Objective: Pain is one of the most common symptoms of cancer patients. Patients with advanced stages of cancer are always transferred to primary medical institutions or treated with home medication due to their specific pathophysiological characteristics. Studies have shown that continuous pharmaceutical care can improve the effectiveness and safety of drug therapy for cancer pain patients in primary care, but no relevant research has been conducted in China. Based on the Delphi method, this study aims to construct a pharmaceutical care mode for cancer pain patients and analyze its effect in drug therapy treatment in primary care in China.Methods: A pharmaceutical care mode for cancer pain patients in primary care was developed through two rounds of expert consensus. A total of 200 cancer pain patients from January 2022 to January 2023 in Nanjing Drum Tower Hospital were recruited and divided into an intervention group and control group. The self-developed pharmaceutical care mode in primary care was conducted in the intervention group, while the traditional pharmaceutical care mode was conducted in the control group. Comparisons between the groups were performed in terms of pain assessment rate, reasonable rate of pain assessment, pain score, and incidence of adverse reactions.Results: The initiative of experts in the two rounds of consultation was 100%, with an authority coefficient of 0.83. The coordination coefficient of the second round was higher than that of the first round, indicating that the consistency of expert opinions was enhanced. There were 100 cases in each group, and 12 and 8 were lost to follow-up in the intervention group and control group, respectively. Compared with the control group, the intervention group had a significantly higher pain assessment rate, a reasonable rate of pain assessment, and a significantly lower pain score and incidence of adverse reactions.Conclusion: Under the scientific and reasonable mode of pharmaceutical care for cancer pain patients at the primary level, standardized drug therapy could significantly enhance the efficacy of treatment, thereby improving the quality of life of patients.

Objective:To investigate the distribution of blood concentration of cyclosporine (CsA) in patients with autoimmune disease in China, and analyze the effect of genetic polymorphisms of CsA-metabolizing enzymes, transporters and target enzymes on CsA levels.Methods:Steady-state trough blood concentrations (CsA C 0) of 193 patients' were detected by enzyme multiplied immunoassay technique. The genotype of the following sites in the included patients were sequenced by reverse transcription-polymerase chain reaction (RT-PCR): cytochrome P450 (CYP) 3A420230C>T, CYP3A56986A>G, ATP binding cassette subfamily B member 1 (ABCB1)1236C>T, ABCB12677G>T/A, ABCB13435C>T, cytochrome P450 oxidoreductase (POR) 1508 C>T and formyl peptide receptor 1 (FPR1) C>G were sequenced by RT-PCR. The influence of the gene polymorphism of the above-mentioned sites on the blood concentration of CsA was analyzed by using One-way analysis of variance (ANOVA), LSD- t test, Chi-square test. Results:One hundred and ninety-three patients included took CsA. The doses ranged from 75-200 mg/d and the patients' blood concentration distribution span was wide (33.0-313.8 ng/ml). The daily dose ( χ2=21.908, P=0.001) and age( F=4.262, P=0.006) had significant effect on the plasma concentration of CsA. ABCB12677G>T/A (rs2032582) gene polymorphism impacted on the unit dose of CsA C 0 (CsA C 0/d), CsA C 0/d [(0.81±0.42) ng·ml -1·mg -1] in wild type (GG) was higher than heterozygous mutant [GT/GA, (0.65±0.30) ng·ml -1·mg -1, P=0.023) and homozygous mutant (TT/AA/TA, (0.66±0.34) ng·ml -1·mg -1, P=0.039). Conclusion:The blood concentration of patients varies greatly among individuals. The Cold of CsA in wild type patients with ABCB12677G>T/A gene is signifficantly higher than that in mutant patients.

目的:研究参与甲氨蝶呤(MTX)代谢酶的基因多态性与中国类风湿关节炎(RA)患者疗效的相关性.方法:采用队列研究设计法,共纳入符合RA诊断并服用MTX的患者109例,按照入组标准分为有效组和无效组:有效组患者[稳定剂量的MTX治疗至少6个月、血细胞沉降率(ESR)<20 mm·h-1];无效组患者(稳定剂量的MTX治疗至少3个月,ESR改善低于20％).采用聚合酶链式反应限制性片段长度多态性分析技术,测定患者样本的RFC-1(rs1051266)、ABCB1(rs1045642)、MTHFR(rs1801131,rs1801133)、TYMS(rs2853542)、ATIC(rs2372536、rs12995526、rs3821353、rs7563206、rs16853834)、DHFR(rs408626、rs12517451、rs10072026、rs1643657)等的基因型.结果:TYMS(rs34743033)的基因型分布(2R2R/2R3R/3R3R)在有效组和无效组中进行纯合突变型(2R2R)与杂合基因型+野生基因型(2R3R+3R3R)进行χ2检验后得到的P值有统计学差异(χ2=5.69,P=0.02).结论:TYMS(rs34743033)的基因多态性可能影响RA患者对MTX的疗效反应,TYMS(rs34743033)含有三个重复序列的患者可预测使用MTX治疗6个月后有较好的疗效.

Objective:To determine the concentration of hydroxychloroquine (HCQ) and its active metabolite deethylhydroxychloroquine (DHCQ) in breast milk of lactating patients with autoimmune disease. To observe the safety of hydroxychloroquine in lactation period, and to explore the factors that may affect HCQ and DHCQ concentration in the milk.Methods:Lactating patients with autoimmune disease who have taken HCQ for at least 6 months were included in our study. A new high performance liquid chromatography (HPLC) method was established to detect HCQ and DHCQ levels in breast milk. Milk samples were collected at different time points: before taking the drug (0 hours), and 2 hours, 4 hours, 6 hours after taking the drug. In addition, the genotype of cytochrome CYP3A4*1G, CYP3A5*3 and CYP2D6*10 which were related to HCQ metabolism were tested by dideoxy chain termination method. Visual acuity, hearing and growth status of the patients' infants were followed up on a regular basis. T-test, one-way ANOVA and Pearson's test were used for data analysis. Results:In 15 patients, the average concentration of HCQ and DHCQ in the milk of patients taking 200 mg/d were (520±261) ng/ml and (177±112) ng/ml, respectively. While the average concentration of HCQ and DHCQ in the milk of patients taking 400 mg/d were (1 036±374) ng/ml and (397±271) ng/ml, respectively. The peak of HCQ level for 11 patients was at 4 hour after taking the drug, while the others' were at 2 hour. The breast-fed infants did not show any abnormal symptoms of hearing, vision and growth. However, cytochrome gene polymorphism did not affect the peak of HCQ and DHCQ.Conclusion:The concentration of HCQ and DHCQ in breast milk is positively correlated to the dosage. The peak level of HCQ milk is 4 hours after taking the drug. The levels of HCQ and DHCQ at 6 hours are similar as those in the whole blood. It is suggested that patients who take HCQ can feed 4 hours after taking the drug to reduce the HCQ and its active metabolites being absorbed by infants. However, the impact of HCQ on infant safety and gene polymorphism of CYP on milk concentration among individuals needs to be further verified in large sample studies and long-term follow-up.

目的:建立一种高效液相色谱法检测全血中羟氯喹及其代谢物去乙基羟氯喹、去乙基氯喹的新方法,并分析干燥综合征患者血药浓度与免疫相关临床指标的相关性.方法:取100μL全血样本,加入内标,以两倍量的乙腈沉淀蛋白,离心取上清进样.用Zorbax SB-C18色谱柱分离,流动相为0.2 mol·L-1磷酸二氢钾-乙腈=15∶85(磷酸调至pH3.0),流速1 mL·min-1,检测波长254 nm,柱温35℃.考察该方法的专属性、标准曲线和定量限、精密度和准确度、提取回收率、稳定性;测定53例患者羟氯喹及其代谢物血药浓度,并收集患者白细胞水平、血小板计数、谷丙转氨酶、谷草转氨酶、血细胞沉降率等临床检验指标,用SPSS软件分析血药浓度与临床指标的关系.结果:羟氯喹、去乙基羟氯喹、去乙基氯喹、内标氯喹的保留时间分别在8.6,4.1,5.2 min和12.8 min左右,羟氯喹及其代谢物在3～3000 ng· mL-1范围内线性良好,最低定量限为3ng·mL-1,批内、批间精密度、方法回收率符合要求;患者用药后白细胞水平有明显降低,其他临床指标无明显变化,血药浓度高组患者白细胞水平较高,其他指标在高低浓度组间没有明显差异.结论:该方法灵敏度高、结果准确、样品处理简单、分析快速,可用于临床检测.干燥综合征患者服用羟氯喹后白细胞计数有统计学差异,服药后高浓度组患者白细胞计数显著高于低浓度组患者.

糖皮质激素(GC)在自身免疫性疾病的治疗中发挥重要作用,其诱导的骨质疏松症(GIOP)为治疗引起的主要不良反应.由于对GIOP缺乏充分认知,很多长期服用GC的患者未进行及时合理的预防及治疗.根据相关文献及最新指南,重点介绍了GIOP的发病率、发生机制、危险因素及防治方法,为临床防治GIOP提供参考.