Abstract
Purpose
This study aimed to investigate the associations between traditional Chinese Medicine (TCM) syndromes of acute pancreatitis (AP) and clinical biomarkers, imaging findings, and severity of AP.
Patients and Methods
A two-center retrospective analysis was conducted on 132 AP patients from Guang’anmen Hospital (n = 105) and Shandong University of TCM Hospital (n = 27). TCM syndrome classification of AP was performed according to the consensus of integrative diagnosis and treatment of AP in 2025. The clinical data were obtained from each participant, including clinical, laboratory and radiographic features, and TCM syndrome classification.
Results
A total of 132 patients were included from the two centers. No significant differences were observed among the three TCM syndrome groups in sex, age, glucose levels, AP severity, or pleural effusion volume (P > 0.05). Univariable and multivariable analyses yielded consistent results. After adjustment for age, sex, and AP severity, significant overall differences among syndrome groups were observed for C-reactive protein (CRP, P = 0.014), fibrinogen (FIB, P = 0.024), and total bilirubin (TBIL, P = 0.039). Compared with liver and gallbladder dampness-heat syndrome, liver depression and Qi stagnation syndrome was independently associated with elevated CRP (OR = 5.30, 95% CI: 1.73–16.19, P < 0.01), FIB (β = 1.34, 95% CI: 0.37–2.30, P < 0.01), and TBIL (OR = 4.32, 95% CI: 1.14–16.36, P < 0.05), while excess heat accumulation in the viscera syndrome was independently associated with elevated CRP (OR = 3.68, 95% CI: 1.01–13.37, P < 0.05).
Conclusion
Although TCM syndromes did not correspond to differences in AP severity, CRP, FIB, and TBIL varied significantly across syndromes. These findings suggest potential biological heterogeneity across TCM syndromes and require further validation.
Keywords: acute pancreatitis, traditional Chinese medicine, syndrome, retrospective analysis
Introduction
Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory condition of the pancreas, which is characterized by rapid onset of abdominal pain and elevated pancreatic enzymes.1,2 According to the presence and duration of organ failure and complications, AP is divided into three types: mild AP (MAP), moderate to severe AP (MSAP) and severe AP (SAP).3 The overall mortality rate of AP is estimated to be 3–7%, whereas SAP is associated with a markedly higher mortality rate of approximately 15–30%.4–6 Although the pathogenesis of AP remains incompletely understood, metabolic and inflammatory disturbances are thought to play key roles in its development.7 At present, the combination of Chinese and Western medicine has become the main treatment for this disease.8 Chinese medicine enema and traditional Chinese medicine (TCM) formulas have certain advantages in the treatment of AP.9,10 In addition, the Chinese medicine “preventive treatment” concept also has a certain guiding role in the clinical prevention and treatment of AP.11
In view of this, the Chinese Association of TCM announced the “Expert Consensus on the Diagnosis and Treatment of AP in TCM” in 2017.12 In recent years, with the progress of TCM research in AP, it is necessary to update the consensus on the diagnosis and treatment of TCM to meet the needs of clinical diagnosis and treatment. In 2023, the Chinese Association of TCM Spleen and Stomach Diseases Branch took the lead in establishing the drafting group of the “Expert Consensus on the Diagnosis and Treatment of AP in TCM”.13,14 As the basic pathogenesis of AP is ascending and descending disorder of spleen and stomach, liver failing to maintain normal Qi, and stomach disharmony due to Qi stagnation, dampness heat, blood stasis, the major TCM syndrome of AP was classified into six categories, including liver depression and Qi stagnation, liver and gallbladder dampness and heat, excess heat accumulation in the viscera, chest binding and interior excess, blood stasis binds, and internal blockage and external collapse.14
Previous studies have suggested potential associations between TCM syndromes and disease severity15 or laboratory abnormalities in AP, including C-reactive protein (CRP) and total bilirubin (TBIL).16 Excess-heat syndromes appear more frequent in severe AP, whereas liver depression and Qi stagnation syndrome may predominate in the early stage.15 In addition, liver and gallbladder dampness-heat syndrome has been reported to be positively associated with TBIL, which may have potential diagnostic value for this syndrome.16 However, these findings remain preliminary and evidence linking syndrome differentiation with objective clinical and biochemical characteristics is still limited. Conventional severity scoring systems primarily assess disease severity and prognosis but do not capture biological heterogeneity among patients.17 Therefore, TCM syndrome classification may provide complementary stratification reflecting different biological profiles.18 Recent work has highlighted a shift in TCM research toward more systematic and precision-oriented approaches, reinforcing its potential value in disease stratification.19 We hypothesized that different TCM syndromes may represent distinct biological profiles. This exploratory study aimed to compare clinical, laboratory, and radiological characteristics across different TCM syndromes in AP and to investigate their potential associations with objective clinical indicators.
Materials and Methods
Participants
In this two-center retrospective analysis, we collected the participants who were admitted into two centers including Guang’anmen Hospital (GAMH) and The Affiliated Hospital of Shandong University of TCM (AHSUTCM) between January 2015 and April 2024. This study was performed according to the convention of the Declaration of Helsinki, and ethical approval for the retrospective analysis of previously collected anonymized data was obtained in 2025 (Approval No.: 2025-ky-030) from the Ethics Committee of Guang’anmen Hospital. Due to the retrospective nature of the study and the use of anonymized clinical data, the Ethics Committee formally waived the requirement for informed consent. The study flowchart was shown in Figure 1.
Figure 1.
Study flowchart.
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera.
AP Diagnosis
AP was diagnosed according to the 2012 Revised Atlanta Classification (RAC) criteria: abdominal pain consistent with AP, acute onset of severe epigastric and persistent pains that are often radiating to the back; higher serum lipase (LPS) or amylase (AMY) activity than the normal range; and typical features of AP on CT or magnetic resonance imaging.20 Those who met two criteria were confirmed with AP. The inclusion criteria were: those aged 18 years or more; received thoracic CT examinations; and received no treatment before the initial onset of AP. Patients with a history of pleural effusion (PE) caused by organic lesions of the heart, lungs, kidneys, rheumatoid autoimmune diseases, and malignant tumors were excluded from this study. Besides, patients with incomplete clinical data, and patients who used special drugs such as hormones for a long time, were also excluded.
TCM Syndrome Classification of AP
The TCM syndrome classification of AP was performed according to the consensus of integrative diagnosis and treatment of acute-pancreatitis proposed by Spleen and Stomach Disease Branch of the China Association of Chinese Medicine in 2023.13,14 The major TCM syndrome classification of AP consists of the following syndromes: (a) syndrome of liver depression and Qi stagnation, (b) syndrome of liver and gallbladder dampness and heat, (c) syndrome of excess heat accumulation in the viscera, (d) syndrome of chest binding and interior excess, (e) syndrome of blood stasis binds, and (f) syndrome of internal blockage and external collapse. During the study period, only patients with syndrome types (a), (b), and (c) were identified in clinical practice; therefore, only these three syndrome groups were included in the analysis.
The diagnostic criteria for the syndromes included in this study were as follows. Syndrome of liver depression and Qi stagnation was characterized by: main symptoms including (1) epigastric and abdominal distension and pain and (2) distension and pain of the bilateral hypochondrium relieved with a fart; secondary symptoms including (1) frequent sighing, (2) nausea or vomiting, (3) belching, and (4) poor bowel movement. Tongue and pulse manifestations included a pale-red tongue with a thin white or thin yellow coating, and a wiry and tight or wiry and rapid pulse. Syndrome of liver and gallbladder dampness and heat was characterized by: main symptoms including (1) epigastric and abdominal distension and pain and (2) sticky or difficult defecation; secondary symptoms including (1) chest oppression and discomfort, (2) fever, (3) dry mouth and bitter taste, (4) scanty and dark urine, and (5) jaundice of the eyes and body. Tongue and pulse manifestations included a red tongue with a yellow greasy or thin yellow coating, and a wiry and rapid pulse. Syndrome of excess heat accumulation in the viscera was characterized by: main symptoms including (1) abdominal fullness with hard pain and refusal to palpation and (2) dry, hard stool with constipation or obstruction of defecation; secondary symptoms including (1) afternoon tidal fever, (2) vomiting, (3) halitosis, and (4) scanty dark urine. Tongue and pulse manifestations included a red tongue with a yellow thick greasy coating or dry yellow coating, and a forceful and large or slippery and rapid pulse.14 The diagnosis was established when patients met both main symptoms and at least two secondary symptoms, or when the first main symptom and at least three secondary symptoms were present, with tongue and pulse manifestations considered as supportive diagnostic criteria. TCM syndrome classification was performed by an associate chief physician and a trained researcher based on the Expert Consensus on Traditional Chinese Medicine Diagnosis and Treatment of Acute Pancreatitis (2023). Only patients with concordant syndrome differentiation between the two evaluators were included in the final analysis.
Data Collection
The following clinical data were obtained from each participant, including TCM syndrome classification, clinical, laboratory and radiographical findings. The laboratory data included white blood cell (WBC), platelet (PLT), glucose, albumin (ALB), TBIL, direct bilirubin (DBIL), indirect bilirubin (IDBIL), aspartate transaminase (AST), alanine aminotransferase (ALT), alpha-amylase (α-AMY), lipase (LPS), CRP, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time (TT). Clinical data included gender, age, and AP severity. The pleural effusion volume (PEV) was the radiographical indicator. TCM syndrome classification was performed by two experienced staff blinded to the study design, and a comprehensive discussion was held in the presence of any disputes until consensus. A complete-case analysis was performed, and patients with missing values in any variables included in the analyses were excluded.
Determination of PEV
CT images were scanned by Siemens CT equipment, followed by homogenization. Two experienced radiologists, blinded to all clinical information, independently delineated PE boundaries on each slice using 3D Slicer software (version 5.5.0). The segmented images were automatically reconstructed into three-dimensional regions of interest (ROIs), and PEV was calculated. The determination of the PEV was performed as shown in Figure 2. To reduce measurement variability, the final PEV was defined as the mean value of the measurements obtained by the two radiologists.
Figure 2.
The volume of PE was measured using 3D Slicer software. (A) The extent of PE on the chest CT image. (B) The 3D image of PE after outlining. (C) Extent of PE on the coronal image of chest CT. (D) extent of PE on the sagittal image of chest CT.
Statistical Analysis
The measurement data were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR), and the categorical data were expressed as frequency (percentage). For inter-group comparison, the chi-square test or Fisher’s exact test was used for categorical variables; the continuous variables were analyzed by one-way analysis of variance (ANOVA) or Kruskal–Wallis H-test according to the normality test results. For variables showing statistically significant differences among syndrome groups in univariable analyses, post hoc pairwise comparisons were performed using Bonferroni correction to account for multiple testing, and adjusted P values were reported. TCM syndrome classifications of AP were considered as the independent variable, while clinical and laboratory parameters were treated as dependent variables.
To further control for potential confounding, multivariable regression analyses were performed to evaluate the associations between syndrome patterns and relevant clinical indicators. Covariates were prespecified and included in the models based on their clinical relevance and potential confounding effects, rather than selected according to the results of univariable analyses. Appropriate regression models were selected based on the nature and distribution of variables. Logistic regression model was used for categorical outcome variables, and the multiple linear regression model was used for continuous outcome variables. All tests were two-sided, and P < 0.05 was used as the criterion for statistically significant differences. For variables that remained statistically significant after multivariable adjustment, effect sizes were further estimated and reported as odds ratio (OR) or regression coefficients (β) with corresponding 95% confidence interval (CI).
Results
Characteristics of the Participants
As shown in Figure 1, 132 patients were eventually included in the two centers (GAMH: 105; AHSUTCM: 27). Among these patients, 89 showed a syndrome of liver and gallbladder dampness and heat, 25 showed a syndrome of liver depression and Qi stagnation, and 18 with syndrome of excess heat accumulation in the viscera. Female accounted for a lower proportion compared with male in the syndrome of liver and gallbladder dampness and heat (37.08% vs 62.92%), syndrome of liver depression and Qi stagnation (28.00% vs 72.00%), and syndrome of excess heat accumulation in the viscera (33.33% vs 66.67%). There were no statistical differences in the sex (P = 0.694), age (P = 0.363) and glucose (P = 0.064) among the three AP syndromes. In addition, there were no statistical differences in the AP severity among the three AP syndromes (P = 0.204) (Table 1). The overall missing data rates were low to moderate across variables. LPS showed the highest missing proportion (18.52%), followed by CRP (14.81%) and amylase (10.58%). Most other laboratory parameters had missing rates below 7% (Table S1).
Table 1.
Patients’ Characteristics
| Parameters | AP Syndrome | P Value | ||
|---|---|---|---|---|
| LGDH (n = 89) | LDQS (n = 25) | EHAV (n = 18) | ||
| Sex, female | 33 (37.08%) | 7 (28.00%) | 6 (33.33%) | 0.694 |
| Age | 54.29 ± 16.69 | 58.12 ± 17.48 | 59.50 ± 17.05 | 0.363 |
| SAP | 14 (15.73%) | 5 (20.00%) | 6 (33.33%) | 0.204 |
| Glucose, median [IQR] | 8.10 [6.82, 12.66] | 8.88 [7.30, 11.23] | 7.34 [5.42, 9.30] | 0.064 |
Abbreviations: AP, acute pancreatitis; LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; SAP, severe acute pancreatitis; IQR, interquartile range.
Overall Group Differences in Univariate Analysis
Univariate analysis was first performed to assess overall differences among the three AP syndrome groups. No statistically significant differences were observed in PEV, LPS, or α-AMY (P > 0.05) (Table 2). Regarding liver function-related parameters, no significant differences were found in ALB, DBIL, IDBIL, AST, or ALT (P > 0.05) (Table 3). However, TBIL showed a statistically significant difference among the three groups (P < 0.05). For inflammatory and hematological indices, CRP showed significant overall differences (P < 0.05), whereas WBC and PLT did not differ significantly among groups (P > 0.05) (Table 4). In coagulation parameters, FIB showed a significant difference (P < 0.05), while PT, APTT, and TT showed no significant differences (P > 0.05).
Table 2.
Comparison of PE, LPS and α-AMY Among Patients with Different AP Syndrome Classifications
| Variables | AP Syndrome | Univariate P Value | Multivariable Regression P Value* | ||
|---|---|---|---|---|---|
| LGDH (n = 89) | LDQS (n = 25) | EHAV (n = 18) | |||
| PE, presence (%) | 27 (30.34) | 8 (32.00) | 8 (44.44) | 0.506 | 0.942# |
| α-AMY, >135 (%) | 57 (64.04) | 11 (44.00) | 14 (77.78) | 0.064 | 0.053# |
| LPS, >51.3 (%) | 73 (82.02) | 19 (76.00) | 16 (88.89) | 0.555 | 0.593# |
Notes: *adjusted for age, gender, and AP severity using multivariable regression analysis; #using logistic regression.
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; AP, acute pancreatitis; PE, pleural effusion; LPS, lipase; α-AMY, alpha-amylase.
Table 3.
Comparison of ALB, TBIL, DBIL, IDBIL, AST and ALT Among Patients with Different AP Syndrome Classifications
| Variables | AP Syndrome | Univariate P Value | Multivariable Regression P Value * | ||
|---|---|---|---|---|---|
| LGDH (n = 89) | LDQS (n = 25) | EHAV (n = 18) | |||
| ALB | 39.14 ± 5.59 | 36.83 ± 4.62 | 36.94 ± 6.04 | 0.088 | 0.162§ |
| TBIL, >21 (%) | 42 (47.19) | 7 (28.00) | 3 (16.67) | 0.023 | 0.039# |
| DBIL, >3.4 (%) | 52 (58.43) | 14 (56.00) | 10 (55.56) | 0.960 | 0.847# |
| IDBIL, >17.6 (%) | 31 (34.83) | 5 (20.00) | 2 (11.11) | 0.072 | 0.117# |
| AST, >40 (%) | 29 (32.58) | 6 (24.00) | 7 (38.89) | 0.565 | 0.557# |
| ALT, >50 (%) | 24 (26.97) | 8 (32.00) | 5 (27.78) | 0.884 | 0.930# |
Notes: *adjusted for age, gender, and AP severity using multivariable regression analysis; #using logistic regression; §using multiple linear regression.
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; ALB, albumin; TBIL, total bilirubin; DBIL, direct bilirubin; IDBIL, indirect bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
Table 4.
Comparison of WBC, PLT, CRP and Coagulation Test
| Variables | AP Syndrome | Univariate P Value | Multivariable Regression P Value* | ||
|---|---|---|---|---|---|
| LGDH (n = 89) | LDQS (n = 25) | EHAV (n = 18) | |||
| CRP >10 (%) | 63 (70.79) | 16 (64.00) | 6 (33.33) | 0.010 | 0.014# |
| WBC | 12.19 ± 4.22 | 12.46 ± 4.37 | 11.30 ± 3.48 | 0.642 | 0.618§ |
| PLT | 231.0 ± 67.78 | 244.08 ± 86.46 | 232.72 ± 70.96 | 0.724 | 0.501§ |
| PT | 13.18 ± 2.06 | 13.61 ± 1.78 | 13.76 ± 4.28 | 0.548 | 0.898§ |
| APTT | 29.26 ± 4.81 | 30.32 ± 6.83 | 26.93 ± 4.95 | 0.110 | 0.132§ |
| FIB | 4.93 ± 2.05 | 4.44 ± 1.79 | 3.58 ± 1.14 | 0.022 | 0.024§ |
| TT | 15.94 ± 2.07 | 15.49 ± 1.54 | 16.76 ± 2.24 | 0.126 | 0.179§ |
Notes: *adjusted for age, gender, and AP severity using multivariable regression analysis; #using logistic regression; §using multiple linear regression.
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; CRP, C-reactive protein; WBC, white blood cell; PLT, platelet count; PT, prothrombin time; APTT, activated partial thromboplastin time; FIB, fibrinogen; TT, thrombin time.
Bonferroni-Corrected Post Hoc Comparisons
Post hoc pairwise comparisons with Bonferroni correction were performed for variables showing significant overall differences in the univariate analysis (Table 5). For CRP, significant differences were observed between liver and gallbladder dampness and heat and excess heat accumulation in the viscera groups (adjusted P < 0.05), while no significant differences were found in the remaining pairwise comparisons. For CRP, significant differences were identified between liver and gallbladder dampness and heat and liver depression and Qi stagnation, and between liver depression and Qi stagnation and excess heat accumulation in the viscera (adjusted P < 0.05), whereas the remaining comparison was not significant. For FIB, a significant difference was observed between liver and gallbladder dampness and heat and excess heat accumulation in the viscera (adjusted P < 0.05), while other pairwise comparisons were not significant. For TBIL, significant differences were found between liver and gallbladder dampness and heat and liver depression and Qi stagnation, and between liver depression and Qi stagnation and excess heat accumulation in the viscera (adjusted P < 0.05), while the remaining comparison was not significant. Overall, significant pairwise differences were observed only in specific group comparisons after Bonferroni correction.
Table 5.
Bonferroni-Corrected Post Hoc Comparisons of Significant Variables
| Variable | Statistical Test | Overall P Value | Pairwise Comparison | Bonferroni Adjusted P Value |
|---|---|---|---|---|
| CRP | Chi-square test | 0.010 | LGDH vs LDQS | <0.05 |
| LGDH vs EHAV | >0.05 | |||
| LDQS vs EHAV | <0.05 | |||
| FIB | One-way ANOVA | 0.022 | LGDH vs LDQS | 0.788 |
| LGDH vs EHAV | <0.05 | |||
| LDQS vs EHAV | 0.438 | |||
| TBIL | Chi-square test | 0.023 | LGDH vs LDQS | <0.05 |
| LGDH vs EHAV | >0.05 | |||
| LDQS vs EHAV | <0.05 |
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; CRP, C-reactive protein; FIB, fibrinogen; TBIL, total bilirubin.
Multivariable Regression Analysis Adjusted for Confounders
Multivariable regression analyses showed results broadly consistent with those of the univariate analysis. After adjusting for age, sex, and disease severity, statistically significant between-group differences were observed for CRP, FIB, and TBIL (P < 0.05) (Tables 2–4). For CRP, logistic regression analysis showed that, compared with liver and gallbladder dampness and heat, both liver depression and Qi stagnation (OR = 5.30, 95% CI: 1.73–16.19, P < 0.01) and excess heat accumulation in the viscera (OR = 3.68, 95% CI: 1.01–13.37, P < 0.05) were independently associated with higher odds of abnormal CRP levels (Table 6). For FIB, linear regression analysis showed that liver depression and Qi stagnation was significantly associated with higher FIB levels compared with liver and gallbladder dampness and heat (β = 1.34, 95% CI: 0.37–2.30, P < 0.01), whereas no significant difference was observed between excess heat accumulation in the viscera and liver and gallbladder dampness and heat (P > 0.05). For TBIL, logistic regression analysis indicated that liver depression and Qi stagnation had significantly higher odds compared with liver and gallbladder dampness and heat (OR = 4.32, 95% CI: 1.14–16.36, P < 0.05), while no significant difference was observed between excess heat accumulation in the viscera and liver and gallbladder dampness and heat (P > 0.05).
Table 6.
Multivariable-Adjusted Associations of AP Syndrome Groups with CRP, FIB, and TBIL
| Variable | Regression Model | Comparison | OR/β (95% CI) | P Value |
|---|---|---|---|---|
| CRP | Logistic regression | LDQS vs LGDH | 5.30 (1.73–16.19) | <0.01 |
| EHAV vs LGDH | 3.68 (1.01–13.37) | <0.05 | ||
| FIB | Linear regression | LDQS vs LGDH | 1.34 (0.37–2.30) | <0.01 |
| EHAV vs LGDH | 0.43 (−0.40–1.27) | 0.309 | ||
| TBIL | Logistic regression | LDQS vs LGDH | 4.32 (1.14–16.36) | <0.05 |
| EHAV vs LGDH | 1.86 (0.40–8.55) | 0.428 |
Abbreviations: LGDH, liver and gallbladder dampness and heat; LDQS, liver depression and Qi stagnation; EHAV, excess heat accumulation in the viscera; CRP, C-reactive protein; FIB, fibrinogen; TBIL, total bilirubin; OR, odds ratio; β, regression coefficient; CI, confidence interval.
Discussion
Recent interests have paid attention to the TCM syndrome of AP with an aim to identify the potential link between TCM syndrome and AP severity, however, there is a lack of high-quality studies.21 In this study, we analyzed the PEV, liver function and specific AP indices among AP patients with different TCM syndrome, with an aim to illustrate the potential link between TCM syndrome of AP and its severity. Our study for the first time showed that there were no statistical differences in the AP severity among patients with various TCM syndromes. Additionally, AP patients with different TCM syndromes showed differences in CRP, FIB, and TBIL. Overall, these findings are mainly descriptive and provide preliminary observational evidence on the relationship between TCM syndrome patterns and conventional clinical indicators in AP.
Recent Chinese consensus on AP severity has divided AP into six TCM syndromes including syndrome of liver depression and Qi stagnation, syndrome of liver and gallbladder dampness and heat, syndrome of excess heat accumulation in the viscera, syndrome of chest binding and interior excess, syndrome of blood stasis binds, and syndrome of internal blockage and external collapse.8,12 Among the six types of syndromes, the majority was syndrome of liver and gallbladder dampness and heat, followed by syndrome of liver depression and Qi stagnation. It has been reported that the main pathogenesis of AP is Qi stagnation, heat accumulation, and blood accumulation.11 Qi stagnation and heat accumulation are the causes, and blood accumulation is the result, that is, blood accumulation syndrome will only appear when AP develops to a serious stage. In this study, the majority of AP patients showed a syndrome of liver and gallbladder dampness and heat, followed by those with a syndrome of liver depression and Qi stagnation. Besides, our data showed that there were no statistical differences in the SAP among the three groups, which implied that the TCM syndrome may not show a link with the AP severity. In the future, multi-centered large sample sized studies are required to further illustrate their potential relationship.
AP is a common and relatively serious acute abdomen with a rapid onset and high mortality rate.22 It is difficult to differentiate AP from other acute abdominal diseases. Therefore, timely and accurate diagnosis of AP is particularly important, and in clinical settings, its diagnosis is mainly based on abdominal pain, nausea, and elevated serum α-AMY and LPS.23–25 In this study, we tried to illustrate the potential differences of AMY and LPS among AP patients with different TCM syndrome, and our results showed that there were no statistical differences in AMY and LPS among these patients. This suggested that serum AMY and LPS are not effective indicators for differentiating TCM syndromes in AP patients. Another important indicator, the PEV, has been confirmed to serve as a reliable radiologic biomarker in the prediction of severity and clinical outcomes of AP.20 In this study, there was no confirmed correction between PEV and TCM syndrome, and in the future, we will focus on expanding the sample size to further illustrate their potential link.
Most patients with AP develop varying degrees of liver injury during the disease course.26 In clinical practice, liver function is primarily evaluated using serum ALT, AST, TBIL, and ALB. Changes in these parameters also provide diagnostic value in distinguishing different types of liver injury associated with AP.27 Our data showed that TBIL may serve as an indicator for AP severity among patients with different TCM syndromes, while other indices such as DBIL, IDBIL, AST, ALT and ALB showed no differences among those with different TCM syndromes. In the present study, liver depression and Qi stagnation syndrome was independently associated with elevated TBIL compared with liver and gallbladder dampness-heat syndrome after adjustment for age, sex, and AP severity. This finding suggests that TCM syndrome patterns may reflect differences in hepatobiliary function that are not fully captured by conventional severity assessment. Although liver and gallbladder dampness-heat syndrome is traditionally considered closely related to biliary dysfunction, our results indicate that bilirubin abnormalities may also be prominent in patients with liver depression and Qi stagnation syndrome.16 One possible explanation is that impaired Qi movement in this syndrome may be accompanied by disturbances in bile flow and bilirubin metabolism, leading to higher odds of TBIL elevation.28
Regarding coagulation parameters, such as PT, APTT, FIB, and TT. We found that liver depression and Qi stagnation syndrome was independently associated with elevated FIB compared with liver and gallbladder dampness-heat syndrome. FIB is a key coagulation factor and acute-phase reactant involved in the interaction between inflammation and coagulation pathways.29,30 This finding indicates that patients with liver depression and Qi stagnation syndrome may exhibit a more pronounced procoagulant and inflammatory state than those with liver and gallbladder dampness-heat syndrome. From a TCM perspective, Qi stagnation reflects impaired Qi movement, which may predispose to the accumulation of pathological factors and subsequent blood stasis, potentially corresponding to enhanced activation of coagulation-related pathways in modern medicine.31
As a major acute-phase reactant, CRP is a widely recognized biomarker of systemic inflammation and reflects activation of proinflammatory pathways.32,33 We further found that both liver depression and Qi stagnation syndrome and excess heat accumulation in the viscera syndrome were independently associated with elevated CRP compared with liver and gallbladder dampness-heat syndrome. This finding suggests that these syndrome patterns may be associated with a more pronounced inflammatory response than liver and gallbladder dampness-heat syndrome. From a TCM perspective, liver depression and Qi stagnation may reflect impaired Qi movement with early transformation into heat, while excess heat accumulation in the viscera represents a more pronounced internal heat condition.12 These pathological states may correspond to enhanced activation of systemic inflammatory pathways and increased production of inflammatory mediators, resulting in higher CRP levels. Importantly, because no significant differences in AP severity were observed among syndrome groups, the associations of these biomarkers are more likely to reflect biological heterogeneity rather than differences in disease severity.
In clinical practice, AP caused by different etiologies often requires individualized diagnosis, treatment strategies, and prevention approaches. In this context, TCM syndrome classification may serve as a complementary stratification tool by linking symptom-based patterns with objective biochemical profiles, thereby supporting more individualized clinical management. Notably, CRP, FIB, and TBIL may have potential value as supportive indicators for identifying liver depression and Qi stagnation syndrome. However, these findings should be interpreted with caution due to the relatively small sample size and imbalance among syndrome groups. Further large-scale, prospective studies are required to validate these observations and confirm their clinical applicability.
There are some limitations in this study. First, the sample size was relatively small, with unequal numbers of patients across groups, which may have limited the statistical power of the study. Future studies with larger sample sizes are needed to further validate our findings. Second, in the multivariable regression models, only age, sex, and AP severity were adjusted for, while etiological factors were not included, which may introduce residual confounding. Future studies should incorporate etiology-stratified analyses. Third, although no statistically significant differences in AP severity were found among groups, the excess heat accumulation in the viscera group showed a higher proportion of SAP (33.33%) with a borderline P value (P = 0.204), suggesting a possible trend that may be limited by sample size and requires further validation. In addition, imaging assessment was limited to PEV, without using standardized scoring systems such as computed tomography severity index (CTSI) or Balthazar score, which may limit the robustness of imaging-syndrome correlation analyses.
Conclusions
In this two-center retrospective study, no significant differences in AP severity or imaging features were observed among TCM syndromes. Liver depression and Qi stagnation syndrome was associated with higher CRP, FIB, and TBIL compared with liver and gallbladder damp-heat syndrome. These findings suggest potential biological differences among syndromes. Overall, TCM syndrome classification remains exploratory, and the clinical relevance of these biomarkers requires further validation.
Funding Statement
This study was supported by the Shandong Provincial Traditional Chinese Medicine (TCM) Science and Technology Project (No. M-2023044) and Young Elite Sponsorship Program of Shandong Provincial Medical Association.
Data Sharing Statement
All data generated or analyzed during this study are included in this published article.
Ethics Approval and Informed Consent
This study was performed according to the convention of the Declaration of Helsinki, and the study protocols were approved by the Ethics Committee of the Guang’anmen Hospital (Approval No.: 2025-ky-030). Due to the retrospective nature of the study and the use of anonymized clinical data, the Ethics Committee formally waived the requirement for informed consent.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no competing interests in this work.
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Data Availability Statement
All data generated or analyzed during this study are included in this published article.