1.Protective effect of dulaglutide on lipopolysaccharide- induced MLE-12 cells
Xingyu Fan ; Hao Duan ; Jie Yan ; Yue Wang ; Yijun Du ; Tianrong Pan ; Xing Zhong
Acta Universitatis Medicinalis Anhui 2025;60(8):1439-1444
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.
2.Evaluation of Renal Function and Oxygenation Levels in Patients with Type 2Diabetes by BOLD MRI
Limin ZHAI ; Deyuan ZHANG ; Tianrong PAN
Journal of Medical Research 2025;54(4):64-68
Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P<0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P<0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P<0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P<0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.
3.Evaluation of Renal Function and Oxygenation Levels in Patients with Type 2Diabetes by BOLD MRI
Limin ZHAI ; Deyuan ZHANG ; Tianrong PAN
Journal of Medical Research 2025;54(4):64-68
Objective To evaluate the relationship between renal function and renal tissue oxygenation in type 2diabetes patients with blood oxygenation level dependent MRI(BOLD MRI)and to explore its value in clinical and scientific research.Methods A total of 80diabetic kidney disease patients with type 2diabetes admitted to hospital from April 2023 to August 2024 were selected.According to the the ratio of urinary albumin and creatinine,the patients were divided into normal albuminuria group,microalbuminuria group and mac-roalbuminuria group.All patients were examined by BOLD MRI.R2* values of renal cortex and medulla were measured by two radiolo-gists respectively,and the mean R2*values of renal cortex and medulla,the ratio of the two values(MCR)were obtained.The consis-tency of CR2* and MR2* measured by 2 physicians and the differences of CR2*,MR2* and MCR among 3 groups were compared,and the correlation with clinical indicators were analyzed.Results There were statistically significant differences in serum creatinine and glomerular filtration rate among the three groups(P<0.05).ACR,urinary microalbumin and urinary N-acetyl-β-D glucosaminase(UANG)were significantly different among the three groups(all P<0.01).The fasting C-peptide based insulin resistance index(HOMA2-IR)of the three groups was significantly different(P<0.05).BOLD MRI results showed that the differences of CR2*,MR2* and MCR among the three groups were statistically significant(all P<0.05).Correlation analysis showed that CR2* and MR2* were positively correlated with creatinine,ACR,urinary microalbumin,UANG and HOMA2-IR,respectively,and negatively correlated with glomerular filtration rate.Conclusion BOLD MRI is a non-invasive method to evaluate oxygenation in diabetic nephrop-athy,and the R2* of cortex and medulla in renal tissue are correlated with different renal function indicators.
4.Study on correlation between time within glucose target range and left ventricular mass index in patients with type 2 diabetes mellitus complicating hypertension
Bo YAN ; Yuan YAO ; Xing ZHONG ; Tianrong PAN
Chongqing Medicine 2024;53(12):1823-1827
Objective To investigate the correlation between the glucose time in range(TIR)and left ventricular mass index(LVMI)in the patients with type 2 diabetes mellitus(T2DM)complicating hyperten-sion.Methods A total of 102 inpatients with T2DM in the Mingguang Municipal People's Hospital from January to December 2022 were selected as the study subjects and conducted the continuous dynamic glucose monitoring.They were divided into the group A(TIR≤40%,n=31),group B(TIR>40%-70%,n=41)and group C(TIR>70%,n=30)according to the TIR level.The clinical data,laboratory indicators and echo-cardiographic parameters were collected and compared among the three groups.Results Compared with the group A,the age,disease course,systolic blood pressure and the levels of HbA1c,FPG,SCr and TG in the group C were significantly decreased,the HDL-C level was increased,and the differences were statistically sig-nificant(P<0.05).Compared with the group B,the age and the levels of SCr,TG,HDL-C,HbA1c and FPG in the group C were decreased,and the differences were statistically significant(P<0.05).Compared with the group A and group B,LAD,LVPW,IVS and LVMI in the group C were reduced with statistical differences(P<0.05).The multiple linear stepwise regression analysis results showed that TIR was a protective factor for LVMI(OR=0.562,95%CI 0.413-0.673,P<0.05),and the disease course and systolic blood pressure were the risk factors(OR=1.511,95%CI:1.067-2.947;OR=2.325,95%CI:1.086-5.574,P<0.05).Conclusion TIR in the patients with T2DM complicating hypertension is correlated with LVMI,and the TIR level may be an influencing factor for early cardiovascular events.
5.Correlation of sarcopenia and osteoporosis in postmenopausal elderly patients with type 2 diabetes
Ping ZHANG ; Yijun DU ; Yue WANG ; Yanqiu WANG ; Xiaoqun XU ; Tianrong PAN
Acta Universitatis Medicinalis Anhui 2024;59(10):1871-1874,1880
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.
6.The effect of sodium-glucose co-transporter 2 inhibitor dapagliflozin on cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus and related factors
Jingcheng DING ; Ying SUN ; Yanyun GUO ; Hong SU ; Yijun DU ; Tianrong PAN ; Xing ZHONG
Chinese Journal of Endocrinology and Metabolism 2023;39(9):772-777
Objective:To investigate the effect of dapagliflozin on cognitive function in middle-aged and elderly type 2 diabetes mellitus patients and related factors.Methods:This was a retrospective study. A total of 200 patients who were hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited randomly. They were divided into the dapagliflozin group and control group. Clinical data were collected; plasma levels of β-amyloid protein(Aβ) 40 and Aβ42 were measured. The Montreal cognitive assessment(MoCA) and the mini-mental state examination(MMSE) were employed to assess cognitive function in both groups. Based on MoCA scores, patients in the dapagliflozin group were further categorized into mild cognitive impairment(MCI) and non-MCI subgroups. Differences among groups were analyzed and compared using t-test, χ2 test, and Mann-Whitney U test, and multivariable logistic regression was used to identify relevant factors associated with cognitive impairment in diabetes patients. Results:Compared to the control group, the dapagliflozin group exhibited significant increases in MMSE and MoCA scores, estimated glomerular filtration rate, and plasma concentration Aβ40(all P<0.05); And the incidence of MCI, homeostasis model assessment for insulin resistance(HOMA-IR), total cholesterol, triglycerides, urine albumin creatine ratio, plasma Aβ42, and Aβ42/Aβ40 ratio were significantly decreased(all P<0.05). Compared with the MCI subgroup, duration of dapagliflozin treatment in the non-MCI subgroup were significantly increased( P<0.05); There were statistically significant decreased in the non-MCI subgroup in age, systolic blood pressure, fasting plasma C-peptide, and HOMA-IR(all P<0.05). Multivariable logistic regression analysis showed that duration of dapagliflozin treatment was a protective factor for cognitive dysfunction( OR=0.322, 95% CI 0.150-0.692, P=0.004) and the age and HOMA-IR were risk factors( OR=1.109, 95% CI 1.014-1.212, P=0.023; OR=3.376, 95% CI 1.276-8.931, P=0.014). Conclusion:Dapagliflozin may improve cognitive function and significantly reduce the incidence of MCI in middle-aged and elderly patients with type 2 diabetes mellitus, possibly associated with the improvement of insulin resistance.
7.Protective effect of dulaglutide against sepsis⁃induced acute kidney inj ury in mice
Fengyi Deng ; Yue Wang ; Xingyu Fan ; Hujing Deng ; Xing Zhong ; Yijun Du ; Hong Su ; Tianrong Pan
Acta Universitatis Medicinalis Anhui 2023;58(8):1329-1334
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.
8.Association between transcription KCNQ1 rs2237892 polymorphism and development of type 2 diabetes in Hefei
Acta Universitatis Medicinalis Anhui 2018;53(1):110-113
Objective To explore the relationship of KCNQ1 rs2237892 polymorphism with type 2 diabetes mellitus(T2DM) in Hefei. Methods A total of 104 healthy individual(control group) and 84 patients with T2DM(T2DM group) were enrolled. The rs2237892 polymorphism KCNQ1 gene was detected by PCR-RFLP. The genetype, allele frequency, related clinical and biochemical data were compared between the two groups. Results There were no significant differences in alleles or genotype frequencies of KCNQ1 rs2237892 gene among control group and T2DM group. The result of Logistic regression analysis showed that the risk of T2DM in the subjects with CT genetype of rs2237892 was 1. 44 times of those with CC genotype(OR =1.44, 95% CI: 1. 06 ~ 1. 95, P=0. 02). Conclusion KCNQ1 rs2237892 gene may be the susceptibility gene of T2DM in Hefei.
9.Effect of Exenatide therapy in type 2diabetes with nonalcoholic fatty liver disease
Yueshuang HU ; Xing ZHONG ; Tianrong PAN
Acta Universitatis Medicinalis Anhui 2017;52(4):546-549
Objective To observe the therapeutic effect of exenatide combined with metformin therapy in type 2 diabetes with nonalcoholic fatty liver disease.Methods 50 patients with type 2 diabetes and nonalcoholic fatty liver disease were randomly divided into experimental group and control group with 25 cases in each.The control group were treated with metformin, the experimental group were treated with exenatide on the basis of metformin.Before treatment and at the end of 12-week treatment, patients height, weight, body mass index(BMI), waistline(WC), glycated hemoglobin(HbA1c), fasting blood glucose(FBG),fasting C-peptide(FCP), triglyceride(TG), cholesterol(TCH), high density lipoprotein(HDL), low density lipoprotein(LDL),systolic pressure(SBP), diastolic pressure(DBP), alanine aminotransferase(ALT), superoxide dismutase(SOD), liver lipid contents(LFC) were detected.Results Baseline data were not significantly different between the two groups.Compared to baseline, WC, HbA1c, FBG and LFC in experimental group and control group were obviously improved after treatment(P<0.05), and the experimental group improved more significantly than control group(P<0.05).Conclusion Exenatide combined with metformin has an obvious therapeutic effect on BMI, WC, HbA1c, FBG, FCP, SBP, TG, TCH, HDL, LDL, LFC than mere metformin treatment in treatment of type 2 diabetes with nonalcoholic fatty liver disease.
10.Change of IL-23/IL-17 axis in peripheral blood of patients with Graves disease treated by I or antithyroid drugs therapy
Ming YANG ; Tianrong PAN ; Xing ZHONG
Acta Universitatis Medicinalis Anhui 2017;52(11):1718-1720,1725
Objective To detect the expression level of interleukin-17 (IL-17)/interleukin-23 (IL-23) axis in peripheral blood of patients with Graves disease (GD) before and after 131I or antithyroid drugs (ATD) treatment.Methods The study groups included 40 patients with incipient GD(GD group),20 of whom were treated by 131 I,others were treated by ATD.Forty sex and age matched healthy subjects were recruited as control group.ELISA was uesed to detect interleukin-17 (IL-17),interleukin-23 (IL-23) level before and after the treatment of the GD group and control group.Results ① The expression of IL-23,IL-17 in GD group was significantly higher than the control group(P <0.05);②6 months after 131I treatment,the level of serum IL-23,IL-17 were significantly lower than before (P < 0.05),but still higher than the control group (P < 0.05),which was not found in ATD treatment group.Conclusion IL-23/IL-17 axis may play a role in GD which may also be relevant to 131I treatment.


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