Ziwu-Liuzhu-guided combined external therapy promotes wound healing in postoperative perianal fistulizing Crohn’s disease

Table 1 Baseline characteristics of perianal fistulizing Crohn’s disease patients in the three treatment groups, mean ± SD/n (%)

Variable	Sitz bath group (n = 72)	Sitz bath plus acupoint application group (n = 69)	Ziwu-Liuzhu time-specific external treatment group (n = 76)	Statistic	P value
Age (years)	34.8 ± 9.1	35.6 ± 8.7	33.9 ± 8.4	F = 0.71	0.493
Male	42 (58.3)	39 (56.5)	44 (57.9)	χ2 = 0.05	0.973
BMI (kg/m2)	21.9 ± 2.6	22.3 ± 2.8	22.1 ± 2.5	F = 0.42	0.66
Smoking history	15 (20.8)	13 (18.8)	15 (19.7)	χ2 = 0.10	0.95
Alcohol consumption	12 (16.7)	11 (15.9)	13 (17.1)	χ2 = 0.05	0.973
Disease duration (months), median IQR	19.0 (12.0-28.0)	18.0 (11.0-27.0)	20.0 (13.0-29.0)	H = 0.86	0.651
Age at diagnosis (years)	31.2 ± 8.6	32.0 ± 8.3	30.7 ± 8.1	F = 0.52	0.596
Previous fistula surgery	21 (29.2)	20 (29.0)	22 (28.9)	χ2 = 0.00	0.999
Number of fistula tracts	1.6 ± 0.7	1.5 ± 0.6	1.6 ± 0.7	F = 0.48	0.62
Complex fistula	31 (43.1)	29 (42.0)	33 (43.4)	χ2 = 0.04	0.981
Preoperative CDAI score	256.4 ± 41.2	252.7 ± 39.6	254.1 ± 40.5	F = 0.16	0.853
Preoperative PDAI score	6.4 ± 1.2	6.3 ± 1.1	6.2 ± 1.2	F = 0.53	0.592
Preoperative VAS score	6.1 ± 1.3	5.9 ± 1.2	6.0 ± 1.3	F = 0.34	0.714
Preoperative GAD-7 score	9.2 ± 2.6	9.0 ± 2.4	9.1 ± 2.5	F = 0.13	0.878
CRP (mg/L)	31.8 ± 8.6	30.6 ± 8.1	31.1 ± 8.4	F = 0.34	0.713
TNF-α (pg/mL)	41.7 ± 9.5	40.9 ± 9.2	41.2 ± 9.4	F = 0.13	0.879
IL-6 (pg/mL)	33.6 ± 8.3	32.8 ± 7.9	33.1 ± 8.0	F = 0.16	0.85
White blood cell count (× 109/L)	8.9 ± 2.1	8.7 ± 2.0	8.8 ± 2.2	F = 0.14	0.867
Hemoglobin (g/L)	118.6 ± 15.2	120.1 ± 14.7	119.5 ± 15.0	F = 0.22	0.804
Albumin (g/L)	37.9 ± 4.5	38.4 ± 4.3	38.1 ± 4.6	F = 0.28	0.758

BMI: Body mass index; IQR: Interquartile range; CDAI: Crohn’s Disease Activity Index; PDAI: Perianal Disease Activity Index; VAS: Visual Analogue Scale; GAD-7: Generalized Anxiety Disorder-7 scale; CRP: C-reactive protein; TNF: Tumor necrosis factor; IL: Interleukin.

Table 2 Changes in Crohn’s Disease Activity Index and Perianal Disease Activity Index scores from baseline to week 4 among the three treatment groups, mean ± SD

Variable	Sitz bath group (n = 72)	Sitz bath plus acupoint application group (n = 69)	Ziwu-Liuzhu time-specific external treatment group (n = 76)	Statistic	P value	Effect size (η2)
CDAI score
Baseline	256.4 ± 41.2	252.7 ± 39.6	254.1 ± 40.5	F = 0.16	0.853	0.001
Week 4	183.7 ± 34.9	151.8 ± 30.6	121.6 ± 27.4	F = 57.32	< 0.001	0.347
Δ CDAI	72.7 ± 28.6	100.9 ± 30.2	132.5 ± 35.7	F = 61.08	< 0.001	0.362
95%CI for Δ CDAI	66.1-79.3	93.8-108.0	124.5-140.5
Within-group comparison (paired t)	t = 21.56	t = 27.75	t = 32.34		< 0.001 for all
PDAI score
Baseline	6.4 ± 1.2	6.3 ± 1.1	6.2 ± 1.2	F = 0.53	0.592	0.005
Week 4	4.3 ± 1.0	3.1 ± 0.9	2.0 ± 0.8	F = 98.46	< 0.001	0.478
Δ PDAI	2.1 ± 0.9	3.2 ± 1.0	4.2 ± 1.1	F = 74.92	< 0.001	0.411
95%CI for Δ PDAI	1.89-2.31	2.96-3.44	3.95-4.45
Within-group comparison (paired t)	t = 19.80	t = 26.59	t = 33.28		< 0.001 for all

Within-group comparisons were performed using paired t tests. Between-group comparisons were performed using one-way analysis of variance. Bonferroni correction was applied for post hoc pairwise comparisons. Effect size is expressed as eta-squared (η²). Δ indicates the change from baseline to week 4. CDAI: Crohn’s Disease Activity Index; PDAI: Perianal Disease Activity Index; CI: Confidence interval.

Table 3 Changes in Generalized Anxiety Disorder-7 scale scores and anxiety severity at baseline and week 4 among the three treatment groups, mean ± SD/n (%)

Group	Sitz bath (n = 72)	Sitz bath plus acupoint application group (n = 69)	Ziwu-Liuzhu time-specific external treatment (n = 76)
Baseline GAD-7	9.2 ± 2.6	9.0 ± 2.4	9.1 ± 2.5
Week 4 GAD-7	7.9 ± 2.4	5.8 ± 2.0	4.1 ± 1.7
Δ GAD-7	1.3 ± 1.6	3.2 ± 1.7	5.0 ± 1.9
Δ GAD-7 95%CI	0.9-1.7	2.8-3.6	4.6-5.4
Effect size (Cohen d)	0.5	1.36	2.22
Within-group t value	6.18	15.37	21.48
Within-group P value	< 0.001	< 0.001	< 0.001
No anxiety 0-4	13 (18.1)	22 (31.9)	40 (52.6)
Mild 5-9	38 (52.8)	34 (49.3)	29 (38.2)
Moderate 10-14	17 (23.6)	11 (15.9)	6 (7.9)
Severe ≥ 15	4 (5.5)	2 (2.9)	1 (1.3)

GAD-7: Generalized Anxiety Disorder-7 scale; CI: Confidence interval.

Table 4 Propensity score matching and sensitivity analysis results, mean ± SD/median interquartile range

Comparison	Indicator	Ziwu-Liuzhu time-specific external treatment group	Comparator group	Statistic	P value
Ziwu-Liuzhu time-specific external treatment vs sitz bath (PSM, n = 58 pairs)	Healing time (day)	19 (16-23)	29 (25-34)	Z = -5.21	< 0.001
	CRP after treatment (mg/L)	9.1 ± 4.3	17.8 ± 6.1	t = -8.64	< 0.001
	TNF-α after treatment (pg/mL)	17.1 ± 5.4	27.4 ± 7.6	t = -7.93	< 0.001
	IL-6 after treatment (pg/mL)	11.4 ± 4.7	20.6 ± 6.8	t = -8.11	< 0.001
	Total effective rate (%)	53/58 (91.4)	37/58 (63.8)	χ2 = 12.37	< 0.001
	Logistic regression OR (95%CI)	4.12 (1.89-8.97)	Reference		< 0.001
Ziwu-Liuzhu time-specific external treatment vs sitz bath plus acupoint application group (PSM, n = 61 pairs)	Healing time (day)	18 (15-22)	24 (20-28)	Z = -4.28	< 0.001
	VAS pain score	2.2 ± 0.9	3.3 ± 1.1	t = -5.43	< 0.001
	CRP after treatment (mg/L)	8.7 ± 4.0	13.4 ± 5.2	t = -5.58	< 0.001
	TNF-α after treatment (pg/mL)	16.5 ± 5.3	22.4 ± 6.4	t = -5.01	< 0.001
	IL-6 after treatment (pg/mL)	10.9 ± 4.5	16.2 ± 5.7	t = -5.32	< 0.001
	Total effective rate (%)	57/61 (93.4)	49/61 (80.3)	χ2 = 5.29	0.021
	Logistic regression OR (95%CI)	3.26 (1.28-8.29)	Reference		0.013

PSM: Propensity score matching; CRP: C-reactive protein; TNF: Tumor necrosis factor; IL: Interleukin; OR: Odds ratio; CI: Confidence interval; VAS: Visual Analogue Scale.