ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software， and the protein-protein interaction （PPI） network for key targets was depicted. Finally， the hub gene was determined through topological analysis. Auto Dock， PyMOL， and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments， a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin（HE） staining， uric acid test， enzyme linked immunosorbent assay（ELISA）， Western blot， and real-time polymerase chain reaction（Real-time PCR）， the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values， 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response， astrocyte activation， regulation of interleukin （IL）-8 production， nuclear receptor activity， and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway， advanced glycosylation end/receptor of advanced glycation endproducts（AGE/RAGE） signaling pathway， anti-inflammatory， and other pathways. PPI network indicated that albumin（ALB）， peroxisome proliferator-activated receptor-γ （PPAR-γ）， IL-6， IL-1β， and C-reactive protein（CRP） were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene （β-carotene）. Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose （7.76 g·kg^-1·d^-1）， medium-dose （15.53 g·kg^-1·d^-1）， and high-dose （31.05 g·kg^-1·d^-1） groups of Buyang Huanwu Tongfeng decoction had different degrees of remission， and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration， as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced， followed by the medium-dose and low-dose groups， and the expression of ALB， PPAR-γ， IL-6， IL-1β， and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB， PPAR-γ， IL-6， IL-1β， and CRP， inhibiting the PPAR-γ/nuclear transcription factor （NF）-κB pathway， and reducing AGEs/RAGE-mediated inflammation， Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Objective:Diabetic retinopathy (DR) is the most common cause of adult blindness in China. Screening of DR is important for early detection, prevention, and treatment. However, there is still controversy in the research on the prevalence and risk factors of DR in China. This study was designed to evaluate the prevalence of DR and related risk factors in patients with type 2 diabetes mellitus in Beijing City.Methods:A cross-sectional survey was conducted in in Dongcheng District and Tongzhou District, Beijing City. Patients with type 2 diabetes aged 18-80 years were selected from four communities, and all subjects underwent questionnaires, physical examinations, laboratory examinations and fundus photography. The logistic regression model was used to analyze the associated factors of DR.Results:A total of 1 531 subjects were included, with the median age of 66 years old and the average age of (65.6±7.4) years old, and the glycosylated hemoglobin level in the subjects was 7.2%±1.3%, and the glycosylated hemoglobin compliance rate was 56.0%(857/1 531). A total of 254 patients with diabetic retinopathy were detected, and the prevalence of DR was 16.6%(254/1 531). Among them, there were 218 cases of non-proliferative diabetic retinopathy and 36 cases of proliferative diabetic retinopathy. Compared with the non-DR group, there were statistically significant differences in fasting blood glucose ( Z=-3.74, P<0.001), glycosylated hemoglobin( Z=-10.664, P<0.001), urinary microalbumin excretion rate( Z=-7.767, P<0.001), low-density lipoprotein cholesterol( Z=-2.589, P=0.01), and duration of diabetes( Z=-10.189, P<0.001) between the DR group and the non-DR group. Multivariate regression analysis showed that the duration of diabetes ( OR=1.08, 95% CI: 1.06-1.10, P<0.001), glycosylated hemoglobin ( OR=1.38, 95% CI: 1.23-1.55, P<0.001), and FPG ( OR=1.11, 95% CI: 1.03-1.19, P=0.008) were associated factors for DR. Conclusion:In this study, the prevalence of DR in 4 communities of type 2 diabetes in Beijing City was 16.6%. Besides, this study further confirmed that the duration of diabetes, fasting blood glucose levels, and glycosylated hemoglobin are associated factors for DR in patients with type 2 diabetes.

Objective:Diabetic retinopathy (DR) is the most common cause of adult blindness in China. Screening of DR is important for early detection, prevention, and treatment. However, there is still controversy in the research on the prevalence and risk factors of DR in China. This study was designed to evaluate the prevalence of DR and related risk factors in patients with type 2 diabetes mellitus in Beijing City.Methods:A cross-sectional survey was conducted in in Dongcheng District and Tongzhou District, Beijing City. Patients with type 2 diabetes aged 18-80 years were selected from four communities, and all subjects underwent questionnaires, physical examinations, laboratory examinations and fundus photography. The logistic regression model was used to analyze the associated factors of DR.Results:A total of 1 531 subjects were included, with the median age of 66 years old and the average age of (65.6±7.4) years old, and the glycosylated hemoglobin level in the subjects was 7.2%±1.3%, and the glycosylated hemoglobin compliance rate was 56.0%(857/1 531). A total of 254 patients with diabetic retinopathy were detected, and the prevalence of DR was 16.6%(254/1 531). Among them, there were 218 cases of non-proliferative diabetic retinopathy and 36 cases of proliferative diabetic retinopathy. Compared with the non-DR group, there were statistically significant differences in fasting blood glucose ( Z=-3.74, P<0.001), glycosylated hemoglobin( Z=-10.664, P<0.001), urinary microalbumin excretion rate( Z=-7.767, P<0.001), low-density lipoprotein cholesterol( Z=-2.589, P=0.01), and duration of diabetes( Z=-10.189, P<0.001) between the DR group and the non-DR group. Multivariate regression analysis showed that the duration of diabetes ( OR=1.08, 95% CI: 1.06-1.10, P<0.001), glycosylated hemoglobin ( OR=1.38, 95% CI: 1.23-1.55, P<0.001), and FPG ( OR=1.11, 95% CI: 1.03-1.19, P=0.008) were associated factors for DR. Conclusion:In this study, the prevalence of DR in 4 communities of type 2 diabetes in Beijing City was 16.6%. Besides, this study further confirmed that the duration of diabetes, fasting blood glucose levels, and glycosylated hemoglobin are associated factors for DR in patients with type 2 diabetes.

Objective:To investigate whether dual-energy computed tomography(DECT) measurement of monosodium urate(MSU) crystal loading can predict the risk of gout flares.Methods:A single-center, prospective, observational study included 229 gout patients initially diagnosed at the Gout Clinic of Qingdao University from August 2021 to February 2022. The patients underwent MSU assessment of the bilateral feet using DECT. Following enrolment, all patients commenced uric acid-lowering therapy(ULT) and were followed up at 3 and 6 months. Patients who experienced at least one flare within 6 months were compared with those who did not, and the odds ratio( OR) for the risk of gout flares was calculated. Results:Patients who experienced gout flare had a significantly longer disease duration[(6.69±5.42) vs(4.14±4.86) years, P<0.01], a higher number of flares in the past year(4.80±1.73 vs 2.02±1. 23, P<0.01), a higher proportion of fatty livers(11.0% vs 1.4%, P<0.05), and a greater volume of MSU crystals in the feet[(3.52±9.74) vs(0.29±0.98)cm 3,P<0.05] compared to patients without gout flare. The results of the multifactorial logistic regression analysis indicated that the number of flares in the past year( OR=1.295, 95% CI 1.032-1.613, P<0.05) and feet MSU crystal volume( OR=3.245, 95% CI 1.164-9.064, P<0.05) were independent risk factors for gout flares. The receiver operating characteristic(ROC) curve indicated the integration of the MSU prediction model into the clinical prediction model resulted in a comprehensive prediction model with an area under curve(AUC) value of 0.780(95% CI 0.710-0.840), sensitivity of 0.83, and specificity of 0.62. Internal validation of the comprehensive prediction model using the Bootstrap method yielded a C-index of 0.770(95% CI 0.701-0.833) for predicting flares. The calibration curve of the model demonstrated a good fit between the predicted probability of flares and the actual probability, indicating high calibration accuracy. Conclusion:The volume of MSU crystals in the feet is an independent risk factor for flares following ULT. A larger volume of MSU crystals in the foot increases the likelihood of a flare. This study provides a basis for early prediction of flare and a reference for early preventive treatment.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Objective To establish a prediction model for tuberculosis incidence in Nantong area by multivariate regression analysis, and to provide theoretical support for the implementation of combined prevention work in this area. Methods A total of 37 338 registered patients with pulmonary tuberculosis in Nantong City from 2010 to 2021 were enrolled in the observation group. A total of 28,721 healthy people who underwent physical examination during the same period were selected as the control group. Results From 2010 to 2021, there were a total of 37 338 cases of pulmonary tuberculosis in central Nantong. From 2010 to 2015, more than 3,000 cases were reported annually, with the largest number (4 142 cases) in 2011, accounting for 11.09% of the total. The number of cases reported from 2016 to 2021 was all less than 3 000, and the number of cases reported from 2021 was the least , 1 803 cases, accounting for 4.83% of the total. The number of cases decreased each year in the past 12 years. The incidence of pulmonary tuberculosis in males was 70.97% (26 497 cases) and that in females was 29.03% (10 841 cases). In terms of age, the lowest incidence rate was 0.06% (23 cases) in the age group of 0-9 years old, and the highest incidence rate was 19.56% (7 304 cases) in the age group of 60-69 years old. Logistics regression analysis showed that male, age ≥60 years old, occupation as a farmer and smoking history were the risk factors for pulmonary tuberculosis (P < 0.05). ROC curve results showed that the AUC value of the risk prediction model for pulmonary tuberculosis in the Nantong area was 0.872, with a predictive sensitivity of 86.32% and a specificity of 89.21%. Conclusion There are many risk factors for pulmonary tuberculosis in Nantong area, and different factors interact and influence each other. The construction of a risk prediction model for pulmonary tuberculosis can better predict the clinical incidence, which is helpful to guide clinical diagnosis and treatment.

Objective:To explore the clinical application value of salivary pepsin test (Peptest) in the diagnosis of gastroesophageal reflux disease (GERD).Methods:From April to October 2022, at the Department of Gastroenterology of the First Affiliated Hospital of Nanjing Medical University, a total of 81 patients with typical reflux and (or) heartburn symptoms for more than 1 month, who were diagnosed with GERD and completed 24-hour esophageal pH impedance monitoring (24 h MII-pH) and high-resolution esophageal manometry were enrolled. Salivary samples were collected after lunch, at the onset of symptoms, and at random time point on the day of intubation, and all patients received standard dose of proton pump inhibitor (PPI) for 2 weeks. The 24 h MII-pH results were taken as the gold standard for diagnosing GERD. The optimal time point of Peptest and the diagnostic value of combination of Peptest and PPI test in GERD diagnosis were analyzed. The 24 h MII-pH negative patients were further divided into Peptest-positive group and Peptest-negative group. The heartbrun scores, gastroesophageal reflux disease questionnaire (GERD-Q), reflux characteristics, and esophageal motility between the 2 groups were compared and to investigate the differential diagnostic value of Peptest in 24 h MII-pH negative patients. Chi-square test and non-parametric test were used for statistical analysis.Results:The results of 24 h MII-pH indicated that 21 patients (25.9%, 21/81) were diagnosed GERD and 60 patients were negative for 24 h MII-pH. The onset of symptoms was the optimal time point for Peptest, with a sensitivity of 80.9%, a specificity of 50.0%, and an accuracy of 58.0%. The specificity and accuracy of Peptest at the onset of symptoms combined with PPI test in GERD diagnosis were higher than those of Peptest at the onset of symptoms alone (75.0% vs. 50.0%, 74.1% vs. 58.0%), and the differences were statistically significant ( χ2=8.00 and 4.65, P=0.005 and 0.031). Among 60 cases of 24 h MII-pH negative patients, 30 were positive for Peptest at the onset of symptoms and 30 were negative for Peptest at the onset of symptoms. The heartburn scores and GERD-Q scores of Peptest-positive group were both higher than those of Peptest-negative group (3.0 (2.0, 3.0) vs. 1.0 (0.0, 2.3), 12.0 (9.8, 13.0) vs. 9.0 (6.0, 11.0) ); the clearance time of acid reflux of Peptest-positive group was longer than that of Peptest-negative group (57.0 s (22.3 s, 88.0 s) vs. 18.3 s (9.6 s, 32.1 s) ); the lower esophageal sphincter resting pressure and integrated relaxation pressure were lower than those of Peptest-negative group (10.40 mmHg (5.75 mmHg, 18.95 mmHg) vs. 21.45 mmHg (10.65 mmHg, 31.70 mmHg), 3.90 mmHg (2.05 mmHg, 5.35 mmHg) vs. 4.90 mmHg (3.76 mmHg, 8.25 mmHg); 1 mmHg=0.133 kPa); the distal mean nocturnal baseline impedance, the distal contractile integral and esophagogastric junction contractile integral were all lower than those of Peptest-negative group ( 1 783 Ω (1 660 Ω, 2 157 Ω) vs. 2 300 Ω(1 805 Ω, 2 370 Ω), 1 416 mmHg·s·cm (919 mmHg·s·cm, 2 176 mmHg·s·cm) vs. 1 858 mmHg·s·cm (1 395 mmHg·s·cm, 2 880 mmHg·s·cm), 27.7 mmHg·cm (19.8 mmHg·cm, 39.5 mmHg·cm) vs. 52.6 mmHg·cm (27.7 mmHg·cm, 74.6 mmHg·cm) ), and the differences were statistically significant ( Z=-4.00, -3.53, -3.31, -2.34, -2.13, -2.75, -2.14 and -2.43; P<0.001, <0.001, =0.001, =0.019, =0.033, =0.006, =0.032 and =0.015). Conclusions:Peptest may be better at diagnosing GERD at the onset of symptoms compared to postprandial, random time points, and the accuracy of diagnosing GERD further improves when combined with PPI test. Peptest at the onset of symptoms may have differential diagnostic value for GERD patients in 24 h MII-pH negative patients.

Objective:To explore the efficacy and influencing factors of linaclotide in patients with functional defecation disorder (FDD).Methods:From June 1, 2021 to February 28, 2023, at the First Affiliated Hospital of Nanjing Medical University, 160 patients with FDD were enrolled and randomly divided into linaclotide group and polyethylene glycol group by using a random number table method, with 80 cases in each group, and the treatment course both was 4 weeks. The efficacy, weekly complete spontaneous bowel movement (CSBM), patient assessment of constipation symptom (PAC-SYM), numerical rating scale (NRS), Zung′s self-rating anxiety scale (SAS) and Zung′s self-rating depression scale (SDS) before and after treatment of linaclotide group and polyethyetylene glycol group were recorded and compared. Multivariate logistic regression analysis was performed to analyze the factors affected linaclotide in the treatment of FDD (including anorectal manometry). Receiver operating characteristic curve (ROC) was used to analyze the predictive value of risk factors on the efficacy of linaclotide in FDD. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:After treatment, the weekly CSBM frequencies of linaclotide group and polyethylene glycol group were both higher than those before treatment in the same group (3.20±2.03 vs. 2.44±2.09, 3.10±2.26 vs. 2.58±2.06), and the differences were statistically significant ( t=-4.85 and -5.91, both P<0.001). After treatment, PAC-SYM score of stool shape, rectal symptom, abdominal symptom and total score, NRS score, SAS score and SDS score of linaclotide group and polyethylene glycol group were all lower than those before treatment in the same group (1.41±0.96 vs. 1.89±1.13, 0.95±0.49 vs. 1.14±0.46, 0.69±0.57 vs. 1.00±0.58, 0.96±0.43 vs. 1.23±0.40, 1.54±1.11 vs. 2.48±1.24, 43.54±6.26 vs. 45.13±7.30, 42.10±7.95 vs. 43.78±9.15 and 1.36±1.09 vs. 1.88±1.17, 0.83±0.40 vs. 1.10±0.45, 0.81±0.60 vs. 1.01±0.69, 0.91±0.42 vs. 1.21±0.41, 1.90±1.17 vs. 2.23±1.27, 43.55±7.72 vs. 44.61±8.51, 40.00±6.71 vs. 41.18±7.50), and the differences were statistically significant ( t=7.08, 7.73, 7.15, 9.26, 7.66, 7.96, 8.46, 7.26, 7.16, 5.78, 8.37, 6.17, 4.67 and 7.13, all P< 0.001). After treatment, the NRS score of linaclotide group was lower than that of polyethylene glycol group, and the difference was statistically significant ( t=-2.01, P=0.046). The total effective rate of linaclotide group was higher than that of polyethylene glycol group (77.5%, 62/80 vs. 62.5%, 50/80), and the difference was statistically significant ( χ2=4.29, P=0.038). The results of multivariate logistic regression analysis showed that the threshold of initial sensory volume and maximum tolerable volume were independent risk factors for linaclotide treatment of FDD ( OR=0.965, 95% confidence interval 0.936 to 0.995, P=0.022; OR=0.980, 95% confidence interval 0.962 to 0.999, P=0.041). The results of ROC analysis showed that the efficacy of linaclotide was poor in FDD patients with the threshold of initial sensory volume >67.5 mL or maximum tolerable volume > 117.5 mL. The combined predictive value of initial sensory volume and maximum tolerable volume threshold was higher than that of individual prediction, with an area under the curve of 0.722, sensitivity of 79.0% and specificity of 55.6%. Conclusions:Linaclotide can improve CSBM, constipation symptoms, abdominal pain and psychological status of FDD patients. The initial sensory volume threshold and maximum tolerable volume threshold are independent risk factors of the efficacy of linaclotide in FDD treatment and have certain predictive value in efficacy.