Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D).@*METHODS@#A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated.@*RESULTS@#Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05).@*CONCLUSION@#Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Effect of Chaiqin Chengqi Decoction on cholecystokinin receptor 1-mediated signal transduction of pancreatic acinar cells in acute necrotizing pancreatitis rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chaiqin Chengqi Decoction (,CQCQD) on cholecystokinin receptor 1 (CCKR1)-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis (ANP).</p><p><b>METHODS</b>Twenty-seven Sprague-Dawley rats were randomized into three groups: the control group, the ANP group, and the CQCQD group (9 in each group). ANP rats were induced by two intraperitoneal injections of 8% L-arginine (pH=7.0, 4.4 g/kg) over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD (CQCQD group) or physiological saline (control and ANP groups) at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C (PLC) and inositol-1,4,5-triphosphate (IP3), and determination of fluorescence intensity (FI) as a measure of intracellular calcium ion concentration [Ca(2+)]i.</p><p><b>RESULTS</b>The pancreatic histopathological score (6.2 ± 1.1) and the levels of PLC (1,187.2 ± 228.2 μg/mL) and IP3 (872.2 ± 88.4 μg/mL) of acinar cells in the ANP group were higher than those in the control (2.8 ± 0.4, 682.5 ± 121.8 μg/mL, 518.4 ± 115.8 μg/mL) and the CQCQD (3.8 ± 0.8, 905.3 ± 78.5 μg/mL, 611.0 ± 42.5 μg/mL) groups (P<0.05). [Ca(2+)]i FI for the ANP group (34.8±27.0) was higher than that in the control (5.1 ± 2.2) and CQCQD (12.6 ± 2.5) groups (P<0.05). The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated (expression ratio=1.761; P=0.024) compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated (expression ratio=0.311; P=0.035) compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group (1.43 ± 0.17) was higher than those in the control (0.70 ± 0.15) and CQCQD (0.79 ± 0.11) groups (P<0.05).</p><p><b>CONCLUSIONS</b>Pancreatic acinar cell calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP.</p>

Chemical composition, mechanism of antibacterial action and antioxidant activity of leaf essential oil of Forsythia koreana deciduous shrub

OBJECTIVE@#To identify the chemical constituents of leaf essential oil of Forsythia koreana (F. koreana) and evaluate its effects on bacterial strains.@*METHODS@#The essential oil of leaf of F. koreana was extracted by using hydrodistillation process and the volatile components investigated with the help of gas chromatography coupled with mass spectrometry. The antibacterial study was carried out with the help of agar disc diffusion method, MIC, MBC and viable count. The mode of action was determined with help of potassium ion flux, cellular material release and scanning electron microscopy. The antioxidant activity was determined with the help of 2, 3-diphenyl-2-picrylhydrazyl method, nitric oxide scavenging activity and superoxide anion radical scavenging assay.@*RESULTS@#Total ten compounds were identified as trans-phytol (42.73%), cis-3-hexenol (12.95%), β-linalool (10.68%), trans-2-hexenal (8.86%), trans-2-hexenol (8.86%), myrcenol (3.86%), 4-vinylphenyl acetate (3.86%), (4Z)-4,6-heptadien-1-ol (3.18%), lemonol (2.73%) and benzeneacetaldehyde (2.27%) by gas chromatography coupled with mass spectrometry. The antibacterial study was demonstrated that leaf essential oil of F. koreana act against foodborne and other pathogenic bacteria. The mode of action revealed that this essential oil acted on the cytoplasmic membrane, resulting in loss of integrity and increased permeability. In addition, leaf essential oil of F. koreana was shown to be rich in linalool, which contributes to improved antioxidant activity.@*CONCLUSIONS@#These results show that leaf essential oil of F. koreana has great potential as a natural food preservative, antibacterial and antioxidant agent.

Chemical composition, mechanism of antibacterial action and antioxidant activity of leaf essential oil of Forsythia koreana deciduous shrub

Objective: To identify the chemical constituents of leaf essential oil of Forsythia koreana (F. koreana) and evaluate its effects on bacterial strains. Methods: The essential oil of leaf of F. koreana was extracted by using hydrodistillation process and the volatile components investigated with the help of gas chromatography coupled with mass spectrometry. The antibacterial study was carried out with the help of agar disc diffusion method, MIC, MBC and viable count. The mode of action was determined with help of potassium ion flux, cellular material release and scanning electron microscopy. The antioxidant activity was determined with the help of 2, 3-diphenyl-2-picrylhydrazyl method, nitric oxide scavenging activity and superoxide anion radical scavenging assay. Results: Total ten compounds were identified as trans-phytol (42.73%), cis-3-hexenol (12.95%), β-linalool (10.68%), trans-2-hexenal (8.86%), trans-2-hexenol (8.86%), myrcenol (3.86%), 4-vinylphenyl acetate (3.86%), (4Z)-4,6-heptadien-1-ol (3.18%), lemonol (2.73%) and benzeneacetaldehyde (2.27%) by gas chromatography coupled with mass spectrometry. The antibacterial study was demonstrated that leaf essential oil of F. koreana act against foodborne and other pathogenic bacteria. The mode of action revealed that this essential oil acted on the cytoplasmic membrane, resulting in loss of integrity and increased permeability. In addition, leaf essential oil of F. koreana was shown to be rich in linalool, which contributes to improved antioxidant activity. Conclusions: These results show that leaf essential oil of F. koreana has great potential as a natural food preservative, antibacterial and antioxidant agent.

Changes of neuronal acetylcholine receptor alpha 7 of peritoneal macrophage in experimental acute pancreatitis treated by Chaiqin Chengqi Decoction () / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate effect of Chaiqin Chengqi Decoction (, CQCQD) on changes of neuronal acetylcholine receptor alpha 7 (nAChRα7) of peritoneal macrophages in acute pancreatitis (AP).</p><p><b>METHODS</b>Eighteen Kunming mice were equally randomized into the control group, AP group and CQCQD treatment group. AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart, while control mice received saline injections. At 72 h after the first injection of L-arginine, mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times, whilst mice in the other two groups received the same amount of saline feeding. Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline. Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression. Serum was collected for detection of interleukin-6 (IL-6), IL-10 and acetylcholine (ACh) levels, and pancreas was for histopathology analysis.</p><p><b>RESULTS</b>The CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score (4.5±0.5 vs. 6.2±1.7, P<0.05) and the serum IL-6 levels (1228.3±419.2 pg/mL vs. 1589.6±337.3 pg/mL, P<0.05). The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group (P>0.05), but were significantly up-regulated after the CQCQD treatment (P<0.05). The serum ACh levels in the AP group were significantly lower than those in the control group (3.1±0.6 μg/mL vs 4.8±0.7 μg/mL P<0.05), but were significantly increased after the CQCQD treatment (5.6±1.5 μg/mL vs 3.1±0.6 μg/mL, P<0.05).</p><p><b>CONCLUSION</b>CQCQD is protective against L-arginine-induced AP through mechanisms involving nAChRα7 of peritoneal macrophages.</p>

The effect of Chaiqin Chengqi Decoction () on modulating serum matrix metalloproteinase 9 in patients with severe acute pancreatitis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chaiqin Chengqi Decoction (, CQCQD) on regulating serum matrix metalloproteinase 9 (MMP-9) in patients with severe acute pancreatitis (SAP).</p><p><b>METHODS</b>Thirty-five SAP patients hospitalized in West China Hospital from September 1, 2008 to February 28, 2009 were randomly assigned to two groups using a computer-derived random number sequence in a ratio of 1:1, treatment group (18 patients) and the placebo control group (17 patients). The patients in the treatment group were administered with CQCQD by gastric perfusion (50 mL/2 h) and retention enema (200 mL/6 h) for 7 days. The two groups had similar baseline information. The clinical indicators, including the initial Balthazar's computed tomography (CT) score, acute physiology and chronic health evaluation II (APACHE II) scores on 1st, 3rd, 5th and 7th day, incidences and durations of complications and the serum C-reactive protein (CRP), levels of MMP-9 on the 1st, 3rd, 5th and 7th day, were recorded and compared between the two groups.</p><p><b>RESULTS</b>The serum MMP-9, CRP and the APACHE II scores on the 3rd, 5th and 7th day in the treatment group were lower than those in the control group (P<0.05). The serum MMP-9 was positively correlated with the APACHE II score on the 1st day (r=0.430, P=0.01). The durations of acute respiratory distress syndrome (5.4±2.4 vs. 2.9±1.3), acute hepatitis (4.6±0.8 vs. 1.9±0.6) and acute heart failure (3.9±1.6 vs. 1.3±0.6, <0.05) in the control group were longer than those in the treatment group.</p><p><b>CONCLUSION</b>CQCQD could decrease the serum MMP-9 to relieve the severity of clinical symptoms and prevent the development of multiple organ dysfunction syndrome in patients with SAP.</p>

Effect of Chaiqinchengqi decoction on serum amyloid A in severe acute pancreatitis patients

OBJECTIVE@#To investigate the effect of Chaiqinchengqi decoction (CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis (SAP) patients.@*METHODS@#Thirty-five participants enrolled and were randomly assigned into either a treatment condition (n = 17, treated with CQCQD) or a control condition (n = 18, treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline. Upon admission, the Acute Physiology and Chronic Health Evaluation score II (APACHE II), SAA, serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured, as well as on the first, 3rd and 7th day and were compared between the two groups. Organ complications, infection, operation rate, mortality and hospital stay were also compared.@*RESULTS@#The duration of acute respiratory distress syndrome, acute hepatitis, acute renal failure, gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group (P < 0.05). The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group (P < 0.05) as well as length of hospital stay (P < 0.01). After 3 days of hospitalization, the APACHEII, score SAA levels, serum CRP and IL-6 in the treatment group was lower than those in the control group (P < 0.05). SAA was positively correlated with serum CRP (R = 0.346, P = 0.042), Ranson score (R = 0.442, P = 0.008) and serum IL-6 (R = 0.359, P = 0.034). The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis (PN) was 0.815 (95% CI: 0.625-0.954; P = 0.006). The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6% and specificity 68.2%.@*CONCLUSIONS@#The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.

Clinical study on treatment of severe acute pancreatitis by integrative Chinese and Western medicine combined with somatostatin / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study whether the therapeutic effect could be enhanced by combined use of somatostatin and conventional integrative Chinese and western medicine (TCM-WM) in treating severe acute pancreatitis (SAP).</p><p><b>METHODS</b>Sixty patients of SAP were randomly divided equally into the somatostatin group (Group A) and the baseline treated group (Group B), they were all treated with non-surgical TCM-WM treatment, but to Group A, the intravenous injection of somatostatin 250 micrograms/h for 72 hrs continuously was given additionally. Laboratory parameters, condition of disease and therapeutic effect indexes, including occurrence of organic dysfunction, local complication and mortality, between the two groups were compared.</p><p><b>RESULTS</b>The recovery of serum levels of amylase, lipase, C reaction protein, lactate dehydrogenase, aspartate aminotransferase, as well as the scores of APACHE II in Group A were quicker than those in Group B (P < 0.05). The occurrence of organic dysfunction and local complication in Group A were lower to those in Group B, but without statistic significance. Comparison of the mortality in the two groups showed insignificant difference (P > 0.05).</p><p><b>CONCLUSION</b>The early stage short course of combined TCM-WM and somatostatin treatment could improve the condition of SAP, but its effect on mortality should be further verified by enlarging the sample size.</p>