Objective:To observe and analyze the adverse drug reactions (ADRs) caused by adalimumab in patients with inflammatory bowel disease (IBD) and its influencing factors.Methods:A retrospective study was conducted on 106 patients with inflammatory bowel disease treated with adalimumab at Tianjin Medical University General Hospital from November 2019 to November 2023. Among them, 31 patients who experienced adverse reactions were included in the ADR group (case group), while 75 patients who did not experience adverse reactions were included in the non-ADR group (control group). Patients' basic information, laboratory tests, adverse drug reactions, etc were collected. Measurement data with normal distribution were expressed as xˉ± s and means between two groups were compared using independent samples t-test. The percentage of count data was calculated, and the rate between groups was compared by χ2 test. The risk factors of adverse drug reactions caused by adalimumab in patients with inflammatory bowel disease were analyzed by single factor screening and multivariable Logistic regression model. Results:ADR occurred in 31 of 106 patients, accounting for 29.25% (31/106), among those patients which infection was the most common,accounting for 18.87%(20/106). The number of combined drugs (≥3 kinds), drug allergy history, drug duration (≥3 months), blood concentration (>12 μg/mL) in ADR group were higher than those in non-ADR group ( χ2-values were 5.90, 5.78, 6.94 and 10.07, respectively,t-values were 8.55 and 0.97 respectively; all P<0.05). Multivariate Logistic regression results showed that the number of combined drugs ≥3, drug allergy history, drug duration >3 months, blood concentration >12 ng/L, creatinine and total bilirubin levels were all risk factors for adverse drug reactions of adalimumab in IBD patients (O R values were 2.680, 2.394, 3.228, 4.415, 3.673 and 4.646, respectively;95% CI:1.563~3.798, 1.434-3.354, 2.070-4.387, 3.803-5.027, 2.364-4.982 and 3.449-5.843, respectively; all P<0.05). Conclusion:The number of combined drugs ≥3, drug allergy history, drug duration >3 months, blood concentration >12 ng/L, creatinine and total bilirubin levels are all risk factors for adverse drug reactions in IBD patients with adalimumab. In clinical practice, it is necessary to strengthen monitoring and take timely preventive measures for IBD patients with the above-mentioned factors, in order to reduce the incidence of ADR.

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

Objective:To analyze the occurrence and influencing factors of adverse reactions in patients with inflammatory bowel disease (IBD) during the long-term treatment with vedolizumab (VDZ).Methods:The study was a retrospective observational design. The study subjects were selected from patients who long-termly used VDZ to treat moderate-to-severe active IBD in Tianjin Medical University General Hospital from February 1, 2021 to December 31, 2023. Clinical data of patients were collected through the hospital system of clinical pharmacy management, including general information, IBD condition, VDZ maintenance treatment plan, combination of drugs, laboratory test results, etc. The adverse reactions of VDZ were screened and their clinical manifestations, severity, intervention and outcomes were analyzed descriptively. The patients were divided into 2 groups according to whether VDZ adverse reactions occurred, and the differences in clinical data between them were compared; the influencing factors of adverse reactions were analyzed by multivariate logistic regression method.Results:A total of 142 patients were included in the study, including 81 males and 61 females, aged (37.6±6.4) years with a range from 18 to 57 years. There were 103 patients (72.5%) developed VDZ adverse reactions, which mainly involved skin (52 patients, account for 50.5%), digestive system (33 patients, account for 32.0%) and respiratory system (18 patients, account for 17.5%). All 103 patients did not stop VDZ treatment, and the adverse reaction symptoms disappeared or were relieved after symptomatic treatments. Compared with patients without VDZ adverse reactions, the age of patients with VDZ adverse reactions were higher [(39.5±5.4) years vs. (32.4±6.7) years], and the proportions of patients with chronic relapsing clinical type [65.0%(67/103) vs. 41.0%(16/39)], severe disease activity [60.2%(62/103) vs. 33.3%(13/39)], combined drug use [67.0%(69/103) vs. 46.2%(18/39)], and injecting VDZ once every 4 weeks during maintenance treatment [27.2%(28/103) vs. 10.3%(4/39)] in the group were larger, with statistical significance (all P<0.05). Multivariate logistic regression analysis showed that the chronic relapsing clinical type [odds ratio ( OR)=1.012, 95% confidence interval ( CI): 1.001-1.028, P=0.002], severe disease activity ( OR=1.096, 95% CI: 1.010-1.158, P=0.040), combination drugs ( OR=1.035, 95% CI: 1.003-1.122, P=0.041), VDZ maintenance therapy injection interval of 4 weeks ( OR=1.014, 95% CI: 1.002-1.113, P=0.005) were the risk factors for VDZ adverse reactions. Conclusions:Among IBD patients receiving long-term treatment of VDZ, the incidence of adverse reactions of VDZ was 72.5%, mainly involving skin, digestive system and respiratory system. Symptomatic treatments could be given, and the prognosis was good. Patients with chronic relapsing clinical type, severe disease activity, combination therapy, and shorter VDZ maintenance injection interval were at higher risk of adverse reactions.

Objective:To analyze the occurrence and influencing factors of adverse reactions in patients with inflammatory bowel disease (IBD) during the long-term treatment with vedolizumab (VDZ).Methods:The study was a retrospective observational design. The study subjects were selected from patients who long-termly used VDZ to treat moderate-to-severe active IBD in Tianjin Medical University General Hospital from February 1, 2021 to December 31, 2023. Clinical data of patients were collected through the hospital system of clinical pharmacy management, including general information, IBD condition, VDZ maintenance treatment plan, combination of drugs, laboratory test results, etc. The adverse reactions of VDZ were screened and their clinical manifestations, severity, intervention and outcomes were analyzed descriptively. The patients were divided into 2 groups according to whether VDZ adverse reactions occurred, and the differences in clinical data between them were compared; the influencing factors of adverse reactions were analyzed by multivariate logistic regression method.Results:A total of 142 patients were included in the study, including 81 males and 61 females, aged (37.6±6.4) years with a range from 18 to 57 years. There were 103 patients (72.5%) developed VDZ adverse reactions, which mainly involved skin (52 patients, account for 50.5%), digestive system (33 patients, account for 32.0%) and respiratory system (18 patients, account for 17.5%). All 103 patients did not stop VDZ treatment, and the adverse reaction symptoms disappeared or were relieved after symptomatic treatments. Compared with patients without VDZ adverse reactions, the age of patients with VDZ adverse reactions were higher [(39.5±5.4) years vs. (32.4±6.7) years], and the proportions of patients with chronic relapsing clinical type [65.0%(67/103) vs. 41.0%(16/39)], severe disease activity [60.2%(62/103) vs. 33.3%(13/39)], combined drug use [67.0%(69/103) vs. 46.2%(18/39)], and injecting VDZ once every 4 weeks during maintenance treatment [27.2%(28/103) vs. 10.3%(4/39)] in the group were larger, with statistical significance (all P<0.05). Multivariate logistic regression analysis showed that the chronic relapsing clinical type [odds ratio ( OR)=1.012, 95% confidence interval ( CI): 1.001-1.028, P=0.002], severe disease activity ( OR=1.096, 95% CI: 1.010-1.158, P=0.040), combination drugs ( OR=1.035, 95% CI: 1.003-1.122, P=0.041), VDZ maintenance therapy injection interval of 4 weeks ( OR=1.014, 95% CI: 1.002-1.113, P=0.005) were the risk factors for VDZ adverse reactions. Conclusions:Among IBD patients receiving long-term treatment of VDZ, the incidence of adverse reactions of VDZ was 72.5%, mainly involving skin, digestive system and respiratory system. Symptomatic treatments could be given, and the prognosis was good. Patients with chronic relapsing clinical type, severe disease activity, combination therapy, and shorter VDZ maintenance injection interval were at higher risk of adverse reactions.

Objective:To observe and analyze the adverse drug reactions (ADRs) caused by adalimumab in patients with inflammatory bowel disease (IBD) and its influencing factors.Methods:A retrospective study was conducted on 106 patients with inflammatory bowel disease treated with adalimumab at Tianjin Medical University General Hospital from November 2019 to November 2023. Among them, 31 patients who experienced adverse reactions were included in the ADR group (case group), while 75 patients who did not experience adverse reactions were included in the non-ADR group (control group). Patients' basic information, laboratory tests, adverse drug reactions, etc were collected. Measurement data with normal distribution were expressed as xˉ± s and means between two groups were compared using independent samples t-test. The percentage of count data was calculated, and the rate between groups was compared by χ2 test. The risk factors of adverse drug reactions caused by adalimumab in patients with inflammatory bowel disease were analyzed by single factor screening and multivariable Logistic regression model. Results:ADR occurred in 31 of 106 patients, accounting for 29.25% (31/106), among those patients which infection was the most common,accounting for 18.87%(20/106). The number of combined drugs (≥3 kinds), drug allergy history, drug duration (≥3 months), blood concentration (>12 μg/mL) in ADR group were higher than those in non-ADR group ( χ2-values were 5.90, 5.78, 6.94 and 10.07, respectively,t-values were 8.55 and 0.97 respectively; all P<0.05). Multivariate Logistic regression results showed that the number of combined drugs ≥3, drug allergy history, drug duration >3 months, blood concentration >12 ng/L, creatinine and total bilirubin levels were all risk factors for adverse drug reactions of adalimumab in IBD patients (O R values were 2.680, 2.394, 3.228, 4.415, 3.673 and 4.646, respectively;95% CI:1.563~3.798, 1.434-3.354, 2.070-4.387, 3.803-5.027, 2.364-4.982 and 3.449-5.843, respectively; all P<0.05). Conclusion:The number of combined drugs ≥3, drug allergy history, drug duration >3 months, blood concentration >12 ng/L, creatinine and total bilirubin levels are all risk factors for adverse drug reactions in IBD patients with adalimumab. In clinical practice, it is necessary to strengthen monitoring and take timely preventive measures for IBD patients with the above-mentioned factors, in order to reduce the incidence of ADR.

Objective:To determine the value of colonoscopy in the diagnosis and treatment of patients with immune checkpoint inhibitor-induced colitis.Methods:Patients who developed colitis and underwent colonoscopy after receiving immune checkpoint inhibitors(ICIs)therapy at Tianjin Medical University General Hospital between December 2020 and December 2023 were reviewed,according to the guidelines of the Chinese Society of Clinical Oncology for the management of ICI-related toxicity.The effect of the treatment and the rela-tionship between prognosis and the pathological features of colonoscopy were analyzed.Results:Patients with ICI-associated colitis who un-derwent colonoscopy had a more than 3 degrees diarrhea,and diffused inflammatory features such as mucosal erythema,exudate,erosion,loss of vascular markings,and edema were observed under the microscope,and the presence of ulcers greater than 1 cm in diameter and/or more than 2 mm deep indicate a poor prognosis for enteritis.Histopathological studies showed changes in glandular structures,such as cryptitis and crypt abscess.The pathological colonoscopic manifestations of patients with microscopic enteritis were inconsistent,and more deep samples should have been taken.Conclusions:The toxicity grading of ICI-associated colitis is not limited to clinical manifestations,but refers to the multi-dimensional analysis of colonoscopic features and histopathological characteristics.Soft colonoscopy can be used as an important follow-up method for patients with colitis,owing to its ease of operation and good tolerance.

OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.

The risks of tumors in patients with inflammatory bowel disease (IBD) are significantly higher than that in normal people. It is still obscure whether anti-tumor necrosis factor (anti-TNF) agents increase the risks of malignant tumors in these patients and whether the patients with previous history of malignant tumors could use anti-TNF agents. It becomes an important issue for making clinical decisions.

The risks of tumors in patients with inflammatory bowel disease (IBD) are significantly higher than that in normal people. It is still obscure whether anti-tumor necrosis factor (anti-TNF) agents increase the risks of malignant tumors in these patients and whether the patients with previous history of malignant tumors could use anti-TNF agents. It becomes an important issue for making clinical decisions.

Objective To investigate the effects of intestinal microbiota of patients with chronic constipation on the expression of serotonin transporter (SERT) and the bowel movement in mice.Methods Fecal samples of patients with slow transit constipation met Rome Ⅲ criteria and healthy normal controls were collected and made into fecal microbiota solution.Twenty specfic pathogen free (SPF) mice were divided into experiment group and control group.The mice of two groups were both pre-treated with streptomycin to establish the germ-free mice model.The mice of control group were gavaged with mixed fecal microbiota solution of healthy normal controls and the mice of experiment group were gavaged with mixed fecal microbiota solution of patients with chronic constipation.Mice were sacrificed after fed for 15 days.Defecation parameters and ink discharge time of mice were detected.The expressions of SERT mRNA and SERT protein in mice intestinal tissues were detected with real time-polymerase chain reaction and Western blotting.The 5-hydroxytryptamine (5-HT) levels of mice intestinal tissues were evaluated by enzyme-linked immunosorbent assay (ELISA) and double immunofluorescent staining.The methods of t test and Chi-square test were performed for statistical analysis.Results On the 15th day,the total number of the feces within 2 h of the experiment group and control group was 8.55±1.83 and 12.14±2.90,respectively,and the difference was statistically significant (t=3.33,P＜0.05).The weight of feces were (151.90 ± 32.42) mg and (246.72 ± 64.01) mg,respectively,and the difference was statistically significant (t=4.18,P＜0.01).The dry weight of feces were (65.52±11.76) mg and (92.93±23.07) mg,respectively,and the difference was statistically significant (t=3.37,P＜0.05).The water content of feces were (56.63 ± 3.01) ％ and (61.95 ± 3.70) ％,respectively,and the difference was statistically significant (t=3.57,P＜0.05).The defecating time of first black feces of the experiment group and control group were (83.24±11.31) min and (69.06±2.72) min,respectively,and the difference was statistically significant (t=-2.74,P＜0.05).The expressions of SERT mRNA and SERT protein levels in mice intestine tissues of the experiment group were significantly higher than those of the control group (t =2.61,-6.89;both P＜0.05).5-HT level of mice intestinal tissues of the experimental group and control group were (151.69± 10.18) ng/mL and (198.77 ± 25.99) ng/mL,respectively,and the difference was statistically significant (t=-4.13,P＜0.01).Conclusion Intestinal microbiota of patients with chronic constipation may influence the expression of SERT in the mice intestinal tissues,and then decrease the level of 5-HT,slowing the bowel movement in mice.