[Effect of Zhizhu Pill on Gastric Smooth Muscle Contractile Response and Protein Expression of Growth Hormone Secretagogue Receptor in Functional Dyspepsia Rats].

OBJECTIVE: To study the therapeutic mechanism of Zhizhu Pill (ZP) for treating functional dyspepsia (FD) rats. METHODS: Totally 30 ten-day-old male rats were randomly divided into the normal control group (n =10) and the model group (n = 20). The FD rat model was induced using gastric administration of 0.1% iodoacetamide (IA) combined tail clamping. The model was evaluated when rats were 8-week old. Successfully modeled rats were randomly divided into the model group (n = 10) and the ZP group (n = 10). Rats in the normal group and the model group were administered with normal saline by gastrogavage, while those in the ZP group were administered with ZP Decoction (2 mL/100 g) by gastrogavage. All medication lasted for 7 successive days. The contractile activity in in vitro longitudinal gastric muscle was recorded using Power Lab biological signal collecting system. The expression of growth hormone secretagogue receptor (GHSR) in stomach of FD rats was detected using Western blot and immunohistochemistry (IHC). RESULTS: Compared with the normal group, average frequencies of gastric contraction and changing rates of amplitude obviously decreased in the model group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR decreased in the model group (P < 0.01). Compared with the model group, average frequencies of gastric contraction and changing rates of amplitude obviously increased in the ZP group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR increased in the ZP group (P < 0.01). CONCLUSION: ZP could promote the gastric motility in FD rats induced by gastric administration of IA combined tail clamping, and its mechanism might be related to up-regulating GHSR protein level.

[Treating non-alcoholic fatty liver disease patients of Gan stagnation Pi deficiency syndrome by tiaogan lidi recipe: a randomized controlled clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of tiaogan Lipi Recipe (TLR) in treating non-alcoholic fatty liver disease (NAFLD) patients of Gan stagnation Pi deficiency syndrome (GSP-DS). METHODS: A randomized, double blind, placebo-controlled clinical trial was performed. Totally 99 NAFLD patients of GSPDS were randomly allocated into two groups, 66 patients in the treatment group (treated with-TLR, one dose per day) and 33 patients in the control group (treated with placebos, one dose per day). The therapeutic course for all was 12 weeks. All patients received lifestyle interventions including moderate aerobic exercise, moderate caloric restriction, and dietary changes. Clinical symptoms, CT indices, liver functions and blood lipids were observed before and after treatment. RESULTS: After 12 weeks of treatment, the total score of clinical symptoms decreased in the two groups (P <0. 01), and it was lower in the treatment group than in the control group (P <0. 05). Liver/spleen CT ratio increased in the treatment group (P <0. 01), and it was higher in the treatment group than in the control group (P <0. 01). After treatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) all decreased in the treatment group (P <0. 05, P <0. 01), while levels of ALT decreased in the control group (P <0. 05). Besides, all the 3 levels mentioned above were lower in the treatment group than in the control group (P <0. 05). Levels of total cholesterol (CHO) and triglyceride (TG) decreased in the two groups (P <0. 05), and they were lower in the treatment group (P <0. 05). Total effective rates of TCM syndrome, abdominal CT, liver functions, and blood lipids were 79. 69% (51/64 cases), 54. 69% (35/64 cases), 67. 65% (23/34 cases), and 67. 39% (31/46 cases) in the treatment group, while they were 56. 25% (18/32 cases), 25. 00% (8/32 cases), 33. 33% (6/18 cases), and 55. 56% (10/18 cases) in the control group. All were superior in the treatment group (P <0.05, P <0.01, respectively). CONCLUSION: TLR combined with lifestyle intervention could safely and effectively improve clinical symptoms of NAFLD patients of GSPDS, elevate liver/spleen CT ratios, and play a role in liver protection, anti-inflammation, and lowering blood lipids.

[Study on the mechanism of action of total saponins of Panax notoginseng in ameliorating oxidative stress and insulin resistance in rats fed with high fat diet].

OBJECTIVE: To investigate whether total saponins of Panax notoginseng (tPNS) can ameliorate oxidative stress and insulin resistance (IR) in the high fat induced nonalcoholic fatty liver disease (NAFLD) rat model and to explore the relationship between oxidative stress and IR. METHODS: Totally 50 healthy rats were randomly divided into the normal control group (NC), the model group, the high dose tPNS group (at the daily dose of 160 mg/kg), the low dose tPNS group (at the daily dose of 80 mg/kg), and the bicyclol group (at the daily dose of 100 mg/kg), 10 in each group. Rats in the NC group were fed with standard forage. Those in the rest group were fed with high fat forage. Distilled water was given by gastrogavage to those in the NC group and the model group. Corresponding medication was performed for 4 weeks. Four weeks later Lee's index and body weight were measured. All rats were sacrificed to detect the wet weight of livers. Their sera was isolated and detected to calculate liver functions (serum ALT and AST levels). Levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitive index (ISI) and insulin resistance index (IRI) were calculated. Serum levels of TNF-alpha and malondialdehyde (MDA), contents of total superoxide dismutase (T-SOD), hydroxy radical level (-OH), and total antioxidant capacity (T-AOC) were measured. Pathological changes of livers was observed by HE staining of paraffin section. RESULTS: Compared with the NC group, rats' wet liver weight and Lee's index increased in the model group (P < 0.05), and results of light microscopy showed that obvious fatty degeneration occurred in livers. Compared with the model group, rats' wet liver weight and Lee's index, as well as ALT and AST could be obviously improved by tPNS and bicyclol (P < 0.05, P < 0.01). The fatty deposition of liver cells could also be alleviated. Compared with the NC group, serum levels of-OH, MDA, and TNF-alpha significantly increased, and activities of T-SOD and T-AOC decreased in the model group (P < 0.01), also accompanied with IR. Compared with the model group, concentrations of -OH, MDA, and TNF-alpha decreased after treated by tPNS (P < 0.05, P < 0.01), activities of T-SOD and T-AOC got recovered (P < 0.05, P < 0.01), and IR got obvious improvement (P < 0.01). CONCLUSION: The anti-oxidative stress effect and IR improving effect of tPNS might play partial roles in treating NAFLD.

[Jinghuaweikang capsules combined with triple therapy in the treatment of Helicobacter pylori associated gastritis and duodenal ulcer and analysis of antibiotic resistance: a multicenter, randomized, controlled, clinical study].

OBJECTIVE: To explore the efficacy of Jinghuaweikang capsules plus triple therapy (LACJ) in treatment of Helicobacter pylori (H. pylori) associated gastritis or duodenal ulcer, compare it with bismuth-containing quadruple therapy (LACB) and standard triple therapy (LAC) and analyze the antibiotic sensitivity of gastric mucosal H. pylori strains from the failed patients. METHODS: A total of 565 patients with H. pylori infection were recruited from 11 hospitals from January 2010 to June 2011. There were 336 males and 229 females. They underwent gastroendoscopy examination due to upper gastrointestinal symptoms and had never received H. pylori eradication therapies. Duodenal ulcer patients were divided randomly into LACJ therapy group, LACB therapy group and LAC therapy group while gastritis patients LACJ therapy group and LACB therapy group. Group LAC received lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg, twice a day, for 7 d (d1-7). Group LACJ: LAC therapy plus Jinghuaweikang, 3 capsules, twice a day, for 7 d (d1-7) then Jinghuaweikang, 3 capsules, twice a day, for 14 d (d8-21). Group LACB: LAC plus bismuth potassium citrate 220 mg, twice a day, for 7 d (d1-7) and then bismuth potassium citrate 220 mg, twice a day, for 14 d (d8-21). All duodenal ulcer patients received lansoprazole (30 mg, once a day) for 14 days after the first 7-day of treatment (d 8-21). At least 28 days after the end of treatment, all patients underwent (13)C urea breath test. Gastric mucosa was collected under endoscopy from the failed patients. The detection technique of gene chip was employed to detect antibiotics resistant gene from mucosa. RESULTS: The eradication rates of duodenal ulcer patients in groups LACJ, LACB and LAC were as follows: per-protocol (PP), 80.2% (77/96), 89.9% (89/99) and 72.2% (70/97) (P = 0.007), intention-to-treat (ITT), 78.6% (77/98), 88.1% (89/101) and 70.0% (70/100) (P = 0.007). No statistical differences existed between groups LACJ and LACB or LAC (all P > 0.05). But there were statistical differences between groups LACB and LAC (both P = 0.002). The eradication rates of PP and ITT of chronic gastritis patients in groups LACJ and LACB were as follows: 75.8% (97/128), 74.6% (97/130) vs 83.8% (109/130), 80.1% (109/136) (both P > 0.05). The symptomatic improvements of abdominal pain, burning and acid reflux of duodenal ulcer patients in group LACJ were higher than those in groups LACB and LAC. There were statistical differences between groups LACJ and LAC (all P < 0.05). The symptomatic improvements of bloating and belching for chronic gastritis patients in group LACJ were higher than those of group LACB. But no significant difference existed between two groups (all P > 0.05). Sixty samples of gastric mucosa were collected from the failed patients. The detection rates of antibiotic-resistant gene to clarithromycin and amoxicillin were 60.0% (36/36) and 18.3% (11/60) respectively. CONCLUSIONS: The efficacy of LACJ for the treatment of H. pylori infection patients is similar to LACB and superior to LAC. And the symptomatic improvement of patients is better than the other two regimens. The main cause of treatment failure is antibiotic resistance of H. pylori strains.

[The current state and prospect of Chinese medicine gastroenterology].

The progress and existent problems of Chinese medicine (CM) gastroenterology since the National Eleventh Five-Year Plan were discussed in this article in terms of theory innovation, formulation of clinical pathway and diagnosis-treatment consensus, efficacy assessment, formulation of efficacy assessment scale, advantage diseases, and exploration of the syndrome standardization, progress in science research, academic exchange, and the construction of study platform, and so on. Meanwhile, the development of CM gastroenterology was prospected in the following five aspects: to enhance the theory inheritance and innovation, the construction of discipline standardization; to establish scientific clinical efficacy assessment methods and the standard system; to expend treatment technologies and feature therapies; and to clarify the modern scientific connotation of CM theory and treatment.

[Effects of shugan jianpi recipe on the ion transport of diarrhea predominant irritable bowel syndrome rat colon mucosa induced by 5-HT].

OBJECTIVE: To investigate the mechanism of Shugan Jianpi Recipe (SJR) on the ion transportation of diarrhea predominant irritable bowel syndrome (IBS-D) colon mucosa induced by 5-HT. METHODS: Totally 36 male SD rats were randomly divided into three groups, i. e., the normal group, the model group, and the SJR group, 12 in each group. IBS-D Rat model was induced by intracolonic instillation of acetic acid and restraint stress. After successful modeling, normal saline was given to rats in the normal group and the model group, while SJR was given to those in the SJR group by gastrogavage for 14 days. The short circuit current (lsc) technology was used to measure 5-HT induced lsc changes of the colon mucosa under the actions of drugs and specific blocking agents. RESULTS: There was no difference in basal current (BC), the potential difference (PD), and transmembrane resistance (TR) of the distal colon among the 3 groups (all P > 0.05). The 5-HT induced short circuit current change (delta lsc) was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05). When 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS, 500 micromol/L), an Ca(+)-dependent Cl- channel blocker, was added from the epiphragm of the colonic mucosa, the 5-HT induced delta lsc was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05). When Na+ was substituted in the epiphragm solution (Na+ free) or amiloride (100 micromol/L) was added from the epiphragm of the colonic mucosa, an epithelial Na+ channel blocker, the 5-HT induced delta lsc was lower in the model group than in the normal group (P < 0.05), and it was higher in the SJR group than in the model group (P < 0.05). CONCLUSIONS: SJR could affect the transmembrane electrolyte transportation of IBS-D rat induced by 5-HT through regulating the secretion of Cl- and HCO3-. The effects might be achieved by the coordination of apical Cl- channel CFTR, basolateral Na(+)-K+ ATPase, sodium-potassium-chloride cotransporter, sodium-bicarbonate cotransporter, Cl-/HCO3- exchanger, as well as K+ channel.

[Clinical study of comprehensive treatment of Chinese medicine in treating ulcerative colitis based on two steps according to the stage of disease].

OBJECTIVE: To observe the clinical efficacy of comprehensive treatment of Chinese medicine in treating ulcerative colitis (UC) according to syndrome differentiation therapy and the stage of disease. METHODS: Fifty-three patients with mild or moderate, initial onset or relapsed active UC of large intestinal dampness-heat syndrome were randomly assigned to two groups, the treatment group (27 cases) and the control group (26 cases). The treatment group was treated with oral Qingchang Huashi Recipe (QHR) and external application of Guanchang Recipe (GR) in the active stage, oral administration of Fuzheng Qingchang Recipe in the remission stage. Symptomatic modification was performed according to the features of the symptoms. Patients in the control group were treated with oral Mesalazine enteric coated tablet (MSRT, 1.0 g, 4 times daily) in the active stage, oral administration of MSRT (0.5 g, three times daily) in the remission stage. The main clinical symptoms, Chinese medicine syndrome, induced remission rate, and changes of quality of life were observed on the 28th, 56th, and 84th day after treatment. RESULTS: After 84 days of treatment, the scores of the symptoms such as diarrhea, passing stool with pus and blood, and the abdominal pain in the treatment group were obviously improved when compared with before treatment (P < 0.05). The scores of the symptoms such as diarrhea, and passing stool with pus and blood in the treatment group were better than those in the control group (P < 0.05). After 28, 56, and 84 days of treatment, the clinical efficacy of Chinese syndromes were 77.78%, 77.78%, and 88. 89%, respectively, and the induced remission rates were 63.0%, 77.8%, and 88.9%, respectively in the treatment group, better than those in the control group of the same phase (P < 0.05). After 84 days of treatment, the scores of the quality of life, the general symptoms, the emotional capacity, and the social capacity, tc. in the treatment group and the control group were improved than before treatment (P < 0.05). Besides, the scores of the quality of life in the treatment group were superior to that in the control group (P < 0.05). CONCLUSIONS: Comprehensive treatment of Chinese medicine in treating ulcerative colitis based on two steps according to the stage of disease can effectively improve the main symptoms of UC patients, improve the Chinese syndromes, elevate the clinical remission rate and patients' quality of life. It showed favorable clinical efficacy.

Modified Xiaochaihu Decoction for gastroesophageal reflux disease: A randomized double-simulation controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the symptoms of GERD, but the effects of MXD on GERD manifestations and relapse prevention need to be further explained. Therefore, we performed a prospective, double-blind, and double-simulation study. AIM: To verify the efficacy of MXD for GERD and its effect on esophageal motility. METHODS: Using randomization, double-blinding, and a simulation design, 288 participants with GERD were randomized to the treatment group and control group and received herbs (MXD) plus omeprazole simulation and omeprazole plus herbs simulation, respectively, for 4 wk. The GERD-Q scale score and esophageal manometry were measured at baseline, after treatment, and at 1 mo and 3 mo follow-up visits when medication was complete to evaluate recurrence indicators. RESULTS: The GERD-Q scale score in both groups decreased significantly compared to those before treatment (P < 0.01). However, no significant difference was observed between the two groups (P > 0.05). Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing (more than 50%) improved in both groups from baseline (P < 0.01), especially in the treatment group (P < 0.05). The percentage of small intermittent contractions, large intermittent contractions, and increased pre-phase contractions in the treatment group significantly improved compared with baseline (P < 0.05) but did not improve in the control group (P > 0.05). There was no significant difference between the groups after treatment (P > 0.05). The percentage of weak esophageal contractility (distal contractile integral < 450 mmHg·s·cm), improved in both groups (P < 0.01), but no significant difference was observed between the groups after treatment (P > 0.05). The relapse rate in the treatment group was lower than that in the control group at the 1 mo (P < 0.01) and 3 mo follow-up (P < 0.05). CONCLUSION: MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD. The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.

[A multi-center randomized controlled trial on treatment of diarrhea-predominant irritable bowel syndrome by Chinese medicine syndrome-differentiation therapy].

OBJECTIVE: To verify the clinical efficacy of Chinese Medicine syndrome-differentiation therapy in treating diarrhea-predominant irritable bowel syndrome IBS-D. METHODS: With a blinded randomized controlled design adopted, 360 patients with IBS-D were randomly assigned to two groups, the treated group and the control group, they were treated with Chinese medicine and Pinaverium bromide for four weeks respectively. RESULTS: Comprehensive evaluation showed that the total effective rate in the treated group was higher than that in the control group significantly (93.8% vs 81.3%, P<0.01). Efficacy assessment on symptoms (by scoring) showed that the efficacy in the treated group was better than that in the control group in aspects of improving abdominal pain (86.1% vs 70.3%), defecation coziness (involving the frequency of defecation, incidence of tenesmus in the latest 10 days and Bristol typing of stool characters), living interfering, and total BSS score (P<0.05 or P<0.01). CONCLUSION: Chinese medicine syndrome-differentiation dependent therapy shows good efficacy in treating IBS-D.

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.

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 TCM therapy for invigorating Pi, soothing Gan, eliminating dampness and resolving blood stasis on the short-term quality of life in patients with diarrhea type irritable bowel syndrome].

OBJECTIVE: To observe the TCM therapy for invigorating Pi, soothing Gan, eliminating dampness and resolving blood stasis (TCM-T) on the short-term quality of life (stQOL) in patients with diarrhea type irritable bowel syndrome (IBS-D). METHODS: One hundred and twenty-five patients with IBS-D were assigned to 3 groups, Group A was treated with TCM-T; Group B treated with some selected Chinese patent drugs according to patients' syndrome types, such as Changweikang granule, Guben Yichang tablet, Bupi Yichang pill and Shenling Baizhu pill, Group C treated with Western medicines as Dicetel 50 mg, Oryzanol 10 mg, and Bifid triple viable 420 mg, 3 times daily by oral administration. The therapeutic course was 4 weeks for all. The stQOL was evaluated and compared by SF-36 scale before and after treatment. RESULTS: Comparison between groups on the scores for the 8 dimensions of SF-36 scale, i.e., physiological function (PF), role physical (RP), body pain (BP), global health (GH), vitality (VT), society function (SF), emotional effect (RE), and mental health (MH), showed no significant difference before treatment, but scores of all the 8 dimensions were improved significantly in Group A after treatment (P < 0.05), with scores of SF, BP, GH and MH superior to those in Group B (P < 0.05, P < 0.01), and scores of RP, GH, SF, RE, PF and MH superior to those in Group C (P < 0.05, P < 0.01). CONCLUSION: TCM-T has favorable effect in treating IBS-D, it could improve the stQOL of patients.

Effects of Hemp seed soft capsule on colonic ion transport in rats.

AIM: To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats. METHODS: Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d. The normal and constipation groups were treated with distilled water. After the treatment, the fecal wet weight and water content were measured. The basal short-circuit current (Isc) and resistance were measured by an Ussing Chamber. Besides the in vivo drug delivery experiment above, an in vitro drug application experiment was also conducted. The accumulative concentrations of HSSC (0.1 mg/mL, 0.5 mg/mL, 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 10.0 mg/mL and 25.0 mg/mL) were added to the normal isolated colonic mucosa and the Isc was recorded. Further, after the application of either ion (Cl- or HCO3-) substitution, ion channel-related inhibitor (N-phenylanthranilic acid, glybenclamide, 4,4-diisothiocyano-2,2-stilbenedisulfonic acid or bumetanide) or neural pathway inhibitor [tetrodotoxin (TTX), atropine, or hexamethonium], the Isc induced by HSSC was also measured. RESULTS: In the constipation group, the fecal wet weight and the water content were decreased in comparison with the normal group (P < 0.01). After the treatment with HSSC, the fecal wet weight and the water content in the HSSC group were increased, compared with the constipation group (P < 0.01). In the constipation group, the basal Isc was decreased and resistance was increased, in comparison with the normal group (P < 0.01). After the treatment with HSSC, the basal Isc was increased (P < 0.05) and resistance was decreased (P < 0.01) in the HSSC group compared with the constipation group. In the in vitro experiment, beginning with the concentration of 1.0 mg/mL, differences in Isc were found between the experimental mucosa (with HSSC added) and control mucosa. The Isc of experimental mucosa was higher than that of control mucosa under the same concentration (1.0 mg/mL, P < 0.05; 2.5-25 mg/mL, P < 0.01). After the Cl- or HCO3- removal and pretreated with different inhibitors (cAMP-dependent and Ca2+-dependent Cl- channels, Na+-K+-2Cl- cotransporter (NKCC), Na+-HCO3- cotransporter or Cl-/HCO3- exchanger inhibitor), there were differences between experimental mucosa and control mucosa; the Isc of experimental mucosa was lower than that of control mucosa under the same concentration (P < 0.05). Meanwhile, after pretreatment with neural pathway inhibitor (TTX, atropine, or hexamethonium), there were no differences between experimental mucosa and control mucosa under the same concentration (P > 0.05). CONCLUSION: HSSC ameliorates constipation by increasing colonic secretion, which is mediated via the coaction of cAMP-dependent and Ca2+-dependent Cl- channels, NKCC, Na+-HCO3- cotransporter or Cl-/HCO3- exchanger.

Regulating effect of TongXie-YaoFang on colonic epithelial secretion via Cl- and HCO3- channel.

AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats. METHODS: In a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, epithelial Na+ channel (ENaC), Ca2+-dependent Cl- channel (CACC), Na+-K+-2Cl- co-transporter (NKCC), and Na+-HCO3- co-transporter (NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System (AD Instruments International). RESULTS: Under basal conditions, the changes of short-circuit current (∆Isc, µA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group (70.86 µA/cm2 ± 12.32 µA/cm2, 67.67 µA/cm2 ± 11.68 µA/cm2vs 38.8 µA/cm2 ± 7.25 µA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 5-HT-induced ∆Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 µA/cm2 ± 13.15 µA/cm2vs 74.62 µA/cm2 ± 10.73 µA/cm2, 69.22 µA/cm2 ± 11.7 µA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride (44.69 µA/cm2 ± 12.58 µA/cm2vs 62.05 µA/cm2 ± 11.26 µA/cm2, 62.11 µA/cm2 ± 12.01 µA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride (DPC), 5-HT-induced ∆Isc did not significantly differ in three groups (42.28 µA/cm2 ± 10.61 µA/cm2vs 51.48 µA/cm2 ± 6.56 µA/cm2vs 47.75 µA/cm2 ± 7.99 µA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers. CONCLUSION: TXYF-formula can regulate the Cl- and HCO3- secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO3- exchanger, NBC and NKCC co-transporters.

Correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori infection and symptoms in patients with chronic gastritis.

AIM: To evaluate the correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori (H pylori) infection and symptoms or the assemblage of symptoms in cases with chronic gastritis. METHODS: Biopsy samples at the gastric antrum were obtained from 62 patients with chronic gastritis. CD4 and CD8 cell infiltration was evaluated by immunohistochemical assays on frozen sections of the biopsy samples. Fifteen symptoms referring to digestion-related activity and non-digestion related activity were observed. The correlation between lymphocyte infiltration and each symptom or symptom assemblage was analyzed by logistic regression and K-mean cluster methods. RESULTS: CD4 cell infiltrations in gastric mucosa were much more in patients with H. pylori infection, while CD8 cell infiltrations were similar in patients with or without H. pylori infection. Logistic regression analysis showed that the symptoms including heavy feeling in head or body (t = 2.563), and thirst (t = 2.478) were significantly related with CD4 cell infiltration in gastric mucosa (P<0.05), and cool limbs with aversion to cold were related with CD8 cell infiltration (t = 2.872, P<0.05). Further analysis showed that non-digestive related symptom assemblage could increase the predicted percentage of CD4 and CD8 cell infiltration in gastric mucosa, including lower CD4 infiltration by 12.5%, higher CD8 infiltration by 33.3%, and also non-H. pylori infection by 23.6%. K-means cluster analysis of all symptoms and CD4 and CD8 cell infiltration in gastric mucosa showed a similar tendency to increase the predicted percentage of CD4, CD8 cell infiltration and H. pylori infection. CONCLUSION: Based on correlation between the gastric mucosa lymphocyte infiltration, H. pylori infection and clinical symptoms, symptoms or symptomatic assemblages play an important role in making further classification of chronic gastritis, which might help find a more specific therapy for chronic gastritis.

Inhibitory effect of TongXie-YaoFang formula on colonic contraction in rats.

AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula and its underlying mechanisms. METHODS: A neonatal maternal separation plus restraint stress (NMS + RS) model of diarrhea-predominant irritable bowel syndrome was developed by subjecting male Sprague-Dawley rats to daily maternal separation from postnatal days 2 to 21 plus restraint stress from days 50 to 59. Rats were randomly divided into two groups (NMS + RS and TXYF formula), and rats with no handling or separation were used as normal controls. Starting from postnatal day 60, rats were administered TXYF formula (9.84 g/100 g body weight) orally twice daily for 14 consecutive days, while the normal and NMS + RS groups were given distilled water. The distinctions of movement index (MI, area under the curve of contraction intensity/min, mg/min) and contraction frequency (CF, number of contractions/min, times/min) of isolated colonic longitudinal smooth muscle strips (CLSMs) in the three groups before and after treatment were observed with a Power Lab system. Different inhibitors were applied, and then 10(-4) mol/L acetylcholine chloride (Ach) was added to CLSMs to induce muscle contraction. RESULTS: Before treatment, the MI of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (545.49 ± 73.66 mg/min vs 245.76 ± 34.44 mg/min and 551.09 ± 54.29 mg/min vs 245.76 ± 34.44 mg/min, P < 0.01, respectively). After treatment, the MI in the TXYF formula group was lower than that in the NMS + RS group (261.39 ± 38.59 mg/min vs 533.9 ± 61.63 mg/min, P < 0.01). In the same way, the CF of CLSMs in the NMS + RS and TXYF formula groups was similar and both higher than that in the normal group (3.42 ± 0.25 times/min and 3.31 ± 0.21 vs 1.1 ± 0.17 times/min, P < 0.01) before treatment. After treatment, the CF in the TXYF formula group was lower than that in the NMS + RS group (1.42 ± 0.87 times/min vs 3.11 ± 0.82 times/min, P < 0.01) and similar to that in the normal group (1.42 ± 0.87 times/min vs 1.09 ± 0.13 times/min). When 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride and 4-aminopyridine were added to the bath and equilibrated for 30 min, respectively, and 10(-4) mol/L Ach was added to CLSMs to induce muscle contraction, MI of the CLSMs in the TXYF formula group was lower than that in the normal group (666 ± 36.32 mg/min vs 747.77 ± 49.47 mg/min, and 686.53 ± 39.17 mg/min vs 750.45 ± 29.39 mg/min; P < 0.01, respectively). The MI of CLSMs in the TXYF formula group was lower than that in the normal group after treatment with nifedipine (689.48 ± 30.84 mg/min vs 741.65 ± 32.41 mg/min; P < 0.05). CONCLUSION: TXYF formula inhibits colon contraction in rats. This may be related to activation of specific potassium channels and inhibition of extracellular calcium internal flow.

Efficacy of Gastrosis No.1 compound on functional dyspepsia of spleen and stomach deficiency-cold syndrome: a multi-center, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To assess the efficacy and safety of Gastrosis No.1 compound in the treatment of functional dyspepsia with Spleen (Pi) and Stomach (Wei) deficiency-cold syndrome. METHODS: A randomized, double-blind, placebo-controlled trial was performed in 5 centers. Patients with functional dyspepsia (FD) of Spleen-deficiency and qi-stagnation syndrome (162 cases) were randomly assigned to groups given Chinese herbal medicine (CHM) Gastrosis No.1 compound or placebo in a 2:1 ratio. This trial included a 4-week treatment period and a 4-week follow-up period. The outcomes were the dyspepsia symptom scores (measured by total dyspepsia symptom scale and single dyspepsia symptom scale) and syndromes of traditional Chinese medicine score (measured by traditional Chinese medicine syndrome scale). The outcomes were noted at weeks 0, 4 and 8. RESULTS: Compared with patients in the placebo group, patients in the CHM group showed significant improvement in the dyspepsia symptom scores as rated by patients and investigators (P <0.01), and also showed improvement in syndromes of traditional Chinese medicine score (P <0.01). No serious adverse event was reported. Safety tests obtained after 4 weeks of treatment showed no abnormal values. CONCLUSION: CHM Gastrosis No.1 compound was effective and safe in the treatment of functional dyspepsia with Spleen and Stomach deficiency-cold syndrome.