Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats.

OBJECTIVE: To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats. METHODS: Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. RESULTS: Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2α of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61±0.54 ng/mL, 0.42±0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31±0.24 ng/mL, 0.33±0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. CONCLUSION: AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.

Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats.

BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP.

Effect of electroacupuncture on the inflammatory response in patients with acute pancreatitis: an exploratory study.

OBJECTIVES: To examine the effects of electroacupuncture (EA) on inflammatory responses in patients with acute pancreatitis (AP). METHODS: Eighty patients with mild or severe AP were randomly allocated to a control group or an EA group. All patients were managed conservatively. In addition, the EA group received acupuncture for 30 min per day for 7 days at bilateral points ST36, LI4, TE6, ST37 and LR3. Interleukin (IL)-6, IL-10 and C-reactive protein (CRP) levels were measured on admission and on day 7. The time to re-feeding and length of stay in hospital were also recorded. RESULTS: A total of 58 patients provided complete data. The characteristics of the patients in the EA and control groups were similar. After 7 days the serum concentrations of IL-10 were higher in the EA group than in the control group (mild AP: 6.2±1.2 vs 5.2±0.9 pg/mL, p<0.05; severe AP: 14.9±7.8 vs 7.9±6.3 pg/mL, p<0.05). For patients with severe AP, the CRP level in the EA group was lower than in the control group (p<0.05). CONCLUSIONS: EA may reduce the severity of AP by inducing anti-inflammatory effects and reducing the time to re-feeding; however, it did not reduce the length of hospital stay. TRIAL REGISTRATION NUMBER: ChiCTR-TRC-13003572.

[Effects of electro-acupuncture at Zusanli point on gastric and intestinal blood flow in rats with acute necrotizing pancreatitis].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) at Zusanli point on gastric and intestinal blood flow and serum endothelin-1(ET-1), nitricoxide(NO), thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) in rats with acute necrotizing pancreatitis (ANP). METHODS: Thirty-six male Sprague Dawley (SD) rats were randomly divided into sham operation (sham), ANP and EA groups (n = 12). ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreaticobiliary. EA was applied to Zusanli for 30 min at 2 h and 6 h after the operation in EA group. Gastric and intestinal mucosal blood flow was measured by laser doppler flowmetry (LDF) at 12 h and 24 h after operation, while the levels of serum ET-1, NO, TXB2 and 6-K-PGF1alpha were detected. RESULTS: The gastric and intestinal blood flow in ANP rats were significantly lower than those in the sham group (P < 0.05), but those of EA groups were higher than those in ANP groups (P < 0.05). The serum ET-1, NO and ET-1/NO levels in ANP group were increased when compared with SO group (P < 0.05). After the electro-acupuncture treatment at Zusanli point, the levels of ET-1, NO and ET-1/N were decreased, and there were significant differences of ET-1 (at 12 h, 24 h), NO (at 12 h) and ET-1/NO (at 24 h) between EA and ANP group (P < 0.05). The levels of serum TXB2, 6-K-PGF1alpha and TXB2/6-K-PGF1alpha in ANP group were also increased (P < 0.05), but those in EA group were decreased, and there were significant differences of TXB2 (at 12 h, 24 h), 6-K-PGF1alpha (at 12 h) and TXB2/6-K-PGF1alpha (at 24 h) compared with ANP groups (P < 0.05). CONCLUSION: Electro-acupuncture at Zusanli point can significantly improve the gastric and intestinal mucosa blood flow in ANP rats, which may be related to the regulation of serum ET-1, NO, TXB2, 6-K-PGF1alpha.

Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment Liu-He-Dan in anaesthetized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal preparation of Liu-He-Dan ointment has been adapted for acute pancreatitis in external application for many years in West China. AIM OF THE STUDY: To investigate the effect of acute pancreatitis on the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally on belly. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were randomly divided into acute pancreatitis model group (n=6) and normal group as a control (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin, rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h) were detected and quantified by liquid chromatography-tandem mass spectrometry. Amylase in plasma were determined with iodide process. RESULTS: Among the five components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected in plasma and pancreas. The absorption of each component was tended to decrease in acute pancreatitis group after topically management with Liu-He-Dan ointment on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component were distinctly lower in AP group than those in normal group (p<0.05). However, the T(1/2α) and mean retention time (MRT) of emodin lasted longer in acute pancreatitis group than those in normal group (p<0.05). There was no statistical difference in the MRT of aloe emodin and physcion between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in acute pancreatitis model group than in normal group (0.91 ± 0.68, 0.41 ± 0.36, respectively). Physcion could be detected in pancreas of most acute pancreatitis models, but not in normal rats. Aloe emodin was found in all pancreas from acute pancreatitis models while only one in normal group. The level of amylase in Liu-He-Dan group was obviously lower than that in the AP model group (p=0.0055). CONCLUSION: We concluded that acute pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while external applied on belly, which indicated the dosage modification in AP. However, acute pancreatitis seems to promote the distribution of the detected components into pancreas. The ointment could help relieve the disease of pancreatitis.

Effect of formula compatibility on the pharmacokinetics of components from Dachengqi Decoction [See Text] in rats.

OBJECTIVE: To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, ) in rats. METHODS: Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study. RESULTS: The area under the curve (AUC), mean retention time (MRT), the peak concentration (C(max)) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C(max), and the absorption of Dahuang's component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang's component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C(max) and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T(1/2α)), the drug eliminated half-life time (T(1/2ß)), MRT, and time of peak concentration (T(max)) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer. CONCLUSIONS: The compatibility in Chinese medicine could affect the drug's pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.

[The influnence of dachengqi tang on acute lung injury and intra abdominal hypertension in rats with acute pancreatitis].

OBJECTIVE: To test the hypothesis "lung and large intestine are interior exteriorly related" through investgating into the effect of Dacheng qi tang (DCQT) on intra abdominal hypertension (IAH) and acute lung injury (ALI) in rats with acute pancreatitis. METHODS: Male SD rats were randomly divided into three groups with ten rats for each group: rats with sham-operations (SO); rats with acute necrosis pancreatitis (ANP); rats with ANP plus DCQT treatment. ANP was induced by retrograde infusion of 5% taurocholic acid into pancreatic duct. Two hours after operations, 10 mL/kg of normal saline was orally adminstered to the rats in both SO and ANP groups, whereas 10 mL/kg DCQT was adminstered to the rats in the treatment group. Aterial blood, pancreas and lung tissues were collected for biomarkers and histopathology 24 hours after operations. Intra-abdominal pressure and intestinal propulsion rate were also measured. RESULTS; DCQT treatment reduced intra-abdominal pressure and improved intestinal propulsion rate compared with those treated with saline (P < 0.05). The ANP rats treated with DCQT had lower wet to dry weight ratio, and milder myeloperoxidase activity and histopathology changes in pancreas and lung than those treated with saline (P < 0.05). Higher pressure of oxygen (PO2) was found in the rats treated with DCQT, while no difference in PCO2 was found between the DCQT and ANP groups (P > 0.05). Only two rats in the ANP group died. CONCLUSION: DCQT can effectively relieve IAH and cure ALI at the same time in rats with acute pancreatitis. The result provides evidence to support the hypothesis "lung and large intestine are interior exteriorly related".

Summary of integrative medicine for severe acute pancreatitis: 26-year clinical experiences and a report of 1 561 cases.

OBJECTIVE: To investigate the changing trends of clinical management for severe acute pancreatitis (SAP) with integrative medicine. METHODS: Clinical data of 1 561 patients with SAP from 1980 to 2005 was retrospectively analyzed. The mortality and morbidity of complications were compared. RESULTS: Of the 1 561 patients, 400 patients accepted surgical operation, while the rest were treated conservatively with integrative medicine. There was a change toward conservative management together with Chinese purgative herbal medication use after 1990 (22.4% from 1980-1990 compared with 45.5% from 1991-1993) because of high postoperative mortality. From 1994-2005, the treatment integrating Western medicine with Chinese herbal medications came to be preferred over the classic Western operation-based method. This change was associated with decreased morbidity (35.4% in 1980-1990 compared with 24.7% in 1991-1993 and 11.0% in 1994-2005, P<0.05) and lower mortality (40.52% of 1980-1990 compared with 17.17% of 1991-1993 and <10.25% of 1994-2005, P<0.05). CONCLUSION: The combination of conservative management with Chinese herbal medicines is preferable to classic Western medicine treatment to reduce morbidity and mortality of SAP, while surgery becomes a supplemental option.

Clinical observation on the effect of dexamethasone and Chinese herbal decoction for purgation in severe acute pancreatitis patients.

OBJECTIVE: To investigate the effect of dexamethasone (Dx) combined with modified Dachengqi Decoction (DCQD), a Chinese herbal decoction for purgation, on patients with severe acute on patients with severe acute, a Chinese herbal decoction for purgation, on patients with severe acute pancreatitis (SAP) accompanied with systematic inflammatory response syndrome (SIRS). METHODS: A total of 81 patients diagnosed as SAP were randomly assigned to a control group or treatment group according to a random number table generated from an SPSS software. The patients in the control group (38 cases) received standard treatment and Chinese herbal decoction for purgation; those in the treatment group (43 cases) received additional 1 mg/(kg·d) dexamethasone (Dx) treatment for three days based on the above treatment. The mortality rate, acute respiratory distress syndrome (ARDS), renal failure, hemorrhage, sepsis, pancreatic pseudocyst, pancreatic abscess, operability, and days of hospitalization were compared between the two groups. RESULTS: Three patients in the control group and eight patients in the treatment group dropped out from the study with a drop-out rate of 7.8% and 18.6%, respectively, and no statistics difference was shown between the two groups (P>0.05). Dx treatment significantly reduced ARDS rate and shortened the length of hospitalization compared to those in the control group (7/35, 20.0% versus 15/35, 42.9%, P=0.0394; 32.5±13.2 days versus 40.2±17.5 days, P=0.0344). Other parameters including the mortality rate were not significant different between the two groups. CONCLUSION: Dx combined with DCQD could decrease the risk of developing ARDS in SAP patients with SIRS and shorten their length of hospitalization.

Effect of severe acute pancreatitis on pharmacokinetics of Da-Cheng-Qi Decoction components.

AIM: To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats. METHODS: Rats were divided into SAP group and sham-operation group as a control group (n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics. RESULTS: Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The C(max) (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T(1/2alpha) of chrysophanol and rheochrysidin (P = 0.0467 and 0.0005, respectively) and T(max) of chrysophanol and rheochrysidin (P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group. CONCLUSION: SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.

Simultaneous determination and pharmacokinetic studies of aloe emodin and chrysophanol in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography.

A validated high-performance liquid chromatography (HPLC) method was developed for simultaneous determination and pharmacokinetic study of aloe emodin and chrysophanol in rats. It was performed on a reverse-phase C(18) column and a mobile phase made up of methanol and 0.2% acetic acid (83:17, v/v). The ultraviolet detection was 254 nm. 1,8-dihydroxyanthraquinone was used as the internal standard. The assay was linear over the range 28-2800 ng/mL (r(2) = 0.9993) for aloe emodin and 25.6-2560 ng/mL (r(2) = 0.9991) for chrysophanol. The average percentage recoveries of three spiked plasmas were 98.8-104.8% and 97.7-103.2% for aloe emodin and chrysophanol, respectively. Their RSD of intra-day and inter-day precision at concentrations of 56, 280 and 1400 ng/mL for aloe emodin and 51.6, 258 and 1290 ng/mL for chrysophanol were less than 3.5%. This method was applied for the first time to simultaneously determinate aloe emodin and chrysophanol in rats following oral administration of traditional Chinese medicine of Da-Cheng-Qi decoction. The pharmacokinetic parameters showed that chrysophanol was better absorbed with higher concentrations in plasma than aloe emodin did. They both eliminated slowly in male rats. The assay is suitable for identifying the plasma and tissue levels of aloe emodin and chrysophanol in preclinical investigations.

[A randomized controlled trial of Yiqi Pingchuan Granule in treating acute attack of bronchial spasm due to asthma of qi deficiency and cold syndrome].

OBJECTIVE: To evaluate the safety and efficacy of Yiqi Pingchuan Granule in treating acute attack of asthma due to qi deficiency and cold syndrome. METHODS: A randomized controlled trial was conducted. A total of 80 patients with an acute attack of asthma were included. They were allocated into two groups randomly in a ratio of three to one. Sixty patients in the treatment group received Yiqi Pingchuan Granule and 20 patients in the control group received Ruyi Dingchuan Pill. Patients in both groups were treated for 7 days. RESULTS: There were no significant differences in traditional Chinese medicine syndrome, clinical symptoms and lung function between the two groups (P>0.05). After treatment, the forced expiratory volume in 1 second was increased in the treatment group (P<0.05), and the peak expiratory flow was accelerated in the control group (P<0.05). No significant side effects were noted in both groups. CONCLUSION: Yiqi Pingchuan Granule is safe and effective in treating acute attack of asthma due to qi deficiency and cold syndrome.

[Randomized controlled trial on haiguiyuyang capsule in the treatment of duodenal ulcer].

OBJECTIVE: To assess the efficacy and safety of haiguiyuyang capsule in the treatment of duodenal ulcer (also diagnosed as weiwan pain and hanrecuoza syndrome according to the theory of TCM). METHODS: This is a multi-center clinical trial cooperatively conducted from May 2003 to March 2004 in accordance to the principle of informed consent, to the criteria for subject inclusion, exclusion, discontinuation, and to the relevant guidelines for evaluating the therapeutic effects of new TCM drugs. The design of double-blind, double-dummy and randomized controlled trial was adopted. 438 patients were randomized to the Test group (n = 330, treated with haiguiyuyang capsule) and to the Control group (n = 108, treated with ranitidine). The therapeutic course for both groups was 6 weeks. RESULTS: Regarding the efficacy in treating duodenal ulcer, in the Test group, the Marked Efficacy Rate was 66.37% and the Total Efficacy Rate was 82.13%; in the Control group, the Marked Efficacy Rate was 68.61% and the Total Efficacy Rate was 93.34%; there was no significant difference between the two groups (P>0.05). Regarding the efficacy in treating the syndrome diagnosed by TCM, in the Test group, the Marked Efficacy Rate was 70.31% and the Total Efficacy Rate was 93.34%; in the control group, the rates were 71.29% and 91.66% respectively; there was no significant difference between the two groups (P>0.05). Besides, regarding the abatement of distention and fullness of stomach after treatment, the haiguiyuyang capsule was better than ranitidine (P<0.05). No adverse side-effect was observed. CONCLUSION: The efficacy of haiguiyuyang capsule in treating duodenal ulcer is similar to that of ranitidine. No obvious adverse effect of it was observed in this trial.

[Immuno-modulatory effect of somatostatin combined with traditional Chinese medicine on severe acute pancreatitis at early stage: a randomized control trial].

OBJECTIVE: To evaluate the immuno-modulatory effect of short course administration of somatostatin (stilamin) continuously at early stage in patients with severe acute pancreatitis (SAP). METHODS: Thirty-nine patients with SAP (22 men, 17 women; the middle age was 49 years)were randomly allocated into control group (20 patients treated with non-surgical integrated traditional Chinese and Western medicine) and treatment group (19 patients treated with somatostatin administered intravenously at a dosage of 250 mug/h for consecutive 72 hours as well as the treatment for the control group). Laboratory parameters, including the expressions of CD(3), CD(4) and CD(8) in lymphocytes (tested by flow cytometry) and C reactive protein (CRP), and indexes of therapeutic effect, including the occurrence of organic dysfunction, local complication and mortality between the two groups were compared. Another group of 30 healthy volunteers (19 men, 11 women; the middle age was 47 years) were recruited for testing the normal levels of CD(3), CD(4) and CD(8). RESULTS: (1) The levels of CD(3), CD(4) and CD(4)/CD(8) in lymphocytes before treatment in both groups were significantly lower than those in the healthy subjects (P<0.05), but there were no statistical differences between the two groups. At the 4th day, CD(3), CD(4) and CD(4)/CD(8) increased significantly in the treatment group (P<0.05) while no changes in the control group; the levels of CD(4) and CD(4)/CD(8) in the treatment group were also higher than those in the control group (P<0.05). (2) The CRP levels of the 2 groups showed no statistical difference before and 4 days after the treatment, but the CRP level in the treatment group was significantly lower than that in the control group at the 7th day (P<0.05). WBC count, serum levels of amylase, lipase, lactate dehydrogenase, aspartate aminotransferase, as well as the score of APACHE II in the treatment group recovered more quickly than those in the control group (P<0.05). (3) The occurrences of organic dysfunctions, local complications and mortality in both groups were not statistically different. CONCLUSION: The short course administration of somatostatin continuously at early stage can reduce the inflammatory response, up-regulate the cell immune function and improve the conditions of the patients with SAP, but its effect on mortality and morbidity needs further study.

[Clinical study on the treatment of severe acute pancreatitis by integrated traditional Chinese medicine and Western medicine].

OBJECTIVE: To sum up clinical experiences and formulate a new treatment program for the effective managment of severe acute pancreatitis(SAP) by integrated TCM and western medicine. METHODS: The therapeutic regimens and end results of 1376 cases of SAP in three periods were reviewed and analyzed. Period I (1980-1990) was characterized by early surgical intervention supplemented with integrated traditional Chinese and western medical therapy, period II (1991-1993) by integrated traditional Chinese and western medical therapy supplemented with surgery for early complications, and period III (1994-2003) by integrated traditional Chinese and western medical therapy supplemented with surgery for local infectious complications at a late stage in the course of disease. RESULTS: With use of integrated traditional Chinese and western medical therapy in the treatment of SAP, the proportion of surgical operation and the case-fatality rate kept declining in the three consecutive periods, the proportions of operation being 77.59%, 54.54% and 19.38%, and the case-fatality rates being 40.52%, 17.17% and 10.77%, respectively. CONCLUSION: Integrated TCM and western medicine is effective for most SAP cases, and surgery is indicated mainly for late complications such as necrotizing infection. Early surgery should be handled with more circumspection and strictness in most of the patients with SAP.