1.Mechanisms of Gegen Qinlian Tang-containing Serum in Improving 5-FU Sensitivity by Inhibiting Glycolysis in Colorectal Cancer Cells Based on CDK16/MYC Pathway
Rong CAI ; Shang WANG ; Fuqing CHENG ; Yanping ZHOU ; Zuowei HU ; Yunhai LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):1-9
ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang (GQT) inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cells based on the cyclin-dependent kinase 16 (CDK16)/MYC proto-oncogene (MYC) pathway. MethodsHCT-116/5-FU cells were treated with different concentrations (5%, 10%, 20%, 30%) of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU, GQT, and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine (EDU) staining and annexin V-FITC/PI double staining, respectively. Glucose consumption, adenosine triphosphate (ATP) production, and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins, CDK16, MYC, and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation (CoIP) was used to examine the protein interaction between CDK16 and MYC, and cycloheximide (CHX) treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells, significant inhibition was observed only at 5 mg·L-1 5-FU (P<0.05), which was used for model establishment. Compared with 5-FU alone, addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability (P<0.05), with stronger inhibition at higher serum concentrations. Thus, 5% GQT-containing serum was used in subsequent experiments. Compared with the control group, 5-FU, GQT, and 5-FU + GQT treatments all significantly reduced cell proliferation (P<0.05) and increased apoptosis (P<0.01). The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone (P<0.01), accompanied by more pronounced reductions in glucose consumption, ATP production, and lactate generation (P<0.01). Additionally, compared with control, 5-FU, and GQT groups, the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms (P<0.01) and greater inhibition of glycolytic enzymes, including hexokinase 2 (HK2), 3-phosphoinositide-dependent protein kinase 1 (PDK1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) (P<0.01). CDK16, MYC, and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group (all P<0.01). MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group (P<0.05), which was rescued by CDK16 overexpression (P<0.05). ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU, potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.
2.Mechanisms of Gegen Qinlian Tang-containing Serum in Improving 5-FU Sensitivity by Inhibiting Glycolysis in Colorectal Cancer Cells Based on CDK16/MYC Pathway
Rong CAI ; Shang WANG ; Fuqing CHENG ; Yanping ZHOU ; Zuowei HU ; Yunhai LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):1-9
ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang (GQT) inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cells based on the cyclin-dependent kinase 16 (CDK16)/MYC proto-oncogene (MYC) pathway. MethodsHCT-116/5-FU cells were treated with different concentrations (5%, 10%, 20%, 30%) of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU, GQT, and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine (EDU) staining and annexin V-FITC/PI double staining, respectively. Glucose consumption, adenosine triphosphate (ATP) production, and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins, CDK16, MYC, and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation (CoIP) was used to examine the protein interaction between CDK16 and MYC, and cycloheximide (CHX) treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells, significant inhibition was observed only at 5 mg·L-1 5-FU (P<0.05), which was used for model establishment. Compared with 5-FU alone, addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability (P<0.05), with stronger inhibition at higher serum concentrations. Thus, 5% GQT-containing serum was used in subsequent experiments. Compared with the control group, 5-FU, GQT, and 5-FU + GQT treatments all significantly reduced cell proliferation (P<0.05) and increased apoptosis (P<0.01). The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone (P<0.01), accompanied by more pronounced reductions in glucose consumption, ATP production, and lactate generation (P<0.01). Additionally, compared with control, 5-FU, and GQT groups, the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms (P<0.01) and greater inhibition of glycolytic enzymes, including hexokinase 2 (HK2), 3-phosphoinositide-dependent protein kinase 1 (PDK1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) (P<0.01). CDK16, MYC, and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group (all P<0.01). MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group (P<0.05), which was rescued by CDK16 overexpression (P<0.05). ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU, potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.
3.A Study on the Risk of Cardiovascular Health and Pelvic Inflammatory Disease Based on the 2013-2018 National Health and Nutrition Examination Survey Data
Shuangshuang XIE ; Yangxue YIN ; Liming YUAN ; Lingyun LIAO ; Qin XU ; Yanping ZHANG ; Rong ZHOU
Journal of Practical Obstetrics and Gynecology 2025;41(5):400-405
Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95%CI 0.97-0.99,P<0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P<0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P>0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.
4.Development, reliability, and validity of a treatment-related quality of life scale for Chinese patients with multiple myeloma
Chunyan SUN ; Zhen CAI ; Bing CHEN ; Lijuan CHEN ; Wenming CHEN ; Kaiyang DING ; Juan DU ; Rong FU ; Chengcheng FU ; Da GAO ; Guangxun GAO ; Yanjuan HE ; Jian HOU ; Ming JIANG ; Fei LI ; Jian LI ; Juan LI ; Zhenyu LI ; Aijun LIAO ; Jing LIU ; Jun LUO ; Jianmin LUO ; Yanping MA ; Jianqing MI ; Ting NIU ; Hongling PENG ; Yongping SONG ; Luqun WANG ; Rong ZHAN ; Xi ZHANG ; Yu HU
Chinese Journal of Hematology 2025;46(8):713-721
Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.
5.miR-21-5p Targetes STAT3 Reduce the OGD/R-induced Neuronal Injury
Yanping LI ; Qingyun LI ; Rong HUO ; Xiaolin DONG ; Hongmei LI ; Huan WEI ; Yi ZENG
Journal of Kunming Medical University 2025;46(5):12-20
Objective To investigate the potential mechanism of miR-21-5p in alleviating cerebral ischemia-reperfusion injury by targeting STAT3.Methods The HT22 cells were induced by OGD/R to construct a cell model of cerebral ischemia reperfusion injury.The expression of miR-21-5p was detected by RT-qPCR.The CCK-8 assay,TUNEL staining and flow cytometry were respectively used to detect the cell viability and apoptosis.ELISA assay was used to determine the contents of inflammatory factors IL-6,IL-10 and TNF-α in the cell supernatant.Western blot was used to detect the expression levels of p-STAT3/STAT3,Cleaved-Caspase-3,Bax and Bcl-2 proteins.The TargetScan database was used to predict the binding sites of miR-21-5p and STAT3.The dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-21-5p and STAT3.Results The relative expression level of miR-21-5p was down-regulated in HT22 cells which induced by OGD/R(P<0.001).The cell viability(P<0.0001)was decreased and the apoptosis rate(P<0.001)was increased in OGD/R induced-HT22 cells.The contents of pro-inflammatory factors IL-6(P<0.001)and TNF-α(P<0.001)was increased,while the content of anti-inflammatory factor IL-10(P<0.001)decreased.After transfection with miR-21-5p mimic,cell viability was enhanced,apoptosis rate was reduced and neuroinflammation was inhibited.MiR-21-5p could target and bind to STAT3.After miR-21-5p inhibitor transfection,cell viability decreased,apoptosis was promoted,and neuroinflammation occurred;STAT3 inhibitor Stattic could reverse the effect of miR-21-5p inhibitor.Conclusion MiR-21-5p could specifically bind to STAT3 and reduce the neuroinflammation and apoptosis of OGD/R induced-HT22 cells.
6.Study on Correlation Between Traditional Chinese Medicine Syndrome Elements and Risk Factors in Patients with Type Ⅱ Cardio-renal Syndrome
Rong YU ; Hanchao HUANG ; Huan DENG ; Wenli DING ; Yanping ZENG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(7):1568-1573
Objective To investigate the correlation between traditional Chinese medicine(TCM)syndrome elements and risk factors in patients with type Ⅱ cardio-renal syndrome(CRS).Methods A retrospective analysis was conducted on the medical records of 116 patients with type Ⅱ CRS.The distribution of TCM syndrome elements was analyzed,and the correlation between the syndrome elements and risk factors of gender,age,smoking history,alcohol consumption history,coronary heart disease,hypertension,diabetes,and anemia were evaluated.Results(1)The analysis of syndrome elements of 116 patients with type Ⅱ CRS showed that the main disease-location elements were heart(96 cases,82.76%),lung(89 cases,76.72%),kidney(81 cases,69.83%),spleen(71 cases,61.21%),and liver(25 cases,21.56%);the main disease-nature elements were qi deficiency(113 cases,97.41%),blood deficiency(96 cases,82.76%),yang deficiency(95 cases,81.89%),phlegm(94 cases,81.03%),yin deficiency(90 cases,77.59%),dampness(61 cases,52.59%),water retention(55 cases,47.41%),and blood stasis(47 cases,40.52%).(2)The analysis of age groups of 116 patients with type Ⅱ CRS showed that the majority of the patients were middle-aged and elderly individuals over 60 years old,and the age groups covered<60 years old(4 cases,3.45%),61-70 years old(10 cases,8.62%),71-80 years old(28 cases,24.14%),81-90 years old(64 cases,55.17%),and>90 years old(10 cases,8.62%).(3)The analysis of gender of 116 patients with type Ⅱ CRS showed that 46 cases(39.66%)were male,and 70 cases(60.34%)were female,the female outnumbering the male.(4)The exploration of correlation between TCM syndrome elements and risk factors with Logistic regression analysis showed that blood deficiency was positively correlated with alcohol consumption,hypertension,and anemia(P<0.05 or P<0.01),yang deficiency was positively correlated with anemia(P<0.05),yin deficiency was positively correlated with smoking and diabetes(P<0.05),dampness was positively correlated with smoking and anemia(P<0.01),water retention was positively correlated with gender and protein abnormalities(P<0.05 or P<0.01),and blood stasis was positively correlated with hypertension(P<0.05).Conclusion The illness of type Ⅱ CRS is located in the heart,involving the five organs,and is closely related to the lungs and kidneys.The general pathogenesis of type Ⅱ CRS is characterized by being deficiency of qi and yang in the root cause,and having the symptom manifestations of phlegm and blood stasis.In type Ⅱ CRS patients,men are more likely to suffer water retention,smokers are more likely to suffer yin deficiency and dampness,drinkers are more likely to suffer blood deficiency,individuals with hypertension are more likely to suffer blood deficiency and blood stasis,individuals with diabetes are more likely to suffer yin deficiency,individuals with anemia are more likely to suffer blood deficiency,yang deficiency and dampness,and individuals with protein abnormalities are more likely to suffer water retention.
7.A Study on the Risk of Cardiovascular Health and Pelvic Inflammatory Disease Based on the 2013-2018 National Health and Nutrition Examination Survey Data
Shuangshuang XIE ; Yangxue YIN ; Liming YUAN ; Lingyun LIAO ; Qin XU ; Yanping ZHANG ; Rong ZHOU
Journal of Practical Obstetrics and Gynecology 2025;41(5):400-405
Objective:To analyze the relationship between Cardiovascular Health(CVH)and Pelvic Inflamma-tory Disease(PID)using data from the National Health and Nutrition Examination Surveys(NHANES).Meth-ods:Participants from the NHANES database were extracted based on the inclusion of PID,LE8 scores,and mul-tiple potential confounding factors,excluding those with missing variables.Multivariate Logistic regression analysis was conducted using R to assess the relationship between the CVH and the risk of PID.Additionally,subgroup a-nalysis and interaction tests were performed for age,race,poverty,marital status,education,BMI,menstrual regu-larity,and pregnancy history.Results:A total of 3934 female participants were included,with an average age of 39.95±11.42 years.Multivariable Logistic regression analysis showed that after adjusting for age,race,BMI,edu-cation level,marital status,household income,menstrual cycle,and pregnancy history,the risk of PID gradually decreased with an increase in CVH assessment metric LE8 scores(OR 0.98,95%CI 0.97-0.99,P<0.001).Stratified analysis indicated significant interactions between age,race,and marital status in the association be-tween CVH and PID(interaction P<0.05 for all),while household income level,education level,BMI,menstrual regularity,and pregnancy history showed no significant interactions with the CVH and PID association(P>0.05).Conclusions:There is a significant negative relationship between CVH and PID in adult women in the United states,suggesting that better cardiovascular health may help reduce the risk of PID.
8.Development, reliability, and validity of a treatment-related quality of life scale for Chinese patients with multiple myeloma
Chunyan SUN ; Zhen CAI ; Bing CHEN ; Lijuan CHEN ; Wenming CHEN ; Kaiyang DING ; Juan DU ; Rong FU ; Chengcheng FU ; Da GAO ; Guangxun GAO ; Yanjuan HE ; Jian HOU ; Ming JIANG ; Fei LI ; Jian LI ; Juan LI ; Zhenyu LI ; Aijun LIAO ; Jing LIU ; Jun LUO ; Jianmin LUO ; Yanping MA ; Jianqing MI ; Ting NIU ; Hongling PENG ; Yongping SONG ; Luqun WANG ; Rong ZHAN ; Xi ZHANG ; Yu HU
Chinese Journal of Hematology 2025;46(8):713-721
Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.
9.Clinical symptoms and epidemiological characteristics of 57 patients with tsutsugamushi disease in Yunxi County, Shiyan City, Hubei Province in 2022
Xiao XIONG ; Shiping HAN ; Meihe CAI ; Qin ZHAO ; Yanping ZHONG ; Jing MAO ; Junjie YANG ; Xinhua LIU ; Kangxiao LIU ; Rong RAO ; Feifei LEI ; Fangmin SONG ; Huabing TAN
Chinese Journal of Endemiology 2024;43(5):388-392
Objective:To analyze the clinical symptoms and epidemiological characteristics of patients with tsutsugamushi disease (TD) in Utica County, Shiyan City, providing reference for scientific prevention and control of TD.Methods:The information of 57 TD patients admitted to the Department of Infectious Diseases of the People's Hospital of Utica County in Shiyan City from January to December 2022 was collected, including age, gender, occupation, clinical manifestations (tarsus or chigger, high fever, rash and accompanying syndromes), laboratory and imaging test results, and field work and travel history. Blood samples and body crusts were collected, and enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect antibodies against Orientia tsugamushi (Ot-Ab-IgM) and Orientia tsutsugamushi (Ot). The scores of each patient were calculated using the TD Diagnostic Scale. A score of ≥8.5 was considered a clinical diagnosis of TD. According to the number of system functional damages (0, 1, 2, ≥3), 57 patients were divided into 4 groups, A, B, C, and D, TD was analyzed for system functional damages of each system.Results:Among the 57 TD patients, 26 (45.61%) were male and 31 (54.39%) were female, and the proportion of patients aged 40 - 79 years was 92.98% (53/57); farmers accounted for 89.47% (51/57). May was the peak of TD incidence, with 19 cases, which accounted for 33.33% (19/57) of the total number of patients affected that year. Fifty-four patients had a history of fieldwork or field trips before the onset of the disease. The incidence of high fever in 57 TD patients was 100.00%(57/57), the detection rate of body scorch or chiggers was 80.70% (46/57), and the incidence rate of rash was 98.25% (56/57); the incidence rate of tsutsugamushi disease triad (accompanied by scabs, high fever, and rash) was 80.70% (46/57); the incidence of eosinophil decline was 100.00%(57/57), and 77.19% (44/57) of TD patients experienced multiple-system functional damage (MSFD). The TD score diagnostic scale for 57 patients ranged from 8.5 to 10.5 points. After being hospitalized for 1 - 5 days, all TD patients experienced a decrease in body temperature to the normal range, and the damage to various systems functional gradually recovered.Conclusions:TD has become one of the most common natural infectious diseases in Utopia County, Shiyan City, Hubei Province. The patients are mainly middle-aged and elderly people, and the triple syndrome is a typical clinical manifestation. Asymptomatic injuries to the blood system, liver and kidneys are the most common.
10.Mechanism of dorsal root ganglion SERT in electroacupuncture regulation of P2X3 receptor-mediated visceral hypersensitivity in IBS rats
Rong HUANG ; Jing CHAI ; Yun ZHOU ; Yu QIAO ; Zhijun WENG ; Huangan WU ; Huirong LIU ; Lu ZHU ; Jindan MA ; Yi ZHU ; Fang ZHANG ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(6):435-446
Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

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