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The study aimed to explore whether cancer-related pain and opioids use are associated with the survival of cancer patients, and perform a cohort study and a meta-analysis to quantify the magnitude of any association. A retrospective cohort study was performed to analyze the impact of pain level, and opioids use on cancer-specific survival (CSS) in advanced cancer patients. Patients and relevant medical records were selected from the registry of the Radiation and chemotherapy division of Ningbo First Hospital between June 2013 and October 2017. Hazard ratios (HRs) and 95% confidential intervals (CIs) for CSS by opioids use were calculated by univariate and multivariate Cox regression analyses. The systematic review included relevant studies published before October 2018. The combined HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS) were calculated using random-effect models. A total of consecutive 203 cancer patients were included in the cohort study. Kaplan–Meier curves indicate a negative association between CSS and cancer-related pain or opioids requirement, but less evidence of an association with the dose of opioids use. Multivariate models revealed that the pain level and opioids requirement were associated with shorter CSS, after adjusting for significant covariates. The results of the meta-analysis indicated that postoperative opioids use had a poor effect on PFS, and opioids use for cancer-related pain was associated with poor OS in cancer patients, while intraoperative opioids use was not associated with cancer survival. We concluded that cancer-related pain and opioids requirements are associated with poor survival in advanced cancer patients, and postoperative opioids use and opioids use for cancer-related pain may have an adverse effect on the survival of cancer patients.

Sepsis-associated acute kidney injury (AKI) is a life threatening condition with high morbidity and mortality. The pathogenesis of AKI is associated with apoptosis. In this study, we investigated the effects of ligustrazine (LGZ) on experimental sepsis-associated AKI in mice. Sepsis-associated AKI was induced in a mice model using cecal ligation and puncture (CLP) method. Mice were administered LGZ (10, 30, and 60 mg/kg) via tail vein injection 0.5 h before CLP surgery. Mice survival was evaluated. Renal water content was detected. Urine samples were collected for ELISA of Kim1. Kidneys were collected for nucleic acid analysis and histological examination. Pathological assessment was used to determine the effect of LGZ on sepsis-associated AKI. Caspase-3 expression in kidney was assessed by immunohistochemistry. Renal NMDAR1 level was also determined. Treatment of LGZ improved mice survival rate; the effect was significant when administered at a high LGZ dose (60 mg/kg). Renal water content of mice undergoing CLP was significantly reduced by LGZ treatment. Both middle-dose and high-dose LGZ treatments reduced urine Kim1 level in sepsis-associated AKI mice. The severity of AKI in septic mice was reduced by middle-dose and high-dose LGZ administration. Immunohistochemical analysis revealed decreased caspase-3 and NMDAR1 levels in the kidney following middle-dose and high-dose LGZ treatments. RT-PCR assay showed a significant reduction in NMDAR1 mRNA expression in the kidney of middle-dose and high-dose LGZ-treated mice. LGZ exhibited protective effects against sepsis-associated AKI in mice, possibly via downregulation of renal NMDAR1 expression and its anti-apoptotic action by inhibiting caspase-3.