Objective: To investigate the protective effect of dulaglutide on lipopolysaccharide (LPS)-induced inju- ry in MLE-12 cells. Methods: An in vitro model of acute lung injury was established by inducing MLE-12 cells with LPS ( 1 μg/mL) , followed by treatment with dulaglutide for 24 hours. The cells were divided into four groups : CON group , LPS group , LPS + 100 nmol/L dulaglutide group , and LPS + 200 nmol/L dulaglutide group. Protein and RNA were extracted from each group. The mRNA levels of inflammatory factors , including interleukin (IL)-6 , tumor necrosis factor-α (TNF-α ) , IL-1β , monocyte chemotactic protein 1 (CCL2) , C-X-C motif chemokine lig- and (CXCL) 1 and CXCL2 , were detected by qRT-PCR. Cell apoptosis was assessed by TUNEL assay , and the expression levels of phosphorylated protein kinase B (P-Akt) and phosphorylated extracellular signal-regulated ki- nase (P-Erk) were measured by Western blot. Results: Compared with the CON group , the LPS group showed in- creased mRNA levels of inflammatory mediators (TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2) , increased TUNEL-positive cells , and elevated expression of P-Akt and P-Erk proteins. Compared with the LPS group , the LPS + 100 nmol/L dulaglutide treatment group exhibited reduced mRNA levels of TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2 , decreased TUNEL-positive cells , and downregulated expression of P-Akt and P-Erk pro- teins. However, the LPS + 200 nmol/L dulaglutide treatment group showed less pronounced improvement in inflam- matory factors compared to the LPS + 100 nmol/L dulaglutide group. Conclusion Dulaglutide has a protective effect on LPS-induced injury in MLE-12 cells , potentially through inhibiting Akt and Erk phosphorylation , thereby reducing the expression of inflammatory mediators and alleviating inflammatory damage , ultimately protecting the lungs.

Objective To investigate the correlation between the appendicular skeletal mass index(ASMI)and os-teoporosis(OP)in postmenopausal patients with type 2 diabetes(T2DM).Methods 164 hospitalized postmeno-pausal elderly T2DM patients were selected and their bone density(BMD)and appendicular skeletal mass were measured using dual energy X-ray absorption method(DXA).ASMI=appendicular skeletal mass/height2(kg/m2),and they were divided into OP group and non OP group based on T value.The general clinical data,blood biochemical indicators,and ASMI between the two groups were compared,and Logistic regression analysis,ROC curve were further used to analyze the correlation and diagnostic power.Results Compared with non OP group,OP group had a higher incidence of sarcopenia(SAC)(P＜0.05);the differences in age,ASMI,body mass index(BMI),and estradiol(E2)had significant differences between the two groups(P＜0.05);Logistic regression analysis showed that the reduction of ASMI[OR=0.133,95％CI(0.029-0.611)],BMI[OR=0.785,95％CI(0.625-0.985)],and E2[OR=0.967,95％CI(0.942-0.993)]were protective factors for OP;receiver operating curve(ROC)suggested that the AUC of ASMI for OP prediction was 0.752[95％CI(0.632-0.872),P＜0.001]with sensitivity 87.5％,specificity 47.8％,and the best diagnostic value was 5.52 kg/m2.Conclusion The reduction of ASMI,BMI,and E2 is positively correlated with the occurrence of osteoporosis.ASMI is an important protective factor for osteoporosis.Early OP screening and risk factor assessment should be conducted for elderly postmenopausal T2DM patients,and early intervention measures should be taken to reduce the risk of falls and fractures.

Objective : To investigate the protective effect of dulaglutide on acute kidney injury (AKI) induced by lipopolysaccharide (LPS) . Methods : Twenty⁃four male C57BL/6 mice were randomly divided into Control group (normal saline) , LPS group (LPS 15 mg/kg) , LPS + Dul group (LPS 15 mg/kg + Dulaglutide 0. 6 mg/kg) and Dul group (Dulaglutide 0. 6 mg/kg) with 6 mice in each group. The drug was administered by intraperitoneal injection. After drug intervention for 24 h , the body weight and kidney weight of mice were recorded , and kidney tissue and serum samples were collected. The pathological changes in kidney tissue were observed by HE staining. The serum urea nitrogen (BUN) and creatinine (CRE) levels were detected by the kit. The levels of cytokines interleukin (IL⁃6) , tumor necrosis factor (TNF⁃α ) and IL⁃1β in the kidney were detected by qRT⁃PCR. The contents of macrophage marker F4/80 and myeloperoxidase (MPO) in kidney were determined by immunohistochemistry. Results : Compared with Control group , mice in LPS group lost weight and increased kidney weight ( P < 0. 001) . Moreover, the levels of BUN and CRE increased (P < 0. 001 , P < 0. 01) . Meanwhile , the mRNA levels of IL⁃6 , IL⁃1β and TNF⁃α increased (P < 0. 05) . There was obvious pathological damage in kidney tissue. In addition , macrophage and neutrophil infiltration increased in LPS group ( P < 0. 001) . Compared with LPS group , mice in LPS + Dul group gained weight and lost kidney weight (P < 0. 05 , P < 0. 001) . Moreover, the levels of BUN and CRE in LPS + Dul group decreased (P < 0. 01) . The renal histological scores were reduced (P < 0. 05) . In addition , the levels of IL⁃6 , IL⁃1β and TNF⁃α in kidney tissue decreased (P < 0. 05 or P < 0. 01) . Moreover, the infiltration of macrophages and neutrophils in kidney was reduced (P < 0. 01) . Conclusion Dulaglutide has a protective effect on LPS⁃induced sepsis AKI , which may be related to reduce the expression of inflammatory media⁃ tors and decrease the infiltration of inflammatory cell.

Objective To explore the application effect of high-functioning group therapy model in female patients with depression.Methods A total of 80 female patients with depression who were hospitalized in the Department of Psychiatry,the Second Affiliated Hospital of Xinxiang Medical University from April 2021 to April 2022 were selected as the research sub-jects.According to the treatment methods,the patients were divided into the observation group and the control group,with 40 patients in each group.The patients in the two groups were treated with routine anti-depressant drugs based on their condition;the patients in the control group received routine nursing interventions based on their condition;the patients in the observation group received high-function group therapy intervention on the basis of the control group;the patients in the two groups were in-tervened for 1 month.Before and one month after the intervention,the levels of depression and anxiety of patients in the two groups were evaluated by the Hamilton depression scale(HAMD)and the Hamilton anxiety scale(HAMA);the quality of life of patients in the two groups was evaluated by the World Health Organization's quality of life scale(WHOQOL-BREF),while the interpersonal relationships of patients in the two groups were evaluated by the interpersonal relationships comprehensive diagnostic scale.Results Before intervention,there was no statistically significant difference in the scores of HAMA,HAMD,WHOQOL-BREF and interpersonal relationship comprehensive diagnostic scale of patients between the two groups(P＞0.05).The HAMA and HAMD scores of patients in the two groups after one month of intervention were significantly lower than those before intervention(P＜0.05);after one month of intervention,the HAMA and HAMD scores of patients in the observa-tion group were significantly lower than those in the control group(P＜0.05).The WHOQOL-BREF scores in the social,psychological,physiological and environmental domains of patients after one month of intervention were significantly higher than those before intervention in the two groups(P＜0.05);after one month of intervention,the WHOQOL-BREF scores in the social,psychological,physiological and environmental domains of patients in the observation group were significantly higher than those in the control group(P＜0.05).The scores of interpersonal interaction,conversation,social interaction and hetero-sexual interaction and total scores of interpersonal relationship comprehensive diagnosis scale of patients one month of interven-tion were significantly lower than those before intervention in the two groups after(P＜0.05);after one month of intervention,the scores of interpersonal interaction,conversation,social interaction and heterosexual interaction and total scores of interper-sonal relationship comprehensive diagnosis scale of patients in the observation group were significantly lower than those in the control group(P＜0.05).Conclusion Compared to conventional nursing interventions,the high-functioning group therapy model can significantly reduce the depression and anxiety of female depression patients,improve interpersonal communication skills and their quality of life.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.

Objective:To assess the short-term efficacy and safety of tacrolimus in patients with refractory Crohn′s disease (CD) , and analyze the influencing factors of clinical response.Methods:A single center restrospective cohort study was conducted. The clinical data of patients with refractory CD in Renji Hospital of Shanghai Jiaotong University School of Medicine from March 2014 to June 2019 were analyzed retrospectively. The patients received tacrolimus treatment for at least 3 months. Clinical response, clinical remission and relapse after tacrolimus treatment were evaluated by Crohn′s disease activity index (CDAI) . According to the existence of clinical response after 3 months of tacrolimus treatment, the patients were divided into clinical response group and non-clinical response group. The differences in clinical data between the 2 groups were assessed by univariate analysis. The variables with P<0.1 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of clinical response. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of risk factors in predicting the clinical response of tacrolimus for the treatment of refractory CD. Results:A total of 45 patients with refractory CD were included, including 31 males and 14 females with the age of 32 (27, 39) years old. The disease duration was 61.0 (28.0, 97.5) months. The CDAI was 203 (175, 229) points before the treatment of tacrolimus while it decreased to 137 (117, 175) points after the treatment of tacrolimus for 3 months, and the difference was significant ( Z = -5.512, P<0.01) . After the treatment of tacrolimus for 3 months, 13 patients (28.9%) with clinical response were set as clinical response group and 32 (71.1%) without clinical response were set as non-clinical response group. Univariate analysis showed that the differences in gender, CDAI before the treatment of tacrolimus and neutrophil-to-lymphocyte ratio (NLR) between the clinical response group and non-clinical response group were statistically significant (all P<0.05) . Gender, CDAI before the treatment of tacrolimus and NLR were included for the multivariate Logistic regression analysis. The results showed that CDAI ( OR = 1.026, 95% CI: 1.006-1.046, P = 0.012) and NLR ( OR = 2.605, 95% CI: 1.290-5.258, P = 0.008) were the independent risk factors for predicting clinical response. The areas under ROC curve of CDAI, NLR and NLR combined with CDAI in predicting clinical response of tacrolimus in patients with refractory CD were 0.786 (95% CI : 0.648-0.924) , 0.764 (95% CI: 0.595-0.934) and 0.861 (95% CI : 0.729-0.992) , the optimal cut-off values were 189.15, 2.82 and 0.31, sensitivities were 100%, 84.6% and 84.6%, and specificities were 53.1%, 71.9% and 84.4%, respectively. Twenty-six patients continued to receive tacrolimus for 12 months, and the clinical remission rate was 73.1% (19/26) and the recurrence rate was 26.9% (7/26) . Forty-five patients were followed up for 1 year, adverse effects occurred in 6 and there was no severe adverse effects during the treatment of tacrolimus. Conclusions:Tacrolimus can be used as an immunosuppressant to induce the remission and maintenance in refractory CD patients. CDAI and NLR can be used as independent indicators to predict the clinical response of tacrolimus in the treatment of patients with refractory CD, and the combination of CDAI and NLR has higher prediction efficiency.

Objective:To assess the short-term efficacy and safety of tacrolimus in patients with refractory Crohn′s disease (CD) , and analyze the influencing factors of clinical response.Methods:A single center restrospective cohort study was conducted. The clinical data of patients with refractory CD in Renji Hospital of Shanghai Jiaotong University School of Medicine from March 2014 to June 2019 were analyzed retrospectively. The patients received tacrolimus treatment for at least 3 months. Clinical response, clinical remission and relapse after tacrolimus treatment were evaluated by Crohn′s disease activity index (CDAI) . According to the existence of clinical response after 3 months of tacrolimus treatment, the patients were divided into clinical response group and non-clinical response group. The differences in clinical data between the 2 groups were assessed by univariate analysis. The variables with P<0.1 in univariate analysis and having clinical significance were further analyzed by multivariate Logistic regression to determine the independent risk factors of clinical response. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of risk factors in predicting the clinical response of tacrolimus for the treatment of refractory CD. Results:A total of 45 patients with refractory CD were included, including 31 males and 14 females with the age of 32 (27, 39) years old. The disease duration was 61.0 (28.0, 97.5) months. The CDAI was 203 (175, 229) points before the treatment of tacrolimus while it decreased to 137 (117, 175) points after the treatment of tacrolimus for 3 months, and the difference was significant ( Z = -5.512, P<0.01) . After the treatment of tacrolimus for 3 months, 13 patients (28.9%) with clinical response were set as clinical response group and 32 (71.1%) without clinical response were set as non-clinical response group. Univariate analysis showed that the differences in gender, CDAI before the treatment of tacrolimus and neutrophil-to-lymphocyte ratio (NLR) between the clinical response group and non-clinical response group were statistically significant (all P<0.05) . Gender, CDAI before the treatment of tacrolimus and NLR were included for the multivariate Logistic regression analysis. The results showed that CDAI ( OR = 1.026, 95% CI: 1.006-1.046, P = 0.012) and NLR ( OR = 2.605, 95% CI: 1.290-5.258, P = 0.008) were the independent risk factors for predicting clinical response. The areas under ROC curve of CDAI, NLR and NLR combined with CDAI in predicting clinical response of tacrolimus in patients with refractory CD were 0.786 (95% CI : 0.648-0.924) , 0.764 (95% CI: 0.595-0.934) and 0.861 (95% CI : 0.729-0.992) , the optimal cut-off values were 189.15, 2.82 and 0.31, sensitivities were 100%, 84.6% and 84.6%, and specificities were 53.1%, 71.9% and 84.4%, respectively. Twenty-six patients continued to receive tacrolimus for 12 months, and the clinical remission rate was 73.1% (19/26) and the recurrence rate was 26.9% (7/26) . Forty-five patients were followed up for 1 year, adverse effects occurred in 6 and there was no severe adverse effects during the treatment of tacrolimus. Conclusions:Tacrolimus can be used as an immunosuppressant to induce the remission and maintenance in refractory CD patients. CDAI and NLR can be used as independent indicators to predict the clinical response of tacrolimus in the treatment of patients with refractory CD, and the combination of CDAI and NLR has higher prediction efficiency.

Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.