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 This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

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 This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:To investigate the current situation of occurrence of social isolation in maintenance hemodialysis patients and analyze its influencing factors, in order to provide a theoretical basis for the implementation of targeted interventions.Methods:The study was a cross-sectional study. A total of 315 dialysis patients in three hemodialysis centers in Xinjiang were selected by simple sampling method from October 2021 to March 2022, who were investigated using the general information questionnaire, Lubben-6 social network scale, International Physical Activity Questionnaire (sedentary behavior section), Patient Health Questionnaire 9-item scale (PHQ-9) and Frail Scale. Univariate analysis and binary Logistic regression analysis were used to explore the influencing factors affecting the social isolation of dialysis patients.Results:Social isolation was present in 28.89% (91/315) of maintenance hemodialysis patients, and binary Logistic regression analysis revealed that age (45-59 years old: OR=4.815, 95% CI 1.362-17.017;≥60 years old: OR=8.968, 95% CI 2.349-34.236), dialysis age ( OR=2.788, 95% CI 1.334-5.826), sedentary behavior ( OR=2.504, 95% CI 1.406-4.461), depression ( OR=2.095, 95% CI 1.179-3.722), and debilitation ( OR=2.043, 95% CI=1.062-3.933) were influencing factors of social isolation in maintenance hemodialysis patients (all P<0.05). Conclusions:The occurrence of social isolation in maintenance hemodialysis patients was closely associated with advanced age, high dialysis age, sedentary behavior, debilitation, and depressive status, suggesting that medical staff in hemodialysis centers can implement targeted interventions to prevent or improve the level of social isolation in patients based on relevant influencing factors.

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

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.

Gut microbiota are closely related to human health. Studies have shown that probiotics, prebiotics and synbiotics play an important role in maintaining intestinal microbiota balance and improving blood glucose, but their use is limited in certain special periods, such as pregnancy, immunodeficiency, and severe infection. Postbiotics is defined as inactivated bacteria and bacterial components that are beneficial for the host, including cell structure, secretory molecules or metabolites and inanimate microorganisms. The heterogeneous molecular metabolite shows a wide range of action mechanisms and plays an important role in restoring intestinal flora and improving blood glucose. This paper reviews the mechanism and research progress of postbiotics regulation of blood glucose.

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 explore the clinical features, diagnosis, and treatment of congenital disorder of glycosylation type 1a (CDG-Ⅰa), a rare inherited metabolic disease. Methods The clinical data and the gene detection results of one case of CDG-Ia which was discovered because the case had encephalopathy and hepatopathy were retrospectively analyzed. The related literatures were reviewed. Results Male infant suffered with face and trunk rash, motor development retardation, malnutrition, cheek fat plump, low limbs muscle tone, and bilateral crater nipple at 3 months old. Abnormal liver function and mild renal impairment were found after examination. The development quotient was low. Head MRI showed that bilateral frontal and temporal sulcus widening, and cerebellar atrophy. Urinary organic acids, amino acids, carnitine, and biotin activities were normal. Gene sequencing revealed that there were two heterozygous mutations, c.430T>C (p.F144L) and c.713G>C (p.R238P), in the PMM2 gene. The diagnosis of CDG-Ⅰa was confirmed. Both of the infant's parents were healthy, and each of them carries a pathogenic mutation. The infant had an elder brother who had mental disorder and died for liver and kidney function damage and hydronephrosis at 8 months old. Conclusion CDG-Ⅰa is an autosomal recessive disease. For infants with unexplained multiple organ damage, especially combined with intelligent and motor development retardations, strabismus, nipple retraction, and cerebellar atrophy, the possibility of CDG-Ⅰa should be considered. Gene detection of PMM2 can help the diagnosis.