The herbal preparation, STW5-II, reduces proximal gastric tone and stimulates antral pressures in healthy humans.

BACKGROUND: The herbal preparation, STW5-II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5-II on esophago-gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut-brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. METHODS: STW5-II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double-blind, randomized fashion, on two separate occasions, separated by 3-7 days, to evaluate effects on (i) esophago-gastric junction pressures following a standardized meal using solid-state high-resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high-resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). KEY RESULTS: STW5-II increased maximum intrabag volume (ml; STW5-II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago-gastric junction, pyloric, or duodenal pressures. CONCLUSIONS & INFERENCES: STW5-II has marked region-specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia.

[Clinical study of evaluating the clinical effect of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area measured by bedside ultrasound].

OBJECTIVE: To evaluate the clinical value of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area (CSA) measured by bedside ultrasound. METHODS: A parallel group randomized controlled trial was conducted. A total of 80 patients with sepsis with gastrointestinal dysfunction admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2021 to October 2022 were enrolled. According to whether patients agree to use Dachengqi decoction after admission, all patients were divided into Dachengqi decoction group (observation group) and conventional treatment group (control group) by 1 : 1 randomization, each group has 40 patients. Both groups were treated with fluid resuscitation, anti-infection, maintaining stable respiratory circulation, early nourishing feeding, promoting gastrointestinal motility, and regulating intestinal flora. The observation group was treated with Dachengqi decoction on the basis of western medicine, 30 mL decoction was taken in the morning and evening. Both groups were treated for 7 days. The CSA of the two groups was measured by bedside ultrasound before and after treatment. The gastric residual volume (GRV1 and GRV2) were calculated by formula and traditional gastric tube withdrawal method. The gastrointestinal dysfunction score, acute physiology and chronic health evaluation II (APACHE II), intraperitoneal pressure (IAP), serum preprotein (PA), albumin (Alb), white blood cell count (WBC), procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP), length of intensive care unit (ICU) stay and incidence of aspiration were detected to evaluate the clinical efficacy of Dachengqi decoction, the correlation and advantages and disadvantages between CSA measured by bedside ultrasound and other evaluation indicators of gastrointestinal dysfunction in sepsis were also analyzed. RESULTS: There were no significant differences in the indicators before treatment between the two groups, which were comparable. In comparison with the pre-treatment period, CSA, GRV, gastrointestinal dysfunction score, APACHE II score, IAP, WBC, PCT, and hs-CRP of the two groups after treatment were significantly decreased, PA and Alb were significantly increased, and the observation group decreased or increased more significantly than the control group [CSA (cm2): 4.53±1.56 vs. 6.04±2.52, GRV1 (mL): 39.85±8.21 vs. 53.05±11.73, GRV2 (mL): 29.22±5.20 vs. 40.91±8.97, gastrointestinal dysfunction score: 0.87±0.19 vs. 1.35±0.26, APACHE II score: 11.54±3.43 vs. 14.28±3.07, IAP (cmH2O, 1 cmH2O ≈ 0.098 kPa): 9.79±2.01 vs. 13.30±2.73, WBC (×109/L): 9.35±1.24 vs. 12.35±1.36, PCT (µg/L): 3.68±1.12 vs. 6.43±1.45, hs-CRP (mg/L): 24.76±5.41 vs. 46.76±6.38, PA (mg/L): 370.29±45.89 vs. 258.33±34.58, Alb (g/L): 38.83±5.64 vs. 33.20±4.98, all P < 0.05]. The length of ICU stay (days: 10.56±3.19 vs. 14.24±3.45) and incidence of aspiration (12.5% vs. 25.0%) were lower than those in the control group (both P < 0.05). Correlation analysis showed that CSA measured by bedside ultrasound was positively correlated with GRV2, gastrointestinal dysfunction score, APACHE II score, and IAP (r values were 0.84, 0.78, 0.75, 0.72, all P < 0.01) and negatively correlated with PA and Alb (r values were -0.64 and -0.62, both P < 0.01). CONCLUSIONS: The Dachengqi decoction can significantly improve the clinical symptoms of septic patients with gastrointestinal dysfunction, reduce systemic inflammatory response, improve nutritional status, and shorten ICU hospital stay. Bedside ultrasound monitoring of CSA is a simple, accurate and effective means to evaluate gastrointestinal dysfunction, which is worthy of further clinical promotion.

Wei-Tong-Xin ameliorated cisplatin-induced mitophagy and apoptosis in gastric antral mucosa by activating the Nrf2/HO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wei-Tong-Xin (WTX) originated from the famous ancient Chinese formula "Wan Ying Yuan", recorded in the ancient Chinese medicine book "Zhong Zang Jing" by Hua Tuo. As "Jun" drugs, Dahuang and Muxiang have the effects of clearing heat and expelling fire, reducing food retention, regulating Qi and relieving pain. As "Chen" drug, Qianniuzi has the effect of assisting "Jun" drugs. Zhuyazao and Gancao, as "Zuo-Shi" drugs, can reduce toxicity and modulate the medicinal properties of other herbs. AIM OF THE STUDY: The present study aimed to investigate the effect and mechanism of WTX on the oxidative stress of gastric antrum mucosa in mice with cisplatin (CIS)-induced dyspepsia. MATERIALS: AND. METHODS: A variety of experimental methods, including western blot, qRT-PCR, immunofluorescence and immunohistochemistry were performed in vivo and in vitro. RESULTS: In vivo, WTX restored the number and function of interstitial cells of Cajal (ICCs), accompanied by the inhibition of lipid peroxidation. Moreover, WTX inhibited the activation of Parkin-dependent mitophagy and apoptosis. In vitro, WTX activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and inactivated mitophagy in GES-1 cells. To explore the role of Nrf2 in WTX's improvement of CIS-induced cell damage, Nrf2 inhibitor ML385 was used in cell experiments. We found that ML385 counteracted the regulation of WTX on mitophagy and apoptosis. Finally, N-acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, was applied in our experiments, and the results suggested that WTX suppressed the CIS-induced apoptosis via mitochondrial pathway. CONCLUSIONS: The above results, for the first time, indicated that WTX inhibited mitophagy and apoptosis of gastric antral mucosal cells induced by CIS through the Nrf2/HO-1 signaling pathway.

Clinical study of evaluating the clinical effect of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area measured by bedside ultrasound / 中华危重病急救医学

OBJECTIVE@#To evaluate the clinical value of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area (CSA) measured by bedside ultrasound.@*METHODS@#A parallel group randomized controlled trial was conducted. A total of 80 patients with sepsis with gastrointestinal dysfunction admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2021 to October 2022 were enrolled. According to whether patients agree to use Dachengqi decoction after admission, all patients were divided into Dachengqi decoction group (observation group) and conventional treatment group (control group) by 1 : 1 randomization, each group has 40 patients. Both groups were treated with fluid resuscitation, anti-infection, maintaining stable respiratory circulation, early nourishing feeding, promoting gastrointestinal motility, and regulating intestinal flora. The observation group was treated with Dachengqi decoction on the basis of western medicine, 30 mL decoction was taken in the morning and evening. Both groups were treated for 7 days. The CSA of the two groups was measured by bedside ultrasound before and after treatment. The gastric residual volume (GRV1 and GRV2) were calculated by formula and traditional gastric tube withdrawal method. The gastrointestinal dysfunction score, acute physiology and chronic health evaluation II (APACHE II), intraperitoneal pressure (IAP), serum preprotein (PA), albumin (Alb), white blood cell count (WBC), procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP), length of intensive care unit (ICU) stay and incidence of aspiration were detected to evaluate the clinical efficacy of Dachengqi decoction, the correlation and advantages and disadvantages between CSA measured by bedside ultrasound and other evaluation indicators of gastrointestinal dysfunction in sepsis were also analyzed.@*RESULTS@#There were no significant differences in the indicators before treatment between the two groups, which were comparable. In comparison with the pre-treatment period, CSA, GRV, gastrointestinal dysfunction score, APACHE II score, IAP, WBC, PCT, and hs-CRP of the two groups after treatment were significantly decreased, PA and Alb were significantly increased, and the observation group decreased or increased more significantly than the control group [CSA (cm2): 4.53±1.56 vs. 6.04±2.52, GRV1 (mL): 39.85±8.21 vs. 53.05±11.73, GRV2 (mL): 29.22±5.20 vs. 40.91±8.97, gastrointestinal dysfunction score: 0.87±0.19 vs. 1.35±0.26, APACHE II score: 11.54±3.43 vs. 14.28±3.07, IAP (cmH2O, 1 cmH2O ≈ 0.098 kPa): 9.79±2.01 vs. 13.30±2.73, WBC (×109/L): 9.35±1.24 vs. 12.35±1.36, PCT (μg/L): 3.68±1.12 vs. 6.43±1.45, hs-CRP (mg/L): 24.76±5.41 vs. 46.76±6.38, PA (mg/L): 370.29±45.89 vs. 258.33±34.58, Alb (g/L): 38.83±5.64 vs. 33.20±4.98, all P < 0.05]. The length of ICU stay (days: 10.56±3.19 vs. 14.24±3.45) and incidence of aspiration (12.5% vs. 25.0%) were lower than those in the control group (both P < 0.05). Correlation analysis showed that CSA measured by bedside ultrasound was positively correlated with GRV2, gastrointestinal dysfunction score, APACHE II score, and IAP (r values were 0.84, 0.78, 0.75, 0.72, all P < 0.01) and negatively correlated with PA and Alb (r values were -0.64 and -0.62, both P < 0.01).@*CONCLUSIONS@#The Dachengqi decoction can significantly improve the clinical symptoms of septic patients with gastrointestinal dysfunction, reduce systemic inflammatory response, improve nutritional status, and shorten ICU hospital stay. Bedside ultrasound monitoring of CSA is a simple, accurate and effective means to evaluate gastrointestinal dysfunction, which is worthy of further clinical promotion.

[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

Effects of Simo decoction on gastric motility of diabetic rats.

BACKGROUND: To investigate the effects of simo decoction (SMD) on the gastric motility of diabetic rats. METHODS: Diabetic rats were gavaged with various doses of SMD (0.15, 1.5, and 3.0 ml/kg/d) or saline, and their blood glucose levels and body weight were monitored. Gastric emptying and antral motility were assessed by phenol red retention and contractions of antral strips, respectively. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and neurogenic nitric oxide synthase (nNOS) in the gastric antrum were determined by real-time polymerase chain reaction and Western blot. RESULTS: Gastric emptying was delayed in diabetic rats (p < 0.01 vs. non-diabetic controls) but accelerated after SMD administration (p < 0.01). The contractions of antral strips were reduced in diabetic rats (p < 0.01 vs. non-diabetic controls) but improved after SMD intervention (p < 0.05). The mRNA expressions of SP, VIP, and nNOS in diabetic rats were downregulated compared with non-diabetic controls (all p < 0.01). Simo decoction treatment did not affect the expression of these factors in diabetic rats. The protein levels of SP, VIP, and nNOS in diabetic rats were decreased (p < 0.01), increased (p < 0.01), and comparable (p > 0.05), respectively, in comparison with non-diabetic controls. Simo decoction administration increased SP protein expression (p < 0.01) and decreased the levels of VIP (p < 0.01) and nNOS (p < 0.01) in diabetic rats. CONCLUSIONS: Simo decoction improved gastric dysmotility of diabetic rats possibly by upregulating SP and downregulating VIP and nNOS.

[Effect of electroacupuncture combined with Zhuang-medicine-thread moxibustion on expression of apoptosis-related factors in gastric antrum of diabetic gastroparesis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Zhuang-medicine-thread moxibustion on expression of apoptosis-related factors in gastric antrum of diabetic gastroparesis (DGP) rats, so as to explore its mechanism underlying improvement of DGP. METHODS: Male SD rats were randomly divided into normal, model, medication, EA, Zhuang-medicine-thread moxibustion (moxibustion) and EA+moxibustion (combination) groups (12 rats in each group). The DGP model was established by intraperitoneal injection of streptozotocin (STZ). Rats of the medication group were treated by gavage of 0.15 mg/mL mosapride citrate suspension （10 mL/kg）. EA (10 Hz/50 Hz, 2 mA, 20 min) or Zhuang-medicine-thread moxibustion (3 cones) was applied to "Zhongwan" (CV12), bilateral "Neiguan" (PC6) and bilateral "Sanyinjiao" (SP6) of the related groups, once a day for 3 weeks. The blood glucose, gastric emptying rate and intestinal propulsion rate of rats were measured. The apoptosis index of gastric antrum cells were observed by TUNEL staining. The protein and mRNA expressions of Caspase-3, B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in gastric antrum were detected by Wes-tern blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the blood glucose, the apoptosis index, the protein and gene expressions of Caspase-3 and Bax were significantly increased (P<0.01), and the gastric emptying rate, intestinal propulsive rate, the protein and gene expressions of Bcl-2 were considerably decreased (P<0.01) in the model group. In contrast to the model group, the blood glucose in the EA, moxibustion and combination groups, the apoptosis index in the 4 treatment groups, as well as Caspase-3 protein, Bax protein and mRNA expressions in the medication, EA and combination groups, Caspase-3 protein and mRNA, Bax mRNA expressions in the moxibustion group were significantly decreased (P<0.01, P<0.05); while the gastric emptying rate and intestinal propulsive rate in the 4 treatment groups, and Bcl-2 protein and mRNA expressions in the medication and combination groups, Bcl-2 mRNA expressions in the EA and moxibustion groups were obviously increased (P<0.01). The effects of EA+moxibustion were significantly superior to those of simple EA, moxibustion or medication in increasing gastric emptying rate and intestinal propulsive rate, and in lowering blood glucose (P<0.05, P<0.01). And the effects of the combination treatment were better than those of EA in lowering Caspase-3 protein and Bax mRNA expressions (P<0.01), and in increasing Bcl-2 protein and mRNA expressions (P<0.05, P<0.01). Also the effects of the combination treatment were better than those of moxibustion in lowering the apoptosis index, Caspase-3 protein, and Bax protein and mRNA expressions (P<0.01, P<0.05), and in increasing Bcl-2 protein expression (P<0.05). CONCLUSION: EA combined with Zhuang-medicine-thread moxibustion can reduce blood glucose and improve gastrointestinal motility in DGP rats, which may be related to its effect in regulating of Caspase-3, Bax and Bcl-2 expression.

[Effect of electroacupuncture combined with Zhuang-medicine-thread moxibustion on oxidative stress in gastric antrum of diabetic gastroparesis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Zhuang-medicine-thread moxibustion on oxidative stress-related indicators in diabetic gastroparesis (DGP) rats, so as to explore its mechanism underlying improvement of DGP. METHODS: Male SD rats were randomly divided into normal, model, medication, EA, Zhuang-medicine-thread moxibustion (moxibustion) and EA+Zhuang-medicine-thread moxibustion (combination) groups (15 rats in each group). The DGP model was established by intraperitoneal injection of streptozotocin (STZ). Rats of the medication group were treated by gavage of 0.15 mg/mL mosapride citrate suspension（10 mL/kg）. EA (10 Hz/50 Hz, 2 mA, 20 min) or Zhuang-medicine-thread moxibustion (3 cones) was applied to "Zhongwan" (CV12), bilateral "Neiguan" (PC6) and bilateral "Sanyinjiao" (SP6) of the related groups, once a day for 3 weeks. The body weight, blood glucose, gastric emptying rate and intestinal propulsion rate of rats were measured. The serum malondialdehyde (MDA) content was measured by thiobarbituric acid method, the serum supero-xide dismutase (SOD) activity was measured by xanthine oxidase method, and the serum reactive oxygen species (ROS) activity was detected by ELISA. HE staining was used to observe the pathological changes of gastric antrum. The expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), nicotin-amide adenine dinucleotide phosphate oxidases (NOX4), peroxisome proliferators activated receptor-gamma coactivator 1α(PGC-1α) proteins and mRNAs in gastric antrum was detected by Western blot and real-time quantitative PCR, respectively. RESULTS: Compared with the normal group, the body weight, gastric emptying rate, intestinal propulsion rate, serum SOD activity, the expressions of HO-1, PGC-1α, total Nrf2 proteins and mRNAs, and Nrf2 nuclear translocation in gastric antrum were decreased (P<0.01), while the blood glucose, serum MDA content and ROS activity, NOX4 protein and mRNA expressions in gastric antrum were increased (P<0.01) in the model group. Compared with the model group, the blood glucose was decreased in the EA, moxibustion and combination groups (P<0.01); the body weight, gastric emptying rate, intestinal propulsion rate, and the expressions of HO-1 and PGC-1α mRNAs in gastric antrum were all increased in the four treatment groups (P<0.01, P<0.05), while the serum MDA content and ROS activity, NOX4 protein and mRNA expressions in gastric antrum were all decreased (P<0.01); the serum SOD activity and total Nrf2 protein expression in gastric antrum were increased in medication, moxibustion and combination groups (P<0.01, P<0.05); the expressions of HO-1 and PGC-1α proteins, and Nrf2 nuclear translocation in gastric antrum were increased in medication and combination groups (P<0.05, P<0.01); the expression of Nrf2 mRNA was increased in the medication, EA and combination groups (P<0.01, P<0.05). Compared with the combination group, the body weight, gastric emptying rate and intestine propulsion rate were decreased in the medication, EA and moxibustion groups(P<0.01, P<0.05), and the blood glucose increased (P<0.01); the serum MDA content and ROS activity, NOX4 protein and mRNA expressions in gastric antrum were increased (P<0.01, P<0.05), serum SOD activity, and the expressions of total Nrf2 protein, PGC-1α protein and mRNA, HO-1 mRNA in gastric antrum were decreased (P<0.01, P<0.05) in the EA and moxibustion groups; the expression of Nrf2 mRNA was decreased in the moxibustion group (P<0.05). HE staining showed a large number of inflammatory cell infiltration in the lamina propria and submucosa, and the gastric glands in the lamina propria were significantly expanded, the submucosa was severely edematous in the model group, which were relative milder in the four treatment groups. CONCLUSION: EA combined with Zhuang-medicine-thread moxibustion can effectively improve the activity of antioxidant enzymes, reduce the production of lipid peroxide, and regulate the expression of antioxidant related proteins and genes, which may be one of the mechanisms in treating DGP.

[Effect of electroacupuncture combined with Zhuang-medicine-thread moxibustion on silent information regulator-1/nuclear factor κB signaling pathway in gastric antrum of diabetic gastroparesis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with Zhuang-medicine-thread moxibustion on silent information regulator-1 (SIRT1)/nuclear factor kappa B (NF-κB) signal pathway and inflammatory factor expression in gastric antrum tissue of diabetic gastroparesis (DGP) rats, so as to explore its mechanism underlying improvement of DGP. METHODS: Male SD rats were randomly divided into normal, model, medication, EA, Zhuang-medicine-thread moxibustion (moxibustion) and EA+moxibustion groups (n=12 per group). The DGP model was established by intraperitoneal injection of streptozotocin (STZ). Rats of the medication group were treated by gavage of 0.15 mg/mL mosapride citrate suspension. EA (10 Hz /50 Hz, 2 mA) or moxibustion (3 cones) or EA+moxibustion was applied to "Zhongwan"(CV12), bilateral "Neiguan"(PC6) and bilateral "Sanyinjiao"(SP6) of the related group for 20 min, once a day for 3 weeks. Blood glucose, gastric emptying rate and intestinal propulsion rate were measured. The levels of serum interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-α(TNF-α) were detected by ELISA; the phosphorylation level of the phosphorylated inhibitor of nuclear factor κBα inhibitor (pIκ-Bα), the protein and mRNA expression of NF-κB p65 and SIRT1 in the gastric antrum tissue were detected by Western blot and real-time quantifitative PCR, respectively. RESULTS: (1) Compared with the normal group, the levels of blood glucose, serum IL-6, IL-8, TNF-α, and gastric pIκ-Bα and NF-κB p65 protein and mRNA expressions were significantly increased (P<0.01), and the gastric emptying rate, intestinal propulsion rate, serum IL-10 level, and SIRT1 protein and mRNA expressions were considerably decreased in the model group (P<0.01). (2) In contrast to the model group, the blood glucose in the EA, moxibustion and EA+moxibustion groups, serum IL-6, IL-8 and TNF-α levels in the 4 treatment groups, as well as NF-κB p65 protein expression in the medication and EA+moxibustion groups, and NF-κB p65 mRNA expression and pIκ-Bα protein and mRNA expression in the 4 treatment groups were significantly decreased (P<0.01, P<0.05); while the gastric emptying rate and intestinal propulsive rate and IL-10 content in the 4 treatment groups, and SIRT1 protein and mRNA expression in the medication and EA+moxibustion groups were obviously increased (P<0.05, P<0.01). (3) The effects of EA+moxibustion were significantly superior to those of simple EA and moxibustion in increasing gastric emptying rate, IL-10, SIRT1 protein expression (P<0.05, P<0.01), and in lowering IL-8 and TNF-α contents, pIκ-Bα protein and mRNA expression and NF-κB p65 mRNA expression (P<0.05, P<0.01). No significant differences were found among the 4 intervention groups in promoting the intestinal propulsive rate and among the EA, moxibustion and EA+moxibustion groups in lowering blood glucose (P>0.05). CONCLUSION: EA combined with Zhuang-medicine-thread moxibustion can effectively reduce the level of serum inflammatory factors and regulate SIRT1/NF-κB signal pathway in DGP rats, which may contribute to its function in improving gastrointestinal movement.

[Effect of electroacupuncture on 5-HT7R in gastric antrum and colon tissues of functional diarrhea rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) at "Zusanli"(ST36), "Yinlingquan" (SP9) or "Yingu"(KI10) on the expression of 5-hydroxytryptamine type 7 receptor (5-HT7R) in the gastric antrum and colon tissues in functional diarrhea (FD) model rats, so as to explore its mechanisms underlying improving FD. METHODS: Forty male SD rats were randomly divided into control, model, ST36, SP9 and KI10 groups，with 8 rats in each group. The FD model was established by combined administration of restriction (four-limbs' banding) + abdominal cold stimulation + feeding every other day, for 14 days. EA (2 Hz, 0.5 mA) was applied to bilateral ST36 or bilateral SP9 or bilateral KI10 in the 3 corresponding groups for 30 min, once a day for 7 days after successful modeling. Rats of the control group received restriction only. The fecal water content was calculated and the stool form score was given according to the Bristol's methods. The gastric residual rate (GRR) and small intestine propulsion rate (SIPR) were determined to assess the motility of the gastrointestinal tract. Immunohistochemical and real-time fluorescent quantitative PCR were used to detect the expression of 5-HT7R protein and mRNA of the gastric antrum and colon tissues, respectively. RESULTS: Compared with the control group, the fecal water content, the stool form score, the SIPR and the expression levels of 5-HT7R protein and 5-HT7R mRNA were significantly increased (P<0.01,P<0.05) and the GRR was considerably decreased in the model group (P<0.01). The fecal water content, stool form score and SIPR, and expression level of 5-HT7R protein and mRNA in the gastric antrum and colon were significantly lower in both the ST36 and SP9 groups (not in the KI10 group) than in the model group (P<0.01, P<0.05), but the GRR was significantly higher in the ST36 and SP9 groups (not in the KI10 group) than in the model group (P<0.01). The effects of both ST36 and SP9 were significantly superior to those of KI10 in improving all the indexes mentioned above （except SIPR and the mRNA level of 5-HT7R in the colon in SP9 group）(P<0.01, P<0.05). No significant differences were found between the ST36 and SP9 groups in lowering the levels of fecal water content, stool form score, SIPR, and the expression of 5-HT7R protein and mRNA, as well as in up-regulating GRR (P>0.05). CONCLUSION: EA of ST36 and SP9 can improve the motility of gastrointestinal tract in FD rats, which may be related to its functions in down-regulating the expression of 5-HT7R protein and mRNA in gastric antrum and colon tissues. The effects of ST36 and SP9 were obviously better than those of KI10 in ameliorating the gastric and intestinal motility (except GRR) and in lowering the expression of 5-HT7R protein and mRNA.

[A Case of Neoadjuvant Chemotherapy with Modified FOLFOXIRI plus Bevacizumab for Transverse Colon Cancer with Invasion of the Gastric Antrum].

A 66-year-old male diagnosed with transverse colon cancer was admitted to our hospital. Computed tomography, colonoscopy, and esophagogastroduodenoscopy revealed locally advanced cancer with invasion of the gastric antrum. We staged the disease as cT4a, cN2, cM0, Stage ⅢB, with wild-type RAS expression. We performed an ileostomy prior to administering chemotherapy. The patient received 4 courses of modified FOLFOXIRI plus bevacizumab and 2 courses of FOLFIRI. The size of the tumor noticeably decreased after chemotherapy. The patient experienced grade 3 neutropenia, anorexia, and oral mucositis during chemotherapy. We performed a right hemicolectomy(D3), partial gastrectomy and ileum resection after administering neoadjuvant chemotherapy. The pathological stage of the disease was ypT2, ypN0, ypM0, ypStageⅠ, and the effect of the chemotherapy was Grade 1b. After the resection, he received mFOLFOX6 and CapeOX for 3 months as adjuvant chemotherapy. He remained cancer-free for 1 year and 3 months after the surgery. This result suggests that preoperative modified FOLFOXIRI plus bevacizumab chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.

Proton Pump Inhibitors Prevent Gastric Antral Ulcers Induced by NSAIDs via Activation of Capsaicin-Sensitive Afferent Nerves in Mice.

BACKGROUND/AIMS: We examined the effects of proton pump inhibitors (PPIs) on gastric antral ulcers induced by non-steroidal anti-inflammatory drugs in re-fed mice and the role of capsaicin-sensitive afferent nerves (CSANs) in the protective effects of PPIs on the antral mucosa. METHODS: Male mice were administered indomethacin after 2 h of re-feeding of diet after a 24-h fast, and gastric lesions were examined 24 h after indomethacin dosing. The effects of PPIs (lansoprazole and omeprazole), histamine H2-receptor antagonists (H2-RAs, famotidine, ranitidine), capsaicin and misoprostol on the formation of antral ulcers induced by indomethacin were examined. Functional ablation of CSANs was caused by pretreatment of mice with a high dose of capsaicin. RESULTS: Indomethacin produced lesions selectively in the gastric antrum in re-fed conditions. Formation of antral ulcers was not affected by H2-RAs, but inhibited by PPIs, capsaicin and misoprostol. The anti-ulcer effect of lansoprazole was 30 times stronger than that of omeprazole. Antral ulcers induced by indomethacin were markedly aggravated in mice with ablated CSANs. The effects of PPIs and capsaicin on ulcer formation were inhibited by ablation of CSANs, pretreatment with a capsaicin receptor antagonist (capsazepine/ruthenium red) and an inhibitor of nitric oxide synthesis (L-NAME). However, the inhibitory effect of misoprostol was not prevented by the ablation of CSANs or drugs. CONCLUSIONS: The results suggested that CSANs play an important role in protection of the antral mucosa and that both lansoprazole and omeprazole are capable of preventing NSAID-induced antral ulcers by activating CSANs.

Central neuropeptide-S administration alleviates stress-induced impairment of gastric motor functions through orexin-A.

BACKGROUND/AIMS: The novel brain peptide neuropeptide-S (NPS) is produced exclusively by a small group of cells adjacent to the noradrenergic locus coeruleus. The NPSR mRNA has been detected in several brain areas involved in stress response and autonomic outflow, such as amygdala and hypothalamus, suggesting that central NPS may play a regulatory role in stress-induced changes in gastrointestinal (GI) motor functions. In rodents, exogenous central NPS was shown to inhibit stress-stimulated fecal output. Moreover, exogenous NPS was demonstrated to activate hypothalamic neurons that produce orexin-A (OXA), which has been shown to stimulate postprandial gastric motor functions via central vagal pathways. Therefore, we tested whether OXA mediates the NPS-induced alterations in gastric motor functions under stressed conditions. MATERIALS AND METHODS: We investigated the effect of central exogenous NPS on solid gastric emptying (GE) and gastric postprandial motility in acute restraint stress (ARS)-loaded conscious rats. The OXA receptor antagonist SB-334867 was administered centrally prior to the central NPS injection. The expression of NPSR in the hypothalamus and dorsal vagal complex was analyzed by immunofluorescence. RESULTS: Central administration of NPS restored the ARS-induced delayed GE and uncoordinated postprandial antro-pyloric contractions. The alleviative effect of NPS on GE was abolished by pretreatment of the OX1R antagonist SB-334867. In addition to hypothalamus, NPSR was detected in the dorsal motor nucleus of vagus, which suggest a direct stimulatory action of exogenous NPS on gastric motility. CONCLUSION: NPS may be a novel candidate for the treatment of stress-related gastric disorders.

Efficacy of Juzen-taiho-to against vincristine-induced toxicity in dogs.

Vincristine, one of the anti-cancer drugs used in veterinary practice, has adverse hematological and gastrointestinal effects in dogs. Juzen-taiho-to is a traditional Chinese medicine used for patients with anorexia in human medicine. However, the protective effects of Juzen-taiho-to against anti-cancer drug-induced toxicity in dogs have not been investigated. We therefore examined whether the administration of Juzen-taiho-to to dogs affects gastric motility, and vincristine-induced gastrointestinal and hematological toxicity. The study was composed of three trials. In the first trial, Juzen-taiho-to (450 mg/kg/day) was orally administered to five dogs. In the second and third trials, vincristine (0.75 mg/m2) was intravenously administered to each dog in the absence or presence of Juzen-taiho-to (450 mg/kg/day). During these trials, gastric motility and blood parameters were assessed. Juzen-taiho-to increased gastric motility and improved vincristine-induced gastrointestinal, but not hematological, adverse effects in dogs. This study suggested that Juzen-taiho-to may be applicable for gastrointestinal care in dogs receiving chemotherapy.

Genotypic determination of resistance and heteroresistance to clarithromycin in Helicobacter pylori isolates from antrum and corpus of Colombian symptomatic patients.

BACKGROUND: The effectiveness of Helicobacter pylori first-line treatment has decreased drastically with the rise of strains resistant to clarithromycin. Therapy failure has also been described in patients with infections by strains with dissimilar antimicrobial susceptibilities. The present study aims to estimate the prevalence of resistance and heteroresistance to clarithromycin in H. pylori isolates from antrum and corpus of Colombian patients. METHODS: The study material included 126 isolates from antrum and corpus biopsies from 63 symptomatic patients over 18 years old who had a gastric endoscopy performed on them between June 2014 to August 2016. PCR amplification and sequencing of the H. pylori 23S rDNA gene was performed to determine the presence of mutations associated with clarithromycin resistance. Random amplified polymorphic DNA analysis was implemented in cases of resistance and heteroresistance. RESULTS: The overall frequency of resistance to clarithromycin was 38.1% (24/63 patients), of which 19 patients had resistant isolates in both stomach segments (14 with A2143G mutation and 5 with A2142G mutation), and 5 patients had a heteroresistant status. The remaining 61.9% (39/63 patients) presented only susceptible isolates. DNA fingerprinting analysis showed different patterns in 4/22 paired isolates. CONCLUSIONS: The high prevalence of H. pylori clarithromycin-resistance obtained (> 15%) constitutes an alert for gastroenterologists and suggests the need for reconsideration of the current eradication regimen for H. pylori in the studied population. The data show that heteroresistance status is an additional factor to be considered in the assessment of resistance. In consequence, it is advisable to examine at least two biopsies from different gastric segments.

Bmi1 marks gastric stem cells located in the isthmus in mice.

In the mammalian stomach, the isthmus has been considered as a stem cell zone. However, various locations and proliferative activities of gastric stem cells have been reported. We focused here on the stem cell marker Bmi1, a polycomb group protein, aiming to elucidate the characteristics of Bmi1-expressing cells in the stomach and to examine their stem cell potential. We investigated the Bmi1-expressing cell lineage in Bmi1-CreERT; Rosa26-YFP, LacZ or Rosa26-Confetti mice. We examined the in vivo and ex vivo effects of Bmi1-expressing cell ablation by using Bmi1-CreERT; Rosa26-iDTR mice. The Bmi1 lineage was also traced during regeneration after high-dose tamoxifen-, irradiation- and acetic acid-induced mucosal injuries. In the lineage-tracing experiments using low-dose tamoxifen, Bmi1-expressing cells in the isthmus of the gastric antrum and corpus provided progeny bidirectionally, towards both the luminal and basal sides over 6 months. In gastric organoids, Bmi1-expressing cells also provided progeny. Ablation of Bmi1-expressing cells resulted in impaired gastric epithelium in both mouse stomach and organoids. After high-dose tamoxifen-induced gastric mucosal injury, Bmi1-expressing cell lineages expanded and fully occupied all gastric glands of the antrum and the corpus within 7 days after tamoxifen injection. After irradiation- and acetic acid-induced gastric mucosal injuries, Bmi1-expressing cells also contributed to regeneration. In conclusion, Bmi1 is a gastric stem cell marker expressed in the isthmus of the antrum and corpus. Bmi1-expressing cells have stem cell potentials, both under physiological conditions and during regeneration after gastric mucosal injuries. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM: To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori (H. pylori)-infected patients in Ireland. METHODS: DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype HelicoDR assay. cagA and vacA genotypes were investigated using PCR. RESULTS: Primary, secondary and overall resistance rates for clarithromycin were 50.5% (n = 53/105), 78.3% (n = 47/60) and 60.6% (n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2% (n = 16/105) and 28.3% (n = 17/60) and 20% (n = 33/165), respectively. Resistance to both antibiotics was 12.4% (n = 13/105) in treatment-naïve patients, 25% (n = 15/60) in those previously treated and 17% (n = 28/165) overall. A cagA-positive genotype was detected in 22.4% (n = 37/165) of patient samples. The dominant vacA genotype was S1/M2 at 44.8% (n = 74/165), followed by S2/M2 at 26.7% (n = 44/165), S1/M1 at 23.6% (n = 39/165) and S2/M1 at 4.8% (n = 8/165). Primary clarithromycin resistance was significantly lower in cagA-positive strains than in cagA-negative strains [32% (n = 8/25) vs 56.3% (n = 45/80) P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vacA s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vacA s2 genotype, [41% (n = 32/78) vs 77.8% (n = 21/27) P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status. CONCLUSION: Genotypic H. pylori clarithromycin resistance is high and cagA-negative strains are dominant in our population. Less virulent (cagA-negative and vacA S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.

[Effect of Different Stimulating Strength of Electroacupuncture on Gastrointestinal Motility and RhoA/ROCK Signaling in Gastric Antral Smooth Muscle in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effect of different strength of electroacupuncture (EA) stimulation on gastrointestinal motility and Ras homolog gene family member (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) signaling in diabetic gastroparesis (DGP) rats, so as to reveal the underlying mechanisms of EA for improving DGP. METHODS: Sixty SD rats were randomly and equally divided into blank control, DGP model, weak EA, medium EA, and strong EA groups (n＝12 rats in each). The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 55 mmol/kg, 2%) and high-sugar and high-fat fodder feeding for 8 weeks. EA (0.12, 0.24, 0.36 mA, 20 Hz/100 Hz) was applied to "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) for 20 min, once daily for 15 successive days. Blood glucose levels were measured weekly with blood glucose meter and blood glucose test paper. Fecal phenol red excretion method was used to display gastric emptying and small intestinal propulsion function. The expression of RhoA protein in the gastric antral smooth muscle tissue was detected by immunohistochemistry and Western blot (WB), separately, and that of ROCK, myosin phosphatase target subunit 1 (MYPT 1) and phosphorylated (p)-MYPT 1 proteins in gastric antrum detected by WB. RESULTS: Compared with the blank control group, the gastric emptying rate and small intestine propulsion rate of the model group were significantly decreased (P<0.05), and the blood glucose level was remarkably increased (P<0.05). Moreover, the expression levels of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins in the gastric antrum were significantly down-regulated relevant to the control group (P<0.05). After administration of EA, the decreased gastric emptying rate and intestinal propulsion rate, and the down-regulated expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins were significantly increased in the strong, medium and weak EA stimulation groups (P<0.05). Comparison among the 3 EA groups showed that the strong stimulation was significantly superior to weak stimulation in up-regulating the expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins, and obviously superior to the medium stimulation in up-regulating RhoA and MYPT 1 protein levels (P<0.05), while the medium stimulation was significantly stronger than the weak stimulation in up-regulating the expression of ROCK, MYPT 1 and p-MYPT 1 proteins (P<0.05). There were no significant differences among the 3 EA groups in up-regulating the gastric emptying rate and small intestinal propulsion rate, and between the strong stimulation and medium stimulation in the expression levels of ROCK and p-MYPT 1 proteins (P>0.05). CONCLUSION: Electroacupuncture stimulation of ST 36-SP 6-ST 21 at 0.12, 0.24 and 0.36 mA can promote the gastrointestinal motility in DGP rats, which may be associated with its effects in enhancing RhoA/ROCK signaling in the gastric antral smooth muscle at different degrees.

Accidental Concentrated Hydrogen Peroxide Ingestion Associated with Portal Venous Gas.

A case of a 52-year old male patient who presented to the emergency department with severe nausea and vomiting following accidental ingestion of H2O2. A computed tomography (CT) abdomen performed at our institution demonstrated extensive portal venous gas throughout the liver with few gas droplets seen in the extrahepatic portal vein portion. Pneumatosis was also noted in the wall of the gastric antrum. Upper GI Endoscopy was done revealing diffuse hemorrhagic gastritis and mild duodenal bulb erosion. The patient was treated with hyperbaric oxygen. On the second day of admission, the patient was able to eat without difficulty or pain. Accidental ingestion of high concentration H2O2 solution has been shown to cause extensive injury to surrounding tissues. The injury occurs via three main mechanisms: corrosive damage, oxygen gas formation, and lipid peroxidation. We report a case of accidental ingestion of a highly concentrated (35%) solution of H2O2 causing portal venous gas.

[Effect of Electroacupuncture Intervention on Gastrointestinal Motility and Expression of Insulin-like Growth Factor 1 and Its Receptor Proteins in Gastric Antrum in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention of "Zusanli"(ST 36), etc. on gastrointestinal motility and levels of insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1 R) proteins in the gastric antrum in diabetic gastroparesis (DGP) rats, so as to study its mechanism underlying improvement of DGP. METHODS: Fifty SD rats, half male and half female, were randomly allocated to control, model, EA acupoint, EA non-acupoint and medication (metoclopramide) groups (n=10 rats/group). The DGP model was induced by 2% streptozotocin (STZ, i.p.i.,55 mg/kg) and high fat-sugar forage for 8 weeks. EA (10 Hz/50 Hz, 2 mA) was applied to "Zusanli"(ST 36), "Liangmen"(ST 21), "Sanyinjiao"(SP 6) and non-acupoints (about 5 mm lateral to ST 36, ST 21 and SP 6, respectively) for 20 min, one daily for 15 days, and 1.7% metocloppramide (1 mL/100 g) was given (gavage) to rats of the medication group, once daily for 15 days. After the treatment, the rats' general conditions were scored, the blood glucose level was determined using a glucometer, and the gastrointestinal mobility was evaluated by measuring the gastric emptying rate (GER) and the intestinal propulsion rates (IPR) marked by oral-infused phenol red solution (50 mg/dL). The immunoactivity levels of IGF-1 and IGF-1 R of gastric antrum tissue were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: After modeling, the symptom integrative score, the blood glucose, IGF-1 and IGF-1 R levels were significantly increased (P<0.01), and the GER and IPR were notably decreased relevant to the control group (P<0.01). After EA stimulation of ST 36, ST 21 and SP 6, the symptom score, blood glucose, and IGF-1 and IGF-1 R levels of the gastric antrum were significantly reduced, while the GER and IPR were considerably increased (P<0.05,P<0.01). Except the GER and IPR were considerably increased in the medication group(P<0.05,P<0.01), no significant changes were found in the symptom integrative score, the blood glucose, IGF-1 and IGF-1 R levels in both EA non-acupoint and medication groups relevant to the model group (P>0.05),the GER and IPR in the EA non-acupoint group (P>0.05). Compared with the EA acupoint group, the symptom integrative score, IGF-1 and IGF-1 R levels were significantly increased in both EA non-acupoint and medication groups(P<0.05,P<0.01). CONCLUSIONS: EA stimulation can improve gastrointestinal motility and lower blood glucose in DGP rats, which may be closely associated with its effectiveness in reducing IGF-1 and IGF-1 R immunoactivity levels in gastric antrum.