Objective:To explore the relationship between reduced folate carrier 1(RFC1) gene polymorphism a curative effect, plasma concentration and adverse reaction of methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods:A total of 268 RA patients with 82 males and 186 females, aged (52.47±10.29) years, who received MTX treatment in the First People's Hospital of Shangqiu, from Jan 20, 2018 to Jan 20, 2021 were collected by case-control study. The genotype of RFC1 G80A locus were detected. The plasma concentration of MTX were detected after initial administration for 48 hours. The curative effect and adverse reactions were observed and counted after treatment for 6 months. The differences of RFC1 G80A genotype among different groups were compared. Collinearity diagnosis and logistic regression were used to analyze the influencing factors of MTX efficacy and plasma concentration. The incidences of adverse reactions among patients with different genotype were compared by Chi-square test.Results:The distribution of RFC1 G80A genotype (GG/GA/AA) and gene frequency (G/A) showed statistically significant differences between the effective group and the ineffective group (χ 2=6.583, P=0.037; χ 2=6.249, P=0.012), and the effective rate of AA type [59.26% (32/54)] was higher than that of GG type [36.49% (27/74)] (χ 2=6.516, P=0.011). Logistic regression analysis showed that the OR (95% CI) value of MTX response rate in AA genotype patients versus GG genotype patients was 2.491(1.206-5.144). The 48 hour plasma drug concentration of AA type patients was 1.15 (0.75, 1.35) μmol/L. Compared with GG type [0.74 (0.61, 1.18) μmol/L] and GA type [0.84 (0.69, 0.99) μmol/L], the difference was statistically significant(χ 2=7.152, P=0.028). Logistic regression analysis showed that the probability of high 48 hour plasma drug concentration in patients with AA type was approximately 2.583 (1.238-5.390) times higher than that in patients with GG type. There was a statistically significant difference in the incidence of liver function injury among three different genotypes (GG/GA/AA) (χ 2=12.606, P=0.002). Conclusion:RFC1 G80A locus polymorphism can affect the MTX efficacy, blood drug concentration and liver function damage in RA patients. AA type patients have better efficacy and higher blood drug concentration compared to GG type patients, but the rate of liver function damage is also higher.

Objective:To assess the impact of preoperative short-course radiotherapy combined with neoadjuvant chemotherapy on elderly patients with locally advanced rectal cancer after a 2-year follow-up.Methods:In this retrospective cohort study, we included 446 consecutive cases of elderly patients diagnosed and treated for locally advanced rectal cancer(stage Ⅱ-Ⅲ with T3-T4 and/or positive regional lymph nodes)at the First People's Hospital of Shangqiu city from January 2012 to December 2019.The patients were divided into two groups based on the treatment method: an observation group(107 cases)and a control group(339 cases).The patients in the observation group underwent preoperative short-course radiotherapy combined with neoadjuvant chemotherapy.The regimen included short-term radiotherapy(25 Gy over 1 week in 5 fractions)followed by 4 courses of chemotherapy(CAPOX regimen).On the other hand, the control group received concurrent radiotherapy and chemotherapy.The regimen involved 50 Gy over 5 weeks in 25 fractions and concurrent capecitabine chemotherapy.Afterward, total rectal mesentery resection was performed, and postoperatively, 2 and 6 courses of CAPOX chemotherapy were continued.Follow-up was conducted until 31 December 2021, with the primary observation being the disease-free survival(DFS)of patients in both groups.Secondary observations included overall survival(OS)time, lesion progression-free survival(PFS)time, local recurrence rate, and the rate of acute toxicity events.Cox regression analyses were conducted to compare the factors influencing DFS.Results:Among the 446 patients, 303(67.9%)were male and 143(32.1%)were female.The patients in the observation group were found to be younger and had a higher proportion of Eastern Collaborative Oncology Group(ECOG)physical status score 0 compared to the control group(both P<0.05).Additionally, the two groups differed significantly in terms of MRI T stage, N stage, distance from the external anal verge, rectal mesorectal fascial infiltration, pathological stage, and chemotherapy-to-surgery time interval(all P<0.05).Throughout a mean follow-up period of(20.7±3.5)months, there were 76 deaths, 89 distant metastases, and 32 local recurrences.The results of Kaplan-Meier survival analysis revealed that the observation group had a higher disease-free survival(DFS)rate at 2 years of follow-up compared to the control group[73.8%(79/107) vs.68.1%(231/339), Log-rank χ2=2.676, P=0.041].Additionally, the median DFS time was longer in the observation group[19(12, 22)months]compared to the control group[16(11, 19)months]( Z=2.774, P=0.038).Furthermore, the observation group exhibited a significantly longer OS time[26(21, 33)months]compared to the control group[22(18, 14)months]( Z=2.879, P=0.032).However, the median PFS time was similar in both groups[20(14, 25)months vs.16(12, 21)months]( Z=1.545, P=0.123).The incidence of distant metastasis was 18.7%(20/107)in the observation group and 20.4%(69/339)in the control group(Log-rank χ2=0.341, P=0.708), indicating no significant difference.Similarly, there was no significant difference in the risk of local recurrence between the observation group[9.3%(10/107)]and the control group[6.5%(22/339)](Log-rank χ2=0.996, P=0.318).In terms of adverse reactions, there was no statistically significant difference in the incidence of grade≥3 acute toxic reactions between the two groups[19.6%(21/107) vs.12.1%(41/339), Log-rank χ2=1.661, P=0.148].A multifactorial Cox regression analysis revealed that age( HR=0.586, P=0.005), ECOG score( HR=0.721, P=0.028), MRI T-stage( HR=0.605, P=0.008), rectal mesenteric fascial infiltration( HR=1.649, P=0.012), and distance from the external anal verge( HR=0.638, P=0.041)were associated with DFS. Conclusions:The findings indicate that the combination of preoperative short-course radiotherapy and neoadjuvant chemotherapy in elderly patients with locally advanced rectal cancer demonstrates favorable short-term effectiveness and safety.This approach shows promise in improving outcomes for elderly patients with locally advanced rectal cancer.

Objective To investigate effect of stanniocalcin-1 (STC1) gene on the proliferation,apoptosis and radiotherapy sensitivity of non-small cell lung cancer.Methods The STC1 siRNA (STC 1-siRNA) and the non-interfering siRNA (negative control group) were transfected into the human lung cancer A549 cells by LipofectamineTM2000,and the blank control group was established.The expression level of STC1 protein was detected after transfection for 48 h by Western blotting.Clone forming test was adopted to detect the proliferation of A549 cells after STC1-siRNA and irradiation treatment.CCK8 assay was performed to detect the cell viability after treatment with STC1-siRNA and STC1-siRNA+8 Gy.The cell apoptosis was detected by flow cytometry.The expression levels of Ki67,Bax,STAT3 and p-STAT3 proteins were quantitatively measured by Western blotting.Results The expression level of STC1 protein in the A549 cells transfected with STC1-siRNA was significantly down-regulated than that in the blank control group (P＜ 0.05).Compared with the blank control group,the sensitization ratio was significantly enhanced after STC1-siRNA transfection.Compared with the blank control group,the cell viability and the expression levels of Ki67 and p-STAT3 protein were significantly decreased,whereas the apoptosis rate and the expression of Bax protein were significantly increased in the STC1-siRNA group.Compared with the STC1-siRNA group,the cell viability and the expression levels of Ki67 and p-STAT3 proteins were significantly decreased,whereas the cell apoptosis rate and the expression of Bax protein were remarkably increased in the STC1-siRNA+ 8 Gy group (all P＜0.05).Conclusion Inhibition of STC1 gene expression can enhance the radiotherapy sensitivity and down-regulate the STAT3 signaling pathway in non-small cell lung cancer.