BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

Ocular surface squamous neoplasia(OSSN)is a series of pathological solid tumors formed by dysplasia of keratoconjunctival epithelium, which is one of the most common ocular surface tumors in adults. In the past two decades, the treatment of OSSN has gradually changed from surgical resection to topical chemotherapy. Interferons, 5-fluorouracil and mitomycin are the most commonly used topical agents for the clinical treatment of this disease. This paper summarizes the diagnosis of OSSN and various local chemotherapy treatment options, highlights the potential role of high-resolution optical coherence tomography(HR-OCT)technology in the diagnosis and treatment of this disease.

Objective To investigate the prognostic value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT imaging on extranodal nasal type natural killer/T-cell lymphoma (ENKTL).Methods Thirtyfive patients (20 males,15 females,average age 45 years) diagnosed as Ann Arbor stage Ⅰ-Ⅱ ENKTL from February 2013 to February 2016 were retrospectively analyzed.All patients were pathologically confirmed and underwent 18F-FDG PET/CT before treatment.The maximum standardized uptake value (SUVmax),international prognostic index score (IPI),serum lactate dehydrogenase (LDH),and immunohistochemical results were recorded.Patients were followed up for 2 years.The relationships between SUVmax,progression-free survival (PFS),pathological features and IPI were assessed using Fisher exact test.Results There were 18 ENKTL patients with progression,and 17 had no progression.Patients with SUVmax ≥ 12.2 had worse prognosis than those with SUVmax＜ 12.2 (P =0.001).There were correlations between SUVmax and Ki-67 (r=0.701,P=0.001),SUVmax and CD56 (r=0.393,P=0.032),SUVmax and IPI (r=0.787,P＜0.01),respectively.It was also found that SUVmax,Ki-67,CD56 and IPI were related to PFS (all P＜0.05).Conclusion SUVmax of 18F-FDG could be used as an important prognostic indicator for early ENKTL.

Objective To investigate the molecular mechanism of retinoic acid in targeted treatment of craniopharyngioma by detecting the expression of RARαand PPARβ/δin craniopharyngioma cells and analyzing the correlation between the expression and effect of retinoic acid. Methods The expression of RARα and PPARβ/δ in craniopharyngioma cells from 31 patients cultured in vitro was quantified by reverse transcription-PCR. The inhibition rates of RA on craniopharyngioma with different expression of RARα and PPARβ/δ were detected by using MTT assay, and the correlation between the expression of RARα and PPARβ/δand the effect of RA was analyzed. Results 1. The RT-PCR results showed that the expression levels of PPARβ/δand RARα mRNA were different. Craniopharyngioma cells from 31 patients in primary culture were divided into three groups according the expression levels of nuclear receptor: PPARβ/δ>RARα group, RARα>PPARβ/δ group and RARα>>PPARβ/δ group. 2.MTT results showed that the inhibition rate of RARα>>PPARβ/δgroup was significantly higher than the other groups under same drug, the differences had statistical significance ( <0.01) . Conclusions The expression of PPARβ/δ, RARα can be used to evaluate the effect of RA in treatment of craniopharyngioma. The craniopharyngioma with low-expression of PPARβ/δ is more sensitive to RA. Targeting higher RARα or targeting lower PPARβ/δ is beneficial to the treatment of craniopharyngiomas.