Objective:To explore the correlation between bile acid profiles and early efficacy of biologics for Crohn's disease (CD) .Methods:Patients with active CD who were treated with induction therapy with biologics (ustekinumab, vedolizumab, or combination therapy) in outpatient and inpatient clinics from January 2021 to March 2024 in Jinhua Central Hospital were included. Clinical data and serum bile acid profile of patients before treatment were collected. At the end of induction therapy, CD patients were categorized into remission and non-remission groups based on the CD activity index (CDAI) scores. Compare the clinical data of the two groups of patients with CD before induction treatment with biological agents, retrospective analysis of bile acid profiles in relation to early efficacy of biologics.Results:A total of 100 patients with CD were included, including 74 patients in remission group and 26 patients in non-remission group. Univariate analysis showed that hemoglobin [137 (119, 147) g/L vs. 121 (109, 136) g/L, P = 0.027], erythrocyte pressure volume [ (0.40 ± 0.06) % vs. (0.38 ± 0.05) %, P = 0.030], total bile acids[3.8 (2.4, 6.1) μmol/L比2.0 (1.5, 2.7) μmol/L, P < 0.001], cholic acid [0.188 (0.059, 0.597) μmol/L vs. 0.055 (0.024, 0.111) μmol/L, P < 0.001], chenodeoxycholic acid [0.812 (0.268, 1.717) μmol/L vs. 0.308 (0.087, 0.552) μmol/L, P < 0.001], and deoxycholic acid [0.042 (0.001, 0.299) μmol/L vs. 0.002 (0.001, 0.159) μmol/L, P = 0.028] were signficantly higher in remission group than those in unremission group. In addition, the pretreatment endoscopic score (SES-CD) [4.0 (0, 6.0) vs. 6.0 (3.0, 10.5), P = 0.025], erythrocyte sedimentation rate (ESR) [9.0 (2.8, 20.0) mm/1 h vs. 28.0 (12.8, 40.8) mm/1 h, P < 0.001] and C reactive protein (CRP) [0.6 (0.2, 6.7) mg/L vs. 9.1 (1.5, 23.9) mg/L, P < 0.001] in the remission group were lower than those in the non-remission group. Multirariate logistic regression analysis showed that chenodeoxycholic acid ( OR = 3.317, 95% CI: 1.270-12.437; P = 0.041) and ESR ( OR =0.979, 95% CI: 0.957-0.997; P = 0.034) were the independent influencing affecting the efficacy of biologics for the treatment of Crohn's disease in early stage. Conclusion:Chenodeoxycholic acid is an independent influencing factor of early efficacy of biologics for Crohn's disease.

Objective:To explore the correlation between bile acid profiles and early efficacy of biologics for Crohn's disease (CD) .Methods:Patients with active CD who were treated with induction therapy with biologics (ustekinumab, vedolizumab, or combination therapy) in outpatient and inpatient clinics from January 2021 to March 2024 in Jinhua Central Hospital were included. Clinical data and serum bile acid profile of patients before treatment were collected. At the end of induction therapy, CD patients were categorized into remission and non-remission groups based on the CD activity index (CDAI) scores. Compare the clinical data of the two groups of patients with CD before induction treatment with biological agents, retrospective analysis of bile acid profiles in relation to early efficacy of biologics.Results:A total of 100 patients with CD were included, including 74 patients in remission group and 26 patients in non-remission group. Univariate analysis showed that hemoglobin [137 (119, 147) g/L vs. 121 (109, 136) g/L, P = 0.027], erythrocyte pressure volume [ (0.40 ± 0.06) % vs. (0.38 ± 0.05) %, P = 0.030], total bile acids[3.8 (2.4, 6.1) μmol/L比2.0 (1.5, 2.7) μmol/L, P < 0.001], cholic acid [0.188 (0.059, 0.597) μmol/L vs. 0.055 (0.024, 0.111) μmol/L, P < 0.001], chenodeoxycholic acid [0.812 (0.268, 1.717) μmol/L vs. 0.308 (0.087, 0.552) μmol/L, P < 0.001], and deoxycholic acid [0.042 (0.001, 0.299) μmol/L vs. 0.002 (0.001, 0.159) μmol/L, P = 0.028] were signficantly higher in remission group than those in unremission group. In addition, the pretreatment endoscopic score (SES-CD) [4.0 (0, 6.0) vs. 6.0 (3.0, 10.5), P = 0.025], erythrocyte sedimentation rate (ESR) [9.0 (2.8, 20.0) mm/1 h vs. 28.0 (12.8, 40.8) mm/1 h, P < 0.001] and C reactive protein (CRP) [0.6 (0.2, 6.7) mg/L vs. 9.1 (1.5, 23.9) mg/L, P < 0.001] in the remission group were lower than those in the non-remission group. Multirariate logistic regression analysis showed that chenodeoxycholic acid ( OR = 3.317, 95% CI: 1.270-12.437; P = 0.041) and ESR ( OR =0.979, 95% CI: 0.957-0.997; P = 0.034) were the independent influencing affecting the efficacy of biologics for the treatment of Crohn's disease in early stage. Conclusion:Chenodeoxycholic acid is an independent influencing factor of early efficacy of biologics for Crohn's disease.

OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition （EMT） and renal fibrosis in diabetic kidney disease （DKD） model rats. METHODS Eight rats were selected as normal group （ordinary feed）； the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg/kg） to induce the DKD model. Model rats were randomly divided into model group， irbesartan group [positive control， 13.5 mg/（kg·d）] and modified Taohong siwu decoction group [6.48 g/（kg·d）]， with 8 rats in each group. All groups were given relevant medicine intragastrically， once a day， for 16 consecutive weeks. Twenty-four- hour urinary total protein （24 h UTP） was detected at the end of the 4th， 8th， 12th and 16th week of administration. After the last medication， the body mass， water intake， food intake， urine output， the levels of fasting blood glucose， serum creatinine （Scr） and blood urea nitrogen （BUN） as well as mRNA and protein expressions of P-cadherin， nephrin， α -smooth muscle actin （α-SMA）， Wilms’ tumor gene 1 （WT1）， transforming growth factor-β1（ TGF-β1） and type Ⅳ collagen （Col-Ⅳ） in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group， 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend （P＜0.05）； the body weight of rats increased significantly， but the amount of water intake and urine decreased significantly； Scr and BUN level， mRNA expression of α-SMA， mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced， while the mRNA expressions of P-cadherin， nephrin and WT1 were increased significantly （P＜0.05）； the protein deposition of α-SMA was reduced， protein depositions of P-cadherin， nephrin and WT1 were increased； the pathological damage and fibrosis of renal tissue were relieved； the thickness of glomerular basement membrane was decreased significantly （P＜0.05）. CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats， and alleviate renal pathological damage and podocyte damage， thus protecting renal function， and delaying the process of renal fibrosis.

OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition （EMT） and renal fibrosis in diabetic kidney disease （DKD） model rats. METHODS Eight rats were selected as normal group （ordinary feed）； the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg/kg） to induce the DKD model. Model rats were randomly divided into model group， irbesartan group [positive control， 13.5 mg/（kg·d）] and modified Taohong siwu decoction group [6.48 g/（kg·d）]， with 8 rats in each group. All groups were given relevant medicine intragastrically， once a day， for 16 consecutive weeks. Twenty-four- hour urinary total protein （24 h UTP） was detected at the end of the 4th， 8th， 12th and 16th week of administration. After the last medication， the body mass， water intake， food intake， urine output， the levels of fasting blood glucose， serum creatinine （Scr） and blood urea nitrogen （BUN） as well as mRNA and protein expressions of P-cadherin， nephrin， α -smooth muscle actin （α-SMA）， Wilms’ tumor gene 1 （WT1）， transforming growth factor-β1（ TGF-β1） and type Ⅳ collagen （Col-Ⅳ） in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group， 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend （P＜0.05）； the body weight of rats increased significantly， but the amount of water intake and urine decreased significantly； Scr and BUN level， mRNA expression of α-SMA， mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced， while the mRNA expressions of P-cadherin， nephrin and WT1 were increased significantly （P＜0.05）； the protein deposition of α-SMA was reduced， protein depositions of P-cadherin， nephrin and WT1 were increased； the pathological damage and fibrosis of renal tissue were relieved； the thickness of glomerular basement membrane was decreased significantly （P＜0.05）. CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats， and alleviate renal pathological damage and podocyte damage， thus protecting renal function， and delaying the process of renal fibrosis.

OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy （DN）. METHODS Eight rats were selected as control group （ordinary feed）， the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin （35 mg/kg） to induce DN model. Model rats were randomly divided into model group （purified water）， irbesartan group （positive control， 14.12 mg/kg） and Tongxinluo capsule group （0.3 g/kg）， including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically， once a day， for 16 consecutive weeks. After the last medication， fasting blood glucose and 24 h urinary total protein （24 h UTP） were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator （PA） and plasminogen activator inhibitor 1 （PAI-1） were measured. mRNA expressions of transforming growth factor-β（1 TGF-β1）， type Ⅳ collagen（COL-Ⅳ）， Wnt4 and β-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β1， COL-Ⅳ， focal adhesion kinase （FAK）， integrin-linked kinase （ILK）， E-cadherin， PA， PAI-1， Wnt4 and β-catenin in renal cortex of rats were observed or determined. RESULTS Compared with model group， 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced （P＜0.05）； pathological damage and fibrosis of renal cortex were relieved； the expression of PA in serum and renal cortex was significantly increased， while PAI-1 level was significantly reduced （P＜0.05）； the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced， and corresponding mRNA expression was decreased significantly （P＜0.05）； the depositions of ILK and FAK were decreased， while the deposition of E-cadherin was increased； protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced （P＜0.05）. CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats， and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity， the decrease of ILK and FAK expression， and inhibition of Wnt/β-catenin signaling pathway.

Objectives:To explore the association of interleukin-19 gene polymorphisms with susceptibility and clinical phenotypes of Crohn′s disease (CD) . Methods:A retrospective case-control study was conducted. Eighty-three CD patients and 120 healthy people in Jinhua Municipal Central Hospital with matched gender and age as controls were enrolled. Allele and genotype frequencies of interleukin-19 gene rs2243188 and rs2243193 loci were detected by Sanger sequencing. The differences in allele and genotype frequencies of rs2243188 and rs2243193 loci between the two groups were compared, and the association between gene polymorphisms of the above loci and disease phenotype (disease site and disease behavior) and drug efficacy was analyzed. Results:The allelic and genotypic frequencies of the rs2243188 and rs2243193 loci differed between the two groups (all P<0.05) . Compared with control group, genotype CC+CA of rs2243188 frequency was higher in patients with ileocolonic CD (86.67% vs. 60.00%, OR = 4.333, 95% CI: 1.891-9.929, P = 0.001) , allele C of rs2243188 frequencies were higher in patients with terminal ileal CD (44.44% vs. 37.08%, OR = 5.589, 95% CI: 5.378-5.918, P = 0.019) and ileocolonic CD (50.00% vs. 37.08%, OR = 6.589, 95% CI: 6.378-7.918, P = 0.018) . However, genotype GA+AA of rs2243193 frequencies were lower in patients with terminal ileal CD (55.56% vs. 93.33%, OR = 0.089, 95% CI: 0.020-0.399, P = 0.002) and ileocolonic CD (75.00% vs. 93.33%, OR = 0.214, 95% CI: 0.085-0.540, P = 0.001) , allele A of rs2243193 frequencies were lower in patients with terminal ileal CD (50.00% vs. 70.83%, OR = 0.809, 95% CI: 0.724-0.908, P = 0.023) and ileocolonic CD (47.50% vs. 70.83%, OR = 0.132, 95% CI: 0.008-0.502, P = 0.018) . Furthermore, compared with control group, allele C (49.28% vs. 37.08%, OR = 1.607, 95% CI: 1.397-2.927, P = 0.021) and genotype CC+CA (84.06% vs. 60.00%, OR = 3.515, 95% CI: 1.676-7.374, P = 0.001) of rs2243188 frequencies were higher in patients with ileal lesion, allele A (47.83% vs. 70.83%, OR = 0.742, 95% CI: 0.709-1.741, P = 0.015) and genotype GA+AA (72.46% vs. 93.33%, OR = 0.188, 95% CI: 0.077-0.458, P = 0.002) of rs2243193 frequencies were lower in patients with ileal lesion.Compared with control group, allele A (50.00% vs. 70.83%, OR = 0.243, 95% CI: 0.352-0.679, P = 0.014) and genotype GA+AA (66.67% vs. 93.33%, OR = 0.143, 95% CI: 0.030-0.680, P = 0.006) of rs2243193 frequencies were lower in patients with penetrating CD. Moreover, the rs2243188 polymorphisms were not associated with disease behavior (all P>0.05) , the rs2243188 and rs2243193 polymorphisms were not associated with the efficacy of corticosteroid and infliximab (all P>0.05) . Conclusions:The gene mutation of the interleukin-19 gene rs2243188 locus may contribute to an increased risk for the CD with ileal lesions. But the gene mutation of rs2243193 locus may contribute to an decreased risk for CD with ileal lesions and penetrating CD.

Objectives:To explore the association of interleukin-19 gene polymorphisms with susceptibility and clinical phenotypes of Crohn′s disease (CD) . Methods:A retrospective case-control study was conducted. Eighty-three CD patients and 120 healthy people in Jinhua Municipal Central Hospital with matched gender and age as controls were enrolled. Allele and genotype frequencies of interleukin-19 gene rs2243188 and rs2243193 loci were detected by Sanger sequencing. The differences in allele and genotype frequencies of rs2243188 and rs2243193 loci between the two groups were compared, and the association between gene polymorphisms of the above loci and disease phenotype (disease site and disease behavior) and drug efficacy was analyzed. Results:The allelic and genotypic frequencies of the rs2243188 and rs2243193 loci differed between the two groups (all P<0.05) . Compared with control group, genotype CC+CA of rs2243188 frequency was higher in patients with ileocolonic CD (86.67% vs. 60.00%, OR = 4.333, 95% CI: 1.891-9.929, P = 0.001) , allele C of rs2243188 frequencies were higher in patients with terminal ileal CD (44.44% vs. 37.08%, OR = 5.589, 95% CI: 5.378-5.918, P = 0.019) and ileocolonic CD (50.00% vs. 37.08%, OR = 6.589, 95% CI: 6.378-7.918, P = 0.018) . However, genotype GA+AA of rs2243193 frequencies were lower in patients with terminal ileal CD (55.56% vs. 93.33%, OR = 0.089, 95% CI: 0.020-0.399, P = 0.002) and ileocolonic CD (75.00% vs. 93.33%, OR = 0.214, 95% CI: 0.085-0.540, P = 0.001) , allele A of rs2243193 frequencies were lower in patients with terminal ileal CD (50.00% vs. 70.83%, OR = 0.809, 95% CI: 0.724-0.908, P = 0.023) and ileocolonic CD (47.50% vs. 70.83%, OR = 0.132, 95% CI: 0.008-0.502, P = 0.018) . Furthermore, compared with control group, allele C (49.28% vs. 37.08%, OR = 1.607, 95% CI: 1.397-2.927, P = 0.021) and genotype CC+CA (84.06% vs. 60.00%, OR = 3.515, 95% CI: 1.676-7.374, P = 0.001) of rs2243188 frequencies were higher in patients with ileal lesion, allele A (47.83% vs. 70.83%, OR = 0.742, 95% CI: 0.709-1.741, P = 0.015) and genotype GA+AA (72.46% vs. 93.33%, OR = 0.188, 95% CI: 0.077-0.458, P = 0.002) of rs2243193 frequencies were lower in patients with ileal lesion.Compared with control group, allele A (50.00% vs. 70.83%, OR = 0.243, 95% CI: 0.352-0.679, P = 0.014) and genotype GA+AA (66.67% vs. 93.33%, OR = 0.143, 95% CI: 0.030-0.680, P = 0.006) of rs2243193 frequencies were lower in patients with penetrating CD. Moreover, the rs2243188 polymorphisms were not associated with disease behavior (all P>0.05) , the rs2243188 and rs2243193 polymorphisms were not associated with the efficacy of corticosteroid and infliximab (all P>0.05) . Conclusions:The gene mutation of the interleukin-19 gene rs2243188 locus may contribute to an increased risk for the CD with ileal lesions. But the gene mutation of rs2243193 locus may contribute to an decreased risk for CD with ileal lesions and penetrating CD.

Objective To study the correlation between vitamin D receptor (VDR) gene polymorphism and the risk of colorectal cancer.Methods Three hundred and fifty patients with colorectal cancer treated in our hospital from May 2013 to August 2016 were randomly selected as the study group,and 350 healthy subjects were recruited in this study.The genomic DNA was extracted from peripheral blood of all subjects.Twenty-nine VDR single nucleotide polymorphisms (SNPs) were selected and genotyped,and the plasma vitamin D concentration was measured.Logistic regression model was used to evaluate the odds ratio (OR) and 95％ confidence interval (CI) of colorectal cancer.Results Rs2254210,rs1540339,rs2107301,rs11168267,rs11574113,rs731236,rs3847987 and rs11574143 VDR SNPs were associated with the risk of colorectal cancer (P ＜ 0.05),and the risk of colorectal cancer was significantly higher than that of colorectal cancer (P ＜ 0.05).The SNPs of rs11574113,rs3847987 and rs11574143 were more correlated with the risk of colorectal cancer in people with higher plasma vitamin D concentrations.There was a significant difference in the proportion of patients with genotype at different levels of plasma vitamin D in the rs7968585 locus (P ＜ 0.05).Conclusion The polymorphism of vitamin D receptor gene has a certain correlation with the risk of colorectal cancer,and the detection of vitamin D gene polymorphism has a certain significance for predicting the occurrence of colorectal cancer and guiding clinical medicine.

OBJECTIVETo assess the association of inflammatory bowel disease with polymorphisms and haplotypes of Fucosyltransferase 3 (FUT3) gene.

METHODSA total of 389 patients with ulcerative colitis (UC), 274 patients with Crohn's disease (CD), and 492 controls were collected. Three single nucleotide polymorphisms (SNPs) of the FUT3 gene (rs28362459, rs3745635 and rs3894326) were determined by direct sequencing. Linkage disequilibrium and haplotype analysis were performed using a Haploview 4.2 software.

RESULTSCompared with the controls, the allele and genotype distributions of FUT3 gene did not significantly differ between the UC and CD groups (all P>0.05). By stratified analysis, the mutant allele (A) and genotype (GA+AA) of the FUT3 gene (rs3745635) were significantly increased in the UC group with distal colitis compared with the controls (P<0.01, P<0.05, respectively). The mutant allele (G) and genotype (TG+GG) of the FUT3 gene (rs28362459) as well as the mutant allele (A) of FUT3(rs3745635) were significantly increased in patients with ileocolonic CD and ileal CD as compared with the controls (P<0.05, P<0.01, P<0.05, respectively). The frequency of mutant allele (G) of FUT3(rs28362459) was higher in stricturing CD patients than in the controls (P<0.05). In addition, the three polymorphic loci of FUT3 gene were shown in complete linkage disequilibrium [rs3894326/rs3745635 (D'=1.0, r2=0.017), rs3894326/rs28362459 (D'=0.937, r2=0.311), rs3745635/rs28362459 (D'=0.944, r2=0.448)]. However, the frequency of each haplotype was not significantly different between the UC and CD groups compared with the controls (all P>0.05).

CONCLUSIONFUT3 (rs3745635) mutation may increase the risk of distal colitis. FUT3 (rs28362459 and rs3745635) mutations may engender the increased risk of ileocolonic and ileal CD. Moreover, FUT3 (rs28362459) polymorphism may influence the incidence of stricturing CD.

Adult ; Alleles ; Colitis, Ulcerative ; enzymology ; genetics ; Crohn Disease ; enzymology ; genetics ; Female ; Fucosyltransferases ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Haplotypes ; Humans ; Inflammatory Bowel Diseases ; enzymology ; genetics ; Linkage Disequilibrium ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Young Adult

objective To observe the effects of megsin gene transfection on glomerular mesangial cells(GMCs)and the expression of platelet-derived growth factor-BB(PDGF-BB),phosphorylated extracellular signal-regulated protein kinase(pERK1/2),transforming growth factor β1 (TGF-β1)and type Ⅳ collagen under high concentration of glucose,and to investigate the impact of megsin gene transfection on the extracellular signal-regulated protein kinase (ERK)siginal pathway. Methods Cultured mesangial cells were divided into seven groups:low glucose group (group A,5.5 mmol/L),high glucose group(group B,30 mmol/L),high glucose plus empty vector group (group C), high glucose plus megsin expression plasmid group (group D), high glucose plus megsin expression plasmids plus U0126 group (group E), high glucose plus megsin siRNA expression plasmids group (group F) and low glucose plus mannitol (24.5 mmol/L,group G). The expressions of megsin, PDGF-BB, pERK1/2, TGF-β1, as well as type Ⅳ collagen in GMCs of each group were detected by Western blotting, after being cultured for 12, 24 and 48 hours respectively. The concentration of type Ⅳ collagen in cell supernatant was measured by radioimmunochemistry. Results Compared with group A, the expression of megsin was increased in GMCs under high glucose medium, with an increase of PDGF-BB, pERK1/2, TGF-β1 in GMCs and type Ⅳ collagen in the supernatants (P＜0.05, respectively). The expression of above indices was in time-dependant manner. The over expression of megsin in exposure to high up-regulated the expression of PDGF-BB, pERK1/2, TGF-β1 and type Ⅳ collagen(P＜0.05, respectively). Compared with group D, the application of U0126 (pERK1/2 inhibitor) had no significant effect on the expression of megsin and PDGF-BB(P＞0.05, respectively). However, the expression of pERK 1/2,TGF-β1 and type Ⅳ collagen were obviously decreased (P＜0.05, respectively). Dowa-regulated expression of megsin by siRNA transfection decreased the expression of PDGF-BB, pERK1/2, TGFβ1 and type Ⅳ collagen(all P＜0.05). Conclusions The expression of megsin and PDGF-BB in GMCs with transfected megsin gene in high glucose medium is increased, possibly in a way of activating ERK signal pathway to some extent that boosts both the expression of TGF-β1 and the production of type Ⅳ collagen. The transfection of megsin siRNA inhibits the expression of obove indices, which probably contributes to the development of diabetic nephropathy.