post-operation, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), and incidence of postoperative headache or dizziness. RESULTS: Forty-nine articles involving 5987 patients were included. The network meta-analysis revealed that multimodal analgesia, nerve blocks, pregabalin, and gabapentin significantly reduced postoperative pain scores at all postoperative time points and postoperative opioid consumption compared to placebo. Tramadol, pregabalin, and gabapentin significantly extended the time to first rescue analgesia. Ibuprofen was the best intervention for reducing PONV incidence. Tramadol significantly reduced the incidence of postoperative headache or dizziness. Subgroup analysis of different doses of pregabalin and gabapentin showed that compared to placebo, pregabalin (300 mg, 150 mg) and gabapentin (600 mg, 300 mg, and 20 mg/kg) were all more effective without significant differences in efficacy between these doses. Higher doses increased the incidence of PONV and postoperative headache and dizziness, with gabapentin 300 mg having a lower adverse drug reaction (ADR) incidence. CONCLUSIONS: Preemptive analgesia significantly reduced postoperative pain intensity, opioid consumption, extended the time to first rescue analgesia, and decreased the incidence of PONV and postoperative headache and dizziness. Multimodal analgesia, nerve blocks, pregabalin, and gabapentin all showed good efficacy. Gabapentin 300 mg given preoperatively significantly reduced postoperative pain and ADR incidence, recommended for preemptive analgesia in LC. TRIAL REGISTRATION: PROSPERO CRD42024522185.

Association of Interleukin-6 Polymorphisms with Schizophrenia and Depression: A Case-Control Study.

OBJECTIVE: Growing evidence suggests a crossover in genetic susceptibility to schizophrenia and depression. We aimed to investigate the association of the rs1800795 and rs1800796 polymorphisms of the IL-6 gene with schizophrenia and depression in the Han Chinese population, combined with IL-6 serum levels. METHODS: Gene sequencing and enzyme-linked immunosorbent assay were performed on 113 subjects with schizophrenia, 114 subjects with depression, and 110 healthy controls. RESULTS: Our findings showed that IL-6 concentrations in schizophrenia and depression groups were significantly higher than in the control group. The rs1800796 CC genotype and C allele were significantly associated with depression (P = .012 and P < .05, respectively). The rs1800796 CC and CG genotype was significantly associated with chronic schizophrenia (P = .020 and P = .009, respectively). Regarding the rs1800795 polymorphism, only one case of CG genotype was detected. The remainder were of the GG genotype. CONCLUSION: The IL-6 rs1800796 might serve as a protective factor for depression and schizophrenia in the Han Chinese population.

Regulation of survivin and caspase/Bcl-2/Cyto-C signaling by TDB-6 induces apoptosis of colorectal carcinoma LoVo cells.

Background: Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism. Methods: The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo. Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells. Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/Cyto-C signaling. Results: The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo. Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2. Conclusions: TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment.