Serum exosomal microRNAs as potential biomarkers for centrally mediated abdominal pain syndrome.

Centrally mediated abdominal pain syndrome (CAPS) has generated a heavy disease burden worldwide. This study aimed to explore the serum exosomal microRNAs as potential diagnostic biomarkers for CAPS. From September 2022 to October 2023, 97 patients with CAPS and 96 healthy subjects were enrolled. Differentially expressed serum exosomal miRNAs between patients with CAPS and healthy controls were identified by high-throughput sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The Receiver Operating Characteristic (ROC) curves and multivariate logistic regression analysis were used to evaluate the diagnostic value of the serum exosomal miRNAs. MiR-6850-5p, miR-194-5p, miR-199a-3p, miR-4525 which were significantly downregulated in serum exomes of CAPS patients compared to healthy controls which yielded the AUC values of 0.914 (95% CI, 0.873-0.954), 0.767 (95% CI, 0.695-0.839), 0.617 (95% CI, 0.527-0.708) and 0.561 (95% CI, 0.465-0.656), respectively to distinguish CAPS patients from healthy subjects. And AUC of the integration of the above 4 miRNAs was 0.931 (95% CI, 0.896-0.966). Multivariate logistic regression indicated that hsa-miR-6850-5p (OR=0.046; p<0.001), anxiety (OR=7.670; p=0.025) and depression (OR=22.967; p=0.008) were the independent predictors of CAPS. Serum exosomal miR-6850-5p is a promising diagnostic biomarker for CAPS. PERSPECTIVE: This study may be the first to explore serum exosomal miRNAs as a new diagnostic biomarker for CAPS, and the findings may help clinicians to access comprehensive understanding and accurate diagnosis of CAPS.

The Clinical Characteristics and Related Factors of Centrally Mediated Abdominal Pain Syndrome.

INTRODUCTION: The aim of this study was to explore the clinical characteristics and related factors of centrally mediated abdominal pain syndrome (CAPS). METHODS: Our study included 73 patients with CAPS and 132 age-matched and gender-matched healthy controls. The general information of the participants was collected, and the questionnaires were completed including the 7-item Generalized Anxiety Disorder Scale, 9-item Patient Health Questionnaire, Hamilton Anxiety Scale, Hamilton Depression Scale Pittsburgh Sleep Quality Index, Visual Analog Scale, and Short-Form 36. Univariate and forward stepwise regression analyses were performed to explore the influencing factors of CAPS. RESULTS: Nonexercise (adjusted odds ration [AOR] 4.53; confidence interval [CI] 1.602-12.809), mild-to-moderate depression (AOR 7.931; CI 3.236-19.438), married status (AOR 3.656; CI 1.317-10.418), and drinking coffee (AOR 0.199; CI 0.051-0.775) were found to be related with centrally mediated abdominal syndrome. The Hamilton Anxiety Scale score (7-13) was significantly related to moderate-to-severe abdominal pain (AOR 7.043; CI 1.319-37.593). Higher Hamilton Depression Scale score was related to lower mental component scale score (ß = -0.726, P < 0.01) and physical component scale score (ß = -0.706, P < 0.01). DISCUSSION: Depression, married status, and nonexercise were the independent risk factors of CAPS. Conversely, coffee intake was an independent protective factor of CAPS. Anxiety was related to the severity of abdominal pain, while depression was related to low health-related quality of life.

Acupuncture Improved the Function of the Lower Esophageal Sphincter and Esophageal Motility in Chinese Patients with Refractory Gastroesophageal Reflux Disease Symptoms: A Randomized Trial.

Objectives: Acupuncture is therapeutic for refractory gastroesophageal reflux disease by an unclear mechanism. This study was aimed at investigating the effect of acupuncture on esophageal motility in patients with symptoms of refractory gastroesophageal reflux disease. Methods: Sixty-eight patients with refractory gastroesophageal reflux disease symptoms were prospectively enrolled from August 2014 to December 2018 and randomized into acupuncture and control groups (n = 33 and 35, respectively). The acupuncture group received acupuncture, and the control group received sham acupuncture. Pre- and post-acupuncture high-resolution manometry was performed to evaluate the effect of acupuncture on esophageal motility. The GerdQ questionnaire was used to evaluate the pre- and post-intervention symptoms. Results: After acupuncture, there was a significant increase in the length of lower esophageal sphincter (3.10 ± 1.08 cm vs. 3.78 ± 1.01 cm), length of intra-abdominal lower esophageal sphincter (2.14 ± 1.05 cm vs. 2.75 ± 1.16 cm), and mean basal pressure of lower esophageal sphincter (22.02 ± 10.03 mmHg vs. 25.06 ± 11.48 mmHg) in the acupuncture group (P = 0.014); moreover, the numbers of fragmented contraction and ineffective contraction decreased from 36 to 12 (P < 0.001) and 43 to 18 (P = 0.001), respectively, in the acupuncture group. However, no significant difference was observed in the control group. The GerdQ score decreased significantly from 9.45 ± 2.44 to 7.82 ± 2.21 points in the first week after acupuncture (P < 0.001). Conclusions: Acupuncture, which improves esophageal motility, has short-term efficacy in patients with symptoms of refractory gastroesophageal reflux disease. This trial is registered with Chinese Clinical Trial Registry (ChiCTR1800019646).

Risk factors of Clostridium difficile infection in patients with inflammatory bowel disease accompanied with diarrhea and its impact on short-term prognosis / 中华消化杂志

Objective To analyze the prevalence of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) accompanied with diarrhea in order to analyze the possible risk factors and its impact on short-term prognosis.Methods From January 2013 to June 2015,a total of 169 IBD patients with diarrhea who visited Rui Jin Hospital,School of Medicine,Shanghai Jiaotong University were enrolled,and in the same period 184 non-IBD patients with diarrhea were enrolled as control group.Clinical data of IBD patients with diarrhea were collected.Clostridium difficile toxins A and B of stool specimens of all included patients were detected with enzyme immunoassay.T test,chi-square test and logistic regression analysis were performed for statistical analysis.Results Among 169 IBD patients with diarrhea,there were 137 adults and 32 children.The positive rate of CDI of IBD patients with diarrhea (9.5％,16/169) was higher than that of non-IBD patients with diarrhea (1.1％,2/184),and the difference was statistically significant (x2 =12.785,P ＜ 0.0l).The positive rate of CDI in adults and children with IBD accompanied with diarrhea were 7.3％ (10/137),and 18.8％ (6/32),respectively.Among 16 CDI-positive IBD patients with diarrhea,10 patients had hospitalization history before admission,and the rate of previous hospitalizations was higher than that of CDI-negative IBD patients with diarrhea (37.3％,57/153),and the difference was statistically significant (x2 =2.875,P =0.01,odds ratio (OR) =1.26,95％ confidence interval (CI) 0.78 to 2.03).Furthermore,among 16 CDI-positive IBD patients with diarrhea,14 patients had been treated with antibiotic drugs before,the antibiotic utilization rate was higher than that of CDI-negative IBD patients with diarrhea (34.6％,53/153),and the difference was statistically significant (x2 =14.778,P ＜ 0.01,OR =24.74,95％ CI 3.15 to 194.46).However,there was no statistically significant difference in the length of hospitalization,incidence of bowel surgery and usage of inflaximab within six months after Clostridium difficile detection between the CDI-positive group and CDInegative group of 1BD patients with diarrhea (all P ＞ 0.05).Conclusions The incidence of CD1 in IBD patients with diarrhea increases.The risk factors include history of previous hospitalization before admission and antibiotic usage.However there is no significant correlation between CDI and short-term prognosis of IBD.

Effects of TNF-related apoptosis-inducing ligand on cell apoptosis of pancreatic cancer / 中华胰腺病杂志

Objective To investigate the mechanism of TNF-related apoptosis-inducing ligand (TRAIL) promoting apoptosis of pancreatic cancer cells SW1990, Patu8988 and BxPC3. Methods Three kinds of pancreatic cancer cells SW1990, Patu8988 and BxPC3 were transfected with the pCA13 plasmid carrying TRAIL gene ( pCA13 TRAIL group) and the blank plasmid control ( pCA13 group) , respectively. The expression of TRAIL mRNA in transfected cells was detected by RT-PCR, and the expression of TRAIL protein was detected by Western blot. The apoptosis rate and expression of TRAIL receptor R1 and R2 were detected by flow cytometry. Apoptosis was detected by TUNEL and Hoechst double staining, and observed by electron microscopy. The expression of caspase-3 in transfected cells was detected by immunohistochemistry. Results SW1990, Patu8988 and BxPC3 cells can expresse TRAIL mRNA and protein within 24 h after transfection. The apoptotic rate at 24 h after transfection was (27. 30 ± 5. 14)％, (13. 52 ± 0. 95)％ and (31. 40 ± 8. 70)％,respectively, which was higher than that of pCA13 group [(10. 58 ± 1. 88)％,(8. 42 ± 0. 46)％ and (16.11 ±1.66)％], respectively. The expression rates of TRAIL-R1 were (61.37 ± 3.05)％,(42.10 ± 5. 11)％ and (36. 64 ± 4. 84)％, respectively, and the expression rates of TRAIL-R2 were (36. 20 ± 4. 83)％,(37. 26 ± 8. 46)％ and (24. 32 ± 3. 71)％, respectively,which were higher than those of pCA13 group except PATU8988 cells. Positivity rates of caspase-3 were ( 14. 64 ± 5. 35 )％, ( 9. 92 ± 5. 50 )％ and (16. 12 ± 6. 74)％, which were obviously higher than ( 3. 01 ± 1. 50 )％, ( 1. 75 ± 0. 50 )％ and ( 3. 79 ± 1. 58)％ in pCA13 group,and the differences were statistically significant(P<0. 05). Conclusions TRAIL could up-regulate the expression of TRAIL R1 and R2 in multiple pancreatic cancer cell lines in vitro, and thus promote cell apoptosis.

Role of colonic mast cell infiltration and nerve growth factor in visceral hypersensitivity of irritable bowel syndrome / 中华消化杂志

Objective To investigate the role of mucosal mast cells infiltration and degranulation with nerve growth factor (NGF)in development of visceral hypersensitivity in Sprague-Dawley (SD)rats. Methods The model of visceral hypersensitivity of irritable bowel syndrome (IBS)was established in 19 neonate SD rats with intestinal stimulation (rectalballon distention)on 8th,10th and 12th postnatal days. The other 19 neonate SD rats without colonic distention were assigned to the control group.After rats grew up (six to eight weeks old),the visceral sensitivity was tested by abdominal withdrawal reflex (AWR)in 10 rats of each group.Mast cell infiltration and degranulation were observed with toluidine blue staining in colon tissue slides.The NGF level of intestinal tissues was detected by enzyme-linked immunosorbent assay (ELISA)methods in the left nine rats of each group.The culture system of dorsal root ganglias (DRG)from the neonatal rats was set up.The changes of electrophysilogical characters of DRG stimulated with NGF (100 ng/mL)for four days were recorded with patch-clamp.Paired t test was performed for comparison between groups.Results The results of AWR indicated that neonatal colonic stimulation could significantly increase visceral sensitivity after growing up.Under 20,40 and 60 mmHg (1 mmHg=0.133 kPa)distention pressure,visceral sensitivity scores of visceral hypersensitivity rats and rats of control group were 1 .00±0.50 vs 1 .67 ±0.50,1 .89 ±0.31 vs 2.89 ±0.34 and 2.89 ±0.33 vs 3.89±0.33,the differences were statistically significant (t=-2.83,-6.00 and -6.00,all P <0.05 ). The results of master cells staining in tissue slides showed colonic master cells infiltration was obvious in rats with visceral hypersensitivity,and part of mast cells were degranulation.The result of ELISA demonstrated that NGF level of visceral hypersensitivity rats was significantly higher than that of control group ((11.07±3.06)pg/mg vs (2.38 ±1.88)pg/mg,t =-6.93,P <0.05).The results of electrophysilogical tests of primary cultured DRG indicated that compared with blank control growp,the action potential threshold of neuron in NGF 100 ng/mL group significantly decreased ((-18.0±2.1 )mV vs (-29.0 ± 2.5 )mV,t = 12.26,P <0.05)and discharge frequency increased ((5 .0± 1 .4 )/800 ms vs (12.0 ± 3.2)/800 ms,t=-8.40,P <0.05 ).Meanwhile,neuron voltage-gated K+ current density remarkably decreased,most were sustained delayed rectifier K+ current (I K )decreasing ((279.0 ±48.0)pA/pF vs (203.0±39.0)pA/pF,t=6.18,P <0.05).Conclusion Colonic stimulation in neonatal rats could cause intestinal master cells infiltration and degranulation,which induced changes of neuron electrophysilogical characters and resulted in visceral hypersensitivity after growing up.

Effects of acupuncture on esophageal motility of patients with refractory gastroesophageal reflux disease / 中华消化杂志

Objective To investigate the effects of acupuncture on the improvement of esophageal motility disorder in patients with refractory gastroesophageal reflux disease (GERD).Methods From September 2012 to March 2014,40 patients with refractory GERD were enrolled and evenly divided into the treatment group and the control group. High resolution esophageal impedance manometry was conducted in patients.After the first examination,patients of the control group lay down for 30 minutes, and patients of the treatment group received acupuncture treatment at Neiguan,Gongsun and Zusanli points for 30 minutes.Then all the patients underwent high resolution esophageal impedance manometry again.ManoView ESO 3.0 software was used for analysis.The parameters included swallowing peristalsis defect,lower esophageal sphincter (LES)pressure,LES residual pressure,LES length,upper esophageal sphincter (UES)pressure,distal wave amplitude,peristalsis duration time,starting speed of peristalsis wave,speed of edge contraction and integration of the peristaltic waves.Chi-square test or t test was performed for data analysis.Results The percentage of normal swallows of the treatment group before and after treatment was 56.0% (112/200)and 74.0% (148/200),the percentage of delayed esophageal emptying was 31 .5 % (63/200 )and 11 .5 % (23/200 ),and the differences were statistically significant (χ2 =14.242 and 23.700,both P 0.05 ).The LES resting pressure of the treatment group before and after treatment was (20.2 ±18.8)mmHg (1 mmHg=0.133 kPa)and (26.3±10.1)mmHg,the length of LES was (2.2 ±0.6 )cm and (3.3 ±0.8)cm,the distal esophageal peristaltic amplitude was (60.2 ± 21 .9)mmHg and (41 .1 ± 16.8 )mmHg,and the differences were statistically significant (t = 5 .519, 6.580 and 6.881 ,all P 0.05 ).There as no significant difference in LES resting pressure and LES residual pressure of the control group before and after lying down (both P >0.05 ).However,before and after lying down,there were significant differences in the length of LES ((2.3 ±0.6)cm vs (2.5 ±0.6)cm) and UES resting pressure ((67.4 ±21 .2 )mmHg vs (53.5 ±18.1 )mmHg)in the control group (t =2.530 and 6.652,both P 0.05).Before and after lying down,there was no significant difference in distal wave amplitude,duration of peristalsis,the beginning speed of the peristaltic wave and CFV of the control group (all P >0.05 ).Conclusion Acupuncture can help increase the LES resting pressure,extend the length of LES,improve the overall peristaltic pressure and completeness of esophageal somatic part,meanwhile,it increases the percentage of normal swallows of patients with refractory GERD.

The relation between gastroesophageal reflux disease with or without esophageal injury and esophageal motility and acid reflux / 中华消化杂志

Objective To study the relation of esophageal motility and acid reflux between gastroesophageal reflux disease (GERD) patients with and without esophageal injury.Methods A total of 25 patients who met the GERD diagnosis criteria were conducted esophageal-gastric-duodenal endoscopy examination and followed with high-resolution esophageal manometry.The changes of esophageal pH postprandial were also detected.The differences of esophageal motility and acid reflux time between GERD patients with and without esophageal injury were compared.Patients were divided into non-acid reflux group and acid reflux group according to DeMeester score.The changes of esophageal motility indexes of these two groups were compared.Wilcoxon test and t test were used for statistical analysis.Results There was no significant difference in baseline value of lower esophageal sphincter (LES) pressure,remained LES pressure,speed of the esophageal peristalsis,the time of esophageal pH＜4 and DeMeester score between groups with and without esophageal injury (all P＞0.05).But esophageal contraction amplitude of group with esophageal injury was lower than that of group without esophageal injury (31.9 mm Hg vs 64.2 mm Hg,1 mm Hg=0.133 kPa,Z=-2.37,P=0.02).There was no significant difference in baseline value of LES pressure,remained LES pressure,speed of the esophageal peristalsis between acid reflux group and non acid reflux group (all P＞0.05).But the esophageal contraction amplitude of acid reflux group was lower than that of non acid reflux group (36.4 mm Hg vs 71.8 mm Hg,Z=-2.25,P=0.02).Conclusions There was no significant correlation between the LES pressure and esophageal acid reflux with esophageal injury in GERD patients.Esophageal peristalic contraction may be associated with esophageal injury and acid reflux.

Analysis of the effect of omeprazole and tegaserod on non-erosive reflux disease / 中国实用内科杂志

0.05).Conclusion Omeprazole and Tegaserod improved the reflux symptoms of the NERD patients.Omeprazole improves abnormal acid exposure but not abnormal bile exposure.Tegaserod improved neither abnormal acid exposure nor abnormal bile exposure.