Objective:To investigate the prognostic significance of plasma fibrinogen (FIB) and D-dimer in elderly patients with non-small cell lung cancer (NSCLC) before any anti-cancer treatments.Methods:97 cases of patients with lung cancer (lung cancer group) and 36 healthy subjects (control group) were enrolled;the level of plasma D-dimer and FIB were compared;the relationship between their levels and clinical pathological factors of NSCLC as well as prognosis was analyzed.Results:The levels of plasma FIB and D-dimer in lung cancer group were higher than those in healthy control group (P＜0.05).FIB in lung cancer group was related to TNM stage,and D-dimer was related to lymph node metastasis and TNM stage.Univariate analysis showed that FIB,D-dimer,tumor size,lymph node metastasis and TNM staging were associated with overall survival time (OS) and progression free survival (PFS).Multivariate analysis revealed that only D-dimer and FIB were independent prognostic factors of patients with NSCLC.Conclusion:Detection of fibrinogen and D-dimer in elderly patients with NSCLC before anti-cancer treatment would be useful for prognosis and might provide a certain value for individualized therapy.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis