探讨热毒宁联合甘草酸苷治疗，对第2期手足口病(HFMD)患儿免疫功能的影响。

选择2017年1月至2019年10月，在南宁市第二人民医院诊治的286例第2期HFMD患儿为研究对象，并将其纳入观察组。按照随机数字表法，将观察组患儿随机分为4个亚组后，再对其采取不同治疗方法，热毒宁亚组(n＝73，采用热毒宁治疗)，甘草酸苷亚组(n＝72，采用甘草酸苷治疗)，联合治疗亚组(n＝75，采用热毒宁＋甘草酸苷治疗)及常规治疗亚组(n＝66，采用常规治疗措施)。选择同期在本院进行体检的健康儿童作为对照组(n＝63)。采用流式细胞术，检测所有受试儿外周血中T细胞、辅助T细胞(Th)、细胞毒性T细胞(Tc)、自然杀伤(NK)细胞和B细胞所占淋巴细胞的百分比；采用免疫比浊法，检测其血清免疫球蛋白(Ig)G、IgM及IgA水平。采用独立样本t检验，单因素方差分析及最小显著性差异法(LSD)-t，分别对观察组与对照组，以及4个亚组受试儿的上述指标进行统计学比较；采用Pearson相关分析法，对HFMD患儿血清IgM水平与外周血淋巴细胞中B细胞百分比的相关性进行分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。

①观察组第2期HFMD患儿的外周血淋巴细胞中T细胞、Th及NK细胞百分比，Th百分比与Tc百分比比值(Th/Tc)，以及血清IgG、IgA水平，均显著低于对照组；而外周血淋巴细胞中B细胞百分比及血清IgM水平，则显著高于对照组，并且差异均有统计学意义(P<0.05)。②热毒宁亚组、甘草酸苷亚组和联合治疗亚组患儿的外周血淋巴细胞中T细胞及Th百分比，以及血清IgG水平，分别为(55.9±9.4)%、(33.7±7.7)%及(10.9±2.4) g/L，(57.2±8.9)%、(35.3±7.3)%及(11.2±2.9) g/L，(58.8±9.9)%、(36.5±7.3)%及(11.8±2.9) g/L，均分别高于常规治疗亚组的(51.3±11.9)%、(29.8±6.8)%及(9.3±2.8) g/L；而外周血淋巴细胞中B细胞百分比、血清IgM及IgA水平，分别为(22.8±5.2)%、(1.7±0.5) g/L及(0.79±0.26) g/L，(21.9±4.9)%、(1.7±0.4) g/L及(0.81±0.17) g/L与(20.9±5.6)%、(1.6±0.5) g/L及(0.84± 0.23) g/L，则均分别低于常规治疗亚组的(24.5±5.3)%、(1.8±0.4) g/L及(0.89±0.20) g/L，并且差异均有统计学意义(P＝0.012、P＝0.002及P<0.001，P＝0.001、P<0.001及P<0.001，P<0.001、P<0.001及P<0.001；P＝0.022、P＝0.047及P＝0.013，P＝0.014、P＝0.043及P＝0.013，P＝0.003、P＝0.014及P＝0.046)。③联合治疗亚组患儿的外周血淋巴细胞中Th百分比，Th/Tc(2.0±0.4)，以及血清IgG、IgA水平，均高于热毒宁亚组[Th/Tc为(1.8±0.4)]；而外周血淋巴细胞中B细胞百分比，则低于热毒宁亚组，并且差异均有统计学意义(P＝0.026、0.003、0.042、0.047，P＝0.025)。④联合治疗亚组与甘草酸苷亚组患儿的上述9项指标比较，差异均无统计学意义(P>0.05)。⑤相关性分析结果显示，第2期HFMD患儿的血清IgM水平与外周血淋巴细胞中B细胞百分比，呈正相关关系(r＝0.841，P＝0.018)。

热毒宁及甘草酸苷均能显著改善第2期HFMD患儿的免疫功能紊乱。但是，二者联合是否较单独治疗对该病患儿免疫功能紊乱的改善作用更佳，则尚需进一步研究、证实。

To investigate effects of treatment of reduning combined with glycyrrhizin on immune function in children with the second stage of hand foot and mouth disease (HFMD).

From January 2017 to October 2019, a total of 286 children with the second stage of HFMD in the Second Nanning People′s Hospital were selected as research subjects, and they were included into observation group. According to random digits table method, cases in observation group were randomly divided into 4 subgroups which were reduning subgroup (n=73, treated with reduning), glycyrrhizin subgroup (n=72, treated with glycyrrhizin), combined treatment subgroup (n=75, treated with reduning and glycyrrhizin) and routine treatment subgroup (n=66, with routine treatment). Healthy children who had physical examination in the same hospital at the same time were selected as control group (n=63). Flow cytometry was used to detect the percentage of T cells, helper T cell (Th), cytotoxic T lymphocyte (Tc), natural killer (NK) cell and B cells in peripheral blood lymphocytes of all subjects; the levels of serum immunoglobulin (Ig)G, IgM and IgA were detected by immunoturbidimetry method. Independent-samples t test was used to compare the above indexes between observation group and control group; one-way ANOVA and least significant difference (LSD)-t test were used to compare the above indexes among 4 subgroups and further comparison between any 2 subgroups. Pearson correlation analysis was used to analyze the correlation between serum IgM level and the percentage of B cells in peripheral blood lymphocytes of HFMD children. The procedure followed in this study was consistent with World Medical Association Declaration of Helsinki revised in 2013.

① The percentages of T cells, Th and NK cell in peripheral blood lymphocytes, ratio of Th percentage to Tc percentage (Th/Tc), and levels of serum IgG and IgA in observation group of children with the second stage of HFMD were significantly lower than those in control group; while the percentage of B cells in peripheral blood lymphocytes and serum IgM level in observation group were significantly higher than those in control group, and the differences were statistically significant (P<0.05). ② The percentages of T cells and Th in peripheral blood lymphocytes, and serum IgG levels in reduning subgroup, glycyrrhizin subgroup and combined treatment subgroup of children were (55.9±9.4)%, (33.7±7.7)%, (10.9±2.4) g/L; (57.2±8.9)%, (35.3±7.3)%, (11.2±2.9) g/L; (58.8±9.9)%, (36.5±7.3)%, (11.8± 2.9) g/L, respectively, which were significantly higher than those of (51.3±11.9)%, (29.8±6.8)%, (9.3±2.8) g/L respectively in routine treatment subgroup; while the percentages of B cells in peripheral blood lymphocytes, and serum IgM and IgA levels in those three subgroups were (22.8±5.2)%, (1.7±0.5) g/L, (0.79±0.26) g/L; (21.9±4.9)%, (1.7±0.4) g/L, (0.81±0.17) g/L; (20.9±5.6)%, (1.6±0.5) g/L, (0.84±0.23) g/L, respectively, which were significantly lower than those of (24.5±5.3)%, (1.8±0.4) g/L, (0.89±0.20) g/L, respectively in routine treatment subgroup; and all differences above were statistically significant (P=0.012, P=0.002, P<0.001; P=0.001, P<0.001, P<0.001; P<0.001, P<0.001, P<0.001; P=0.022, P=0.047, P=0.013; P=0.014, P=0.043, P=0.013; P=0.003, P=0.014, P=0.046). ③ The percentages of Th in peripheral blood lymphocytes, Th/Tc (2.0±0.4), and serum IgG and IgA levels in combined treatment subgroup of children were higher than those in reduning subgroup[Th/Tc was (1.8±0.4)], while the percentage of B cells in peripheral blood lymphocytes was lower than that in reduning subgroup, and all differences above were statistically significant (P=0.026, 0.003, 0.042, 0.047; P=0.025). ④ There were no significant differences between combined treatment subgroup and glycyrrhizin subgroup of children in above mentioned 9 indexes (P>0.05). ⑤ Correlation analysis showed that there was a positive correlation between serum IgM level and percentage of B cells in peripheral blood lymphocytes in children with the second stage of HFMD (r=0.841, P=0.018).

Reduning and glycyrrhizin can significantly improve immune dysfunction in children with the second stage of HFMD. However, whether combination treatment by both of them is better than that of single one needs further to study.