Abstract Objective: The objective of this study was to investigate the effects of Da-Cheng-Qi decoction (DCQD) on enteroparalysis and levels of the serum inflammatory cytokines C-C motif chemokine ligand 2 (CCL2) and interleukin-8 (IL-8) in patients with severe acute pancreatitis (SAP). Methods: A total of 48 patients diagnosed with SAP who hospitalized in First Affiliated Hospital of Henan Traditional Chinese Medicine University from May 1, 2016 to May 30, 2018 were randomly assigned to the control or treatment groups. Patients in the control group (n = 22) received conventional treatment and those in the treatment group (n = 26) received conventional treatment as well as additional DCQD for 10 days. The duration of abdominal pain and distension, the time when bowel sounds returned to normal, changes in the levels of serum amylase, lipase, C-reactive protein (CRP), CCL2 and IL-8, as well as acute physiology and chronic health evaluation (APACHE) II scores of patients on days 1 and 10 were recorded and compared. Results: The duration of abdominal pain and distension, the time when bowel sounds returned to normal, the levels of blood amylase, lipase and CRP, and APACHE II scores of patients in the treatment group decreased significantly compared with those of patients in the control group. Though there were no statistical differences in serum CCL2 and IL-8 concentrations on day 1 between patients in these two groups, the levels of serum CCL2 and IL-8 in the treatment group were lower than those in the control group on day 10. Conclusion: DCQD may decrease the levels of CCL2, CRP, and IL-8 in patients with SAP, quickly relieve enteroparalysis, and shorten hospitalization duration.

1. ARTICLE
205
Submit a manuscript: https://www.tmrjournals.com/tmr
doi: 10.12032/TMR20190508119
TMR | July 2019 | vol. 4 | no. 4 |
Traditional Chinese Medicine
Effects of Da-Cheng-Qi decoction on enteroparalysis and serum
inflammatory cytokines in patients with severe acute pancreatitis
Xiao Wang1
*, Guo-Hong Yang1
, Chen-Xiao Wang1
, Chun-Ying Li1
, Min Guo1
, Ming-Hao Liu1
, Zhen-Jun
Zeng1
, Jun Ma2
, Qin-Sheng Zhang3
1
Department of Gastroenterology, First Affiliated Hospital of Henan Traditional Chinese Medicine University,
Zhengzhou, Henan, China. 2
Department of Gastroenterology, Second Affiliated Hospital of Zhengzhou University,
Zhengzhou, Henan, China. 3
Department of Gastroenterology, Henan Provincial Hospital of Traditional Chinese
Medicine, Zhengzhou, Henan, China.
*Corresponding to: Xiao Wang, Department of Gastroenterology, First Affiliated Hospital of Henan Traditional
Chinese Medicine University, 19 Renmin Road, Zhengzhou, Henan, China. E-mail: wangxiao1113@126.com.
Highlights
This study demonstrated that Chinese herbal formula Da-Cheng-Qi decoction combined with the
conventional treatment could effectively decrease the serum levels of CCL2, CRP, and IL-8, relieve
enteroparalysis, and shorten the duration of hospitalization in patients with severe acute pancreatitis.
Traditionality
Da-Cheng-Qi decoction (DCQD) is a famous Chinese herbal formula that includes Radix et Rhizoma Rhei
(Dahuang), Cortex Magnoliae Officinalis (Houpu), Fructus Aurantii Immaturus (Zhishi), and Natrii Sulfas
(Mangxiao). The original record about DCQD can be traced back to the 3rd Century A.D. According to the
description in Shanghan Lun, an ancient book of Chinese medicine published in Han Dynasty of China,
DCQD had the effect of purging accumulation and clearing heat from the stomach and intestine.

2. ARTICLE
206
Submit a manuscript: https://www.tmrjournals.com/tmr
doi: 10.12032/TMR20190508119
TMR | July 2019 | vol. 4 | no. 4 |
Abstract
Objective: The objective of this study was to investigate the effects of Da-Cheng-Qi decoction (DCQD) on
enteroparalysis and levels of the serum inflammatory cytokines C-C motif chemokine ligand 2 (CCL2) and
interleukin-8 (IL-8) in patients with severe acute pancreatitis (SAP). Methods: A total of 48 patients diagnosed
with SAP who hospitalized in First Affiliated Hospital of Henan Traditional Chinese Medicine University from
May 1, 2016 to May 30, 2018 were randomly assigned to the control or treatment groups. Patients in the control
group (n = 22) received conventional treatment and those in the treatment group (n = 26) received conventional
treatment as well as additional DCQD for 10 days. The duration of abdominal pain and distension, the time when
bowel sounds returned to normal, changes in the levels of serum amylase, lipase, C-reactive protein (CRP), CCL2
and IL-8, as well as acute physiology and chronic health evaluation (APACHE) II scores of patients on days 1 and
10 were recorded and compared. Results: The duration of abdominal pain and distension, the time when bowel
sounds returned to normal, the levels of blood amylase, lipase and CRP, and APACHE II scores of patients in the
treatment group decreased significantly compared with those of patients in the control group. Though there were no
statistical differences in serum CCL2 and IL-8 concentrations on day 1 between patients in these two groups, the
levels of serum CCL2 and IL-8 in the treatment group were lower than those in the control group on day 10.
Conclusion: DCQD may decrease the levels of CCL2, CRP, and IL-8 in patients with SAP, quickly relieve
enteroparalysis, and shorten hospitalization duration.
Keywords: Da-Cheng-Qi decoction, Severe acute pancreatitis, CRP, CCL2, IL-8
Acknowledgments:
This work was supported by Research Grant from Henan Provincial Administration of Traditional Chinese
Medicine (No.2016ZY2033), Funds for Creative Research Team of Henan Province, and Creative Research
Team of Chinese medicine research of Henan Province.
Abbreviations:
CCL2, C-C motif chemokine ligand 2; SAP, Severe acute pancreatitis; AP, Acute pancreatitis; SIRS, Systemic
inflammatory response syndrome; IL, Interleukin; ERCP, Endoscopic retrograde cholangiopancreatography;
DCQD, Da-Cheng-Qi decoction; TCM, Traditional Chinese medicine; TNF-α, Tumor necrosis factor-α;
APACHE II, Acute physiology and chronic health evaluation II; CRP, C-reactive protein; SD, Standard
deviation.
Competing interests:
All authors declare that they have no conflicts of interest.
Citation:
Xiao Wang, Guo-Hong Yang, Chen-Xiao Wang, et al. Effects of Da-Cheng-Qi decoction on enteroparalysis and
serum inflammatory cytokines in patients with severe acute pancreatitis. Traditional Medicine Research, 2019, 4
(4): 205-212..
Executive Editor: Cui-Hong Zhu, Submitted: 11 February 2019, Accepted: 13 May 2019, Online: 24 May 2019.

3. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 207
doi: 10.12032/TMR20190414115
Background
Severe acute pancreatitis (SAP) is a common acute
abdominal disease with rapid progression and high
mortality of 15-30% [1, 2]. Overall, 20-40% of patients
with acute pancreatitis (AP) die from multiple organ
failure induced by systemic inflammatory response
syndrome (SIRS) in the early stages [3].
Enteroparalysis is one of its severe complications.
Furthermore, enteroparalysis caused by SAP is an
important cause of SIRS and multiple organ
dysfunction syndrome [4]. The pathogenesis of
enteroparalysis in SAP is complex. The most studied
mechanisms include inflammatory factors,
gastrointestinal hormones, and pancreatitis-associated
ascites. Among these, inflammatory factors play an
important role in the development of enteroparalysis
[5].
Chemokines are a family of small (8-10 kDa)
inducible secreted cytokines with chemotactic and
activating effects on leukocyte subsets, and they play
key roles in the pathogenesis of SAP-associated
enteroparalysis [5]. Levels of proinflammatory
cytokines such as serum tumor necrosis factor-α
(TNF-α), interleukin (IL)-1β, IL-6, and IL-8 are
significantly higher in patients with SAP than in
patients with mild acute pancreatitis [6]. C-C motif
chemokine ligand 2 (CCL2), also known as monocyte
chemotactic protein-1, is a potent chemotactic for
monocytes that is produced constitutively or after
stimulation of various cell types. CCL2 provides
chemotactic cues for the recruitment of monocytes
from the bloodstream to the tissues [7-10]. It is an
early proinflammatory mediator that plays an
important role in SAP [11].
The effects of conventional treatments are
unsatisfactory and there is no specific therapy available
for SAP-associated enteroparalysis. Current Western
medical treatment strategies include intravenous fluid
resuscitation, prophylactic antibiotics, probiotics,
endoscopic retrograde cholangiopancreatography
(ERCP) in acute biliary pancreatitis [12] and
gastrointestinal motility therapy. Enteroparalysis is a
“bottleneck” in the current treatment of SAP.
Traditional Chinese medicine (TCM) has been used
for the treatment of SAP for a number of years.
Da-Cheng-Qi decoction (DCQD), a famous Chinese
herbal formula, is usually used for the treatment of
intestinal obstruction, acute cholecystitis, acute
appendicitis and AP. The components of DCQD
include Radix et Rhizoma Rhei (Dahuang), Cortex
Magnoliae Officinalis (Houpu), Fructus Aurantii
Immaturus (Zhishi), and Natrii Sulfas (Mangxiao).
Record about DCQD can be traced back to the 3rd
Century A.D. According to the description in
Shanghan Lun, an ancient book of Chinese medicine
published in Han Dynasty of China, DCQD had the
effect of purging accumulation and clearing heat from
the stomach and the intestines. Clinical study indicated
that the DCQD could improve symptoms of
postsurgical gastrointestinal dysfunction and was
beneficial to functional gastrointestinal disorders
patients [13, 14]. Studies using a rat model of
acute pancreatitis have shown that DCQD could
alleviate pancreatic, intestinal, and lung injury by
altering levels of IL-4, IL-6, IL-10 and TNF-α in AP
rats [15]. The study by Zhang YM, et al. showed
DCQD could alleviate liver damage by altering the
inflammatory response in rats with SAP [16]. But the
exact mechanisms of DCQD remains unclear. Thus,
the aim of the present study was to investigate the
effects of DCQD on enteroparalysis and levels of the
serum inflammatory cytokines CCL2 and IL-8 in
patients with SAP.
Materials and methods
Ethics statement
This study protocol (2015HL-043-01) was approved
by the Ethics Committee of the First Affiliated
Hospital of Henan Traditional Chinese Medicine
University (Zhengzhou, Henan, China), and all patients
provided written informed consent for the use of
clinical specimens for medical research.
Inclusion criteria
Male and female patients (18 to 65 years old) who
hospitalized within 24 h of the onset of SAP’s
symptoms were enrolled. The diagnostic criteria of
SAP follows revised Atlanta Classification [18].
Exclusion criteria
The following patients were excluded: patients with
pancreatic infection or peripancreatic infection caused
by another disease, patients sent directly to the
intensive care unit for multiorgan failure, post-ERCP,
or traumatic/operative pancreatitis, malignancy,
pregnancy, immunodeficiency, and patients in a
moribund state < 48 h before enrollment, regardless of
cause.
Withdrawal criteria
The following patients were withdrawn: patients were
unable to continuously receive TCM treatment; patient
strongly requested to withdraw from the study for
other reasons, patients died or received an operation
because they were unresponsive to intensive care
treatment within 72 h of admission.
Preparation of DCQD
Chinese medicinal herbs in DCQD were provided by
the First Affiliated Hospital of Henan Traditional
Chinese Medicine University (Zhengzhou, Henan,
China). Spray-dried DCQD powder comprised 20 g of

4. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 208
doi: 10.12032/TMR20190414115
Dahuang (Radix et rhizoma rhei), 30 g of Zhishi
(Fructus aurantii immaturus), 15 g of Houpu (Cortex
magnoliae officinalis), and 10 g of Mangxiao (Natrii
sulfas) (Chengdu Green Herbal Pharmaceutical Co.
Ltd, China). Every herb was made into a powder.
Before the experiment, DCQD powder was prepared as
a solution (200 mL).
Study design
This study was conducted at the First Affiliated
Hospital of Henan Traditional Chinese Medicine
University (Zhengzhou, Henan, China). Patients
enrolled in the study were randomly assigned to the
treatment or control groups using a random number
table generated by the software SPSS 17.0 (Chicago,
IL, USA). All enrolled patients were administered the
following standardized comprehensive medical
treatment: intensive care, oxygen inhalation,
gastrointestinal decompression, fluid resuscitation,
nutritional support, as well as treatment with proton
pump inhibitors and prophylactic antibiotics for 10
days. Patients in the treatment group received
additional DCQD via gastric perfusion (50 mL/2 h)
and retention enema (200 mL/3 h) for purgation for 10
days.
Indicators monitored
Patients were observed during their hospital stay.
Follow-up evaluations included duration of abdominal
pain and the time when abdominal
distension disappeared and normal bowel sounds
returned. Blood was collected from the elbow vein to
measure levels of CCL2, IL-8, amylase, lipase, and
C-reactive protein (CRP) using an MDI600 automatic
biochemical analyzer (Beckman, USA). These
parameters and acute physiology and chronic health
evaluation (APACHE) II scores [19] were recorded on
days 1 and 10. Serum CCL2 and IL-8 concentrations
(CCL2 and IL-8 antibodies were purchased from
Abcam, Cambridge, UK) were measured using
xxxxxxx
enzyme-linked immunosorbent assay (ELISA) kits
(Raybiotech, USA) according to the manufacturer’s
instructions.
Statistical analysis
Data are expressed as means ± standard deviation (SD)
and were analyzed using Student's t-test.
Non-parametric test was performed for non-normally
distributed samples. Statistical analyses were
conducted using SPSS 17.0 software. P < 0.05 was
considered to indicate statistically significant
differences.
Results
Clinical characteristics
A total of 56 patients with SAP who hospitalized in
First Affiliated Hospital of Henan Traditional Chinese
Medicine University from May 1, 2016 to May 30,
2018 were initially screened. 3 patients died and 4
patients received operation. 48 patients were enrolled
(26 in the treatment group and 22 in the control group).
No patient was withdrawn and no patient showed
verified evidence of adverse effects. There were no
statistical differences between the two groups with
regard to sex, age, etiology, APACHE II score, and
Balthazar computed tomography score in the initial
stage of hospitalization (P > 0.05, Table 1).
Effect of DCQD on enteroparalysis
No differences between the two groups with regard to
abdominal pain and abdominal distension on day 1 and
no bowel sounds were present in patients of either
group. After 10 days of hospitalization, the duration of
abdominal pain and distension and the time when
bowel sounds returned to normal were significantly
shorter in the treatment group than those in the control
group (P = 0.026, P = 0.031, P = 0.042, Table 2).
Table 1 Baseline data analysis
Baseline data
Control group
(n = 22)
Treatment group
(n = 26)
P
values
Sex (M/F)
Age (year)
Pathogen [(n)%] Cholelithiasis
Alcoholism
Hyperlipidemia
Idiopathic
APACHE II score (mean ± SD)
Balthazar CT score (mean ± SD)
12/10
48.5 ± 9.2
9 (40.9)
6 (27.3)
5 (22.7)
2 (9.1)
10.3 ± 5.6
4.8 ± 1.3
14/12
49.4 ± 8.9
10 (38.5)
8 (30.8)
6 (23.1)
2 (7.7)
9.9 ± 5.2
4.7 ± 1.5
0.234
0.215
0.752
0.702
0.728
0.510
0.262
0.257
M/F, Male/female; SD, Standard deviation.

5. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 209
doi: 10.12032/TMR20190414115
Effects of DCQD on APACHE II score and CRP
level
No significant differences in APACHE II scores and
serum CRP level between the treatment and the control
groups were observed on day 1. However, their
significantly decrease were present on day 10 (5.61 ±
1.08 of treatment group vs 7.00 ± 1.13 of control group,
P < 0.001, Figure 1A; 66.04 ± 13.94 of treatment
group vs 104.23 ± 21.61 of control group , P < 0.001,
Figure 1B).
Effects of DCQD on the levels of amylase and
lipase
Though there were no significant differences in the
levels of serum amylase and lipase between the
treatment and control groups on day 1. On day 10, the
levels of serum amylase and lipase in the treatment
group were lower than those in the control group
(80.46 ± 21.98 vs 137.41 ± 34.03, P < 0.001, Figure
2A; 193.27 ± 80.50 vs 335.23 ± 86.22, P < 0.001,
Figure 2B).
Table 2 The days of abdominal pain, abdominal distension and bowel sounds return to normal
Clinical manifestation Control group
(n = 22)
Treatment group
(n = 26)
P
Abdominal pain
Abdominal distension
Bowel sounds return
5.45 ± 2.27
5.12 ± 2.41
5.15 ± 2.17
3.81 ± 1.94
3.79 ± 1.93
3.67 ± 1.86
0.026
0.031
0.042
Figure 1 Effects of DCQD on APACHE II score and CRP level
DCQD, Da-Cheng-Qi decoction; APACHE II, Acute physiology and chronic health evaluation II; CRP,
C-reactive protein.

6. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 210
doi: 10.12032/TMR20190414115
Figure 2 Effects of DCQD on the levels of amylase and lipase
DCQD, Da-Cheng-Qi decoction.
Figure 3 Effects of DCQD on the levels of CCL2 and IL-8
CCL2, C-C motif chemokine ligand 2; IL-8, Interleukin-8; DCQD, Da-Cheng-Qi decoction.

7. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 211
doi: 10.12032/TMR20190414115
Effects of DCQD on the levels of CCL2 and IL-8
There were no significant differences in the levels of
serum CCL2 and IL-8 between the treatment and
control groups on day 1. However, on day 10, the
levels of serum CCL2 and IL-8 in the treatment group
were lower than those in the control group (0.33 ± 0.15
vs 0.65 ± 0.52, P = 0.009, Figure 3A; 398.66 ± 97.95
vs 502.13 ± 95.98, P < 0.001, Figure 3B).
Discussion
SAP is a serious systemic disease with a mortality of
approximately 15-30%, and with high morbidity of
acute lung injury, acute kidney injury, and impairment
of intestinal motility [3]. Enteroparalysis is the
predominant clinical symptom in patients with SAP.
Abdominal pain, abdominal distension, and the lack of
bowel sounds are its main clinical characteristics.
DCQD is a commonly used herbal prescription in the
treatment of early-stage SAP in China. It can
effectively improve symptoms and reduce the
incidence of complications and mortality of patients
with SAP by protecting intestinal mucosal barrier and
organ function. This clinical study also showed that the
duration of abdominal pain and distension and the time
when normal bowel sounds returned were shorter in
the treatment group than those in the control group.
Inflammatory chemokines are important mediators
during SAP and are involved in the activation and
migration of leukocytes into the tissues. In SAP, the
local inflammatory process is amplified, and the
inflammation spreads via the circulation throughout
the body, resulting in a systemic inflammatory
response [20, 21].
This process is characterized by the release of pro-
and anti-inflammatory cytokines and other
inflammatory mediators, which recruit neutrophils,
monocytes, and lymphocytes to the pancreas. CCL2 is
a chemotactic molecule for monocytes/macrophages, B
cells and T lymphocytes and belongs to the CC
subfamily of chemokines. It is an early
proinflammatory mediator that plays an important role
in SAP. Our data showed that CCL2 production
decreased after DCQD treatment. IL-8 is the most
thoroughly characterized member of the chemokine
family studied in AP. It is a powerful secondary
chemoattractant of neutrophils in the inflammatory
process [22]. A previous study indicated that changes
in serum CCL2 and IL-8 levels in patients with AP
follow a pattern, thus allowing the determination of
reference values for the diagnosis and evaluation of the
severity of AP [23].
In this study, we also observed that serum IL-8
levels in the treatment group were lower than those in
the control group. This indicates that DCQD may
inhibit the production of proinflammatory chemokines,
thereby preventing the pathological progress of SAP.
Furthermore, we noticed that DCQD treatment
improved APACHE II scores, which is the traditional
multifactorial scoring system used to predict the
severity of AP. Currently, CRP is the most frequently
used single biomarker to assess the severity of AP, as it
is inexpensive, widely available, and easy to measure.
We also noticed that DCQD treatment significantly
reduced serum CRP level. Moreover, DCQD treatment
decreased the levels of serum amylase and lipase.
These data indicate that DCQD may effectively
improve parameters used in the prognostic evaluation
of SAP.
Conclusion
The occurrence and development of SAP are closely
related to various inflammatory mediators and
cytokines. The action of inflammatory factors that may
damage the body may worsen the condition of SAP.
Therefore, the key to SAP treatment is to reduce the
inflammatory response, control the release of
inflammatory transmitters, and alleviate multiple organ
damage. This study demonstrated that DCQD
treatment decreased the levels of CCL2, CRP, and IL-8
in patients with SAP, effectively relieved
enteroparalysis, and shortened the duration of
hospitalization. The specific mechanisms of DCQD
involved in the treatment of SAP require further study.
References
1. Navarro S. Historical review of our knowledge
of acute pancreatitis. Gastroenterol Hepatol 2018,
41: 143.e1-143.e10.
2. Shah AP, Mourad MM, Bramhall SR. Acute
pancreatitis: current perspectives on diagnosis and
management. J Inflamm Res 2018, 11: 77-85.
3. Schietroma M, Pessia B, Carlei F, et al. Intestinal
permeability and systemic endotoxemia in
patients with acute pancreatitis. Ann Ital Chir
2016, 87: 138-144.
4. Jha RK, Ma Q, Sha H, et al. Emerging role of
resveratrol in the treatment of severe acute
pancreatitis. Front Biosci 2010, 2: 168-175.
5. Xiong B, Zhang JF, Zhang XG. Research
progress in the mechanism of severe acute
pancreatitis complicated with intestinal dynamic
disorders. Med Recapitulat 2018, 24: 226-230.
(Chinese)
6. Sakorafas GH, Tsiotou AG. Etiology and
pathogenesis of acute pancreatitis: current
concepts. J Clin Gastroenterol 2000, 30: 343-356.
7. Behfar S, Hassanshahi G, Nazari A, et al. A brief
look at the role of monocyte chemoattractant
protein-1 (CCL2) in the pathophysiology of
psoriasis. Cytokine 2018, 110: 226-231.
8. Leighton SP, Nerurkar L, Krishnadas R, et al.
Chemokines in depression in health and in
inflammatory illness: a systematic review and

8. ARTICLE
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | July 2019 | vol. 4 | no. 4 | 212
doi: 10.12032/TMR20190414115
meta-analysis. Mol Psychiatry 2018, 23: 48-58.
9. Yoshimura T. The chemokine MCP-1 (CCL2) in
the host interaction with cancer: a foe or ally?
Cell Mol Immunol 2018, 15: 335-345.
10. Siddiqui JA, Partridge NC. CCL2/Monocyte
chemoattractant protein 1 and parathyroid
hormone action on bone. Front Endocrinol 2017,
8: 49.
11. Evans AC, Papachristou GI, Whitcomb DC.
Obesity and the risk of severe acute pancreatitis.
Minerva Gastroenterol Dietol 2010, 56:
169-179.
12. Mandalia A, Wamsteker EJ, DiMagno M.
Recent advances in understanding and
managing acute pancreatitis. F1000 Research
2018, 7: 959.
13. Jin W, Li QJ, Luo XQ, et al.
Da-Cheng-Qi decoction combined with
conventional treatment for treating postsurgical
gastrointestinal dysfunction. Evid Based
Complement Alternat Med 2017, 1987396.
14. Zhao JL, Zhong CJ, He ZY, et al. Effect
of da-cheng-qi decoction on pancreatitis-
associated intestinal dysmotility in patients and in
rat models. Evid Based Complement Alternat
Med 2015, 895717.
15. Zhao XL, Zhang YM, Li J, et al. Tissue
pharmacology of Da-Cheng-Qi decoction in
experimental acute pancreatitis in rats. Evid
Based Complement Alternat Med 2015, 283175.
16. Zhang YM, Ren HY, Zhao XL, et al.
Pharmacokinetics and pharmacodynamics
of Da-Cheng-Qi decoction in the liver of rats with
severe acute pancreatitis. World J Gastroenterol
2017, 23: 1367-1374.
17. Kun Wu. Yi Fang Kao, People's Health
Publishing House, 2007.
18. Banks PA, Bollen TL, Dervenis C, et al. Acute
pancreatitis classification working group:
classification of acute pancreatitis-2012: revision
of the atlanta classification and definitions by
international consensus. Gut 2013, 62: 102-111.
19. Greenberg JA, Hsu J, Bawazeer M, et al. Clinical
practice guideline: management of acute
pancreatitis. Can J Surg 2016, 59: 128-140.
20. Akinosoglou K, Gogos C. Immune-modulating
therapy in acute pancreatitis: Fact or fiction.
World J Gastroenterol 2014, 20: 15200-15215.
21. Zerem E. Treatment of severe acute pancreatitis
and its complications. World J Gastroenterol 2014,
20: 13879-13892.
22. Manohar M, Verma AK, Venkateshaiah SU, et al.
Pathogenic mechanisms of pancreatitis. World J
Gastrointest Pharmacol Ther 2017, 8: 10-25.
23. Yang YZ, Xiang Y, Chen M, et al. Clinical
significance of dynamic detection for serum
levels of MCP-1, TNF-α and IL-8 in patients
with acute pancreatitis. Asian Pac J Trop Med
2016, 9: 1111-1114.