1.Relationship between serum klotho level and risk of all-cause mortality in the population with diabetic kidney disease
Jing WANG ; Jingjing JIN ; Jia LIU ; Lifang HE ; Yanyun XUE
Chinese Journal of Nephrology 2025;41(10):731-737
Objective:To investigate the association between serum klotho level and risk of all-cause mortality in the population with diabetic kidney disease (DKD).Methods:It was a retrospective cohort study. DKD patients from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which covered five survey cycles from 2007 to 2016 were selected. Relevant demographic and laboratory examination data were collected, and all-cause mortality was regarded as the endpoint event. Patients were divided into high serum klotho group and low serum klotho group according to the optimal klotho threshold of predicting survival outcomes, and the differences of baseline characteristics between the two groups were compared. The weighted Kaplan-Meier method was used to draw the survival curves of the high and low serum klotho groups during the follow-up period. Log-rank test was used to compare the survival rates between the two groups. Weighted Cox proportional hazards regression analysis and further stratified analysis were used to estimate the correlation between serum klotho level and the risk of all-cause mortality.Results:A total of 633 DKD patients were included in this study, with age of 65 (56, 72) years, and 323 (51.03%) males. Among them, there were 510 patients in the high klotho level (>556.6 ng/L) group, and 123 patients in the low klotho level (≤556.6 ng/L) group. The serum creatinine level in the high klotho level group was significantly lower than that in the low klotho level group ( Z=-2.650, P=0.010), while the estimated glomerular filtration rate (eGFR, Z=2.489, P=0.015) and fasting blood glucose ( Z=2.275, P=0.026) were significantly higher than those in the low klotho level group. There was no statistically significant difference between the two groups in terms of age, gender distribution, racial distribution, proportion of smoking, body mass index, proportion of hypertension, total cholesterol, triglyceride, and urine albumin/creatinine ratio (all P>0.05). The follow-up time was 81 (49, 116) months, and a total of 204 (32.23%) all-cause death events occurred. Kaplan-Meier survival analysis showed that the survival rate of the high klotho level group was significantly higher than that of the low klotho level group (Log-rank test, χ2=4.21, P=0.040). Cox proportional hazards regression analysis showed that, after adjusting for gender, age, race, smoking, body mass index, hypertension, blood glucose, triglyceride, total cholesterol and eGFR, the risk of all-cause death in the low klotho level group was 1.63 times than that in the high klotho level group ( HR=1.63, 95% CI 1.03-2.63). Further stratified analysis showed that there was no interaction effect of age, gender, race and eGFR on the impact between low serum klotho level and the risk of all-cause death (all P>0.05), indicating that the correlation between low serum klotho level and the risk of all-cause death was consistent when DKD individuals were divided into different subgroups. Conclusions:Low serum klotho level are significantly associated with increased risk of all-cause mortality in the DKD population. Maintaining an adequate serum klotho level may reduce the risk of death in DKD patients.
2.Relationship between serum klotho level and risk of all-cause mortality in the population with diabetic kidney disease
Jing WANG ; Jingjing JIN ; Jia LIU ; Lifang HE ; Yanyun XUE
Chinese Journal of Nephrology 2025;41(10):731-737
Objective:To investigate the association between serum klotho level and risk of all-cause mortality in the population with diabetic kidney disease (DKD).Methods:It was a retrospective cohort study. DKD patients from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which covered five survey cycles from 2007 to 2016 were selected. Relevant demographic and laboratory examination data were collected, and all-cause mortality was regarded as the endpoint event. Patients were divided into high serum klotho group and low serum klotho group according to the optimal klotho threshold of predicting survival outcomes, and the differences of baseline characteristics between the two groups were compared. The weighted Kaplan-Meier method was used to draw the survival curves of the high and low serum klotho groups during the follow-up period. Log-rank test was used to compare the survival rates between the two groups. Weighted Cox proportional hazards regression analysis and further stratified analysis were used to estimate the correlation between serum klotho level and the risk of all-cause mortality.Results:A total of 633 DKD patients were included in this study, with age of 65 (56, 72) years, and 323 (51.03%) males. Among them, there were 510 patients in the high klotho level (>556.6 ng/L) group, and 123 patients in the low klotho level (≤556.6 ng/L) group. The serum creatinine level in the high klotho level group was significantly lower than that in the low klotho level group ( Z=-2.650, P=0.010), while the estimated glomerular filtration rate (eGFR, Z=2.489, P=0.015) and fasting blood glucose ( Z=2.275, P=0.026) were significantly higher than those in the low klotho level group. There was no statistically significant difference between the two groups in terms of age, gender distribution, racial distribution, proportion of smoking, body mass index, proportion of hypertension, total cholesterol, triglyceride, and urine albumin/creatinine ratio (all P>0.05). The follow-up time was 81 (49, 116) months, and a total of 204 (32.23%) all-cause death events occurred. Kaplan-Meier survival analysis showed that the survival rate of the high klotho level group was significantly higher than that of the low klotho level group (Log-rank test, χ2=4.21, P=0.040). Cox proportional hazards regression analysis showed that, after adjusting for gender, age, race, smoking, body mass index, hypertension, blood glucose, triglyceride, total cholesterol and eGFR, the risk of all-cause death in the low klotho level group was 1.63 times than that in the high klotho level group ( HR=1.63, 95% CI 1.03-2.63). Further stratified analysis showed that there was no interaction effect of age, gender, race and eGFR on the impact between low serum klotho level and the risk of all-cause death (all P>0.05), indicating that the correlation between low serum klotho level and the risk of all-cause death was consistent when DKD individuals were divided into different subgroups. Conclusions:Low serum klotho level are significantly associated with increased risk of all-cause mortality in the DKD population. Maintaining an adequate serum klotho level may reduce the risk of death in DKD patients.
3.Establishment of fingerprints and differential component identification of cultivated and wild Anemarrhena asphodeloides
Xinxin CHANG ; Qian LI ; Zijing XUE ; Songsong JING ; Yanyun ZHAO ; Yuguang ZHENG ; Junna SONG
China Pharmacy 2022;33(2):146-152
OBJECTIVE To establish the fingerprints of c ultivated and wild Anemarrhena asphodeloides,and to identify their differential components. METHODS Using an evaporative light-scattering detector , the high performance liquid chromatography combined with Similarity Evaluation System of TCM Chromatographic Fingerprint (2012 edition) were used to establish fingerprints of 14 batches of cultivated A. asphodeloides and 14 batches of wild medicinal materials ,and evaluate their similarity. The common peaks were identified by comparison with the chromatogram of the mixed control. At the same time ,the contents of components corresponding to common peaks in cultivated and wild A. asphodeloides were determined. The principal component analysis and orthogonal partial least squares discrimination analysis were adopted to identify differential components of them ,and compare the contents of them. RESULTS Among 28 batches of A. asphodeloides ,10 common peaks were found ,i.e. neomangiferin(peak 1),mangiferin(peak 2),isomangiferin(peak 3),timosaponin B Ⅱ(peak 7),timosaponin B Ⅲ(peak 8), timosaponin Ⅰ(peak 9),timosaponin A Ⅲ(peak 10). The similarities of fingerprints of samples with control fingerprint were no less than 0.963. The average total contents of seven components in cultivated and wild A. asphodeloides were 74.18 and 84.72 mg/g, respectively;there was statistical significance (P<0.05). The cultivated and wild A. asphodeloides could be divided into two categories. The differential components were neomangiferin ,mangiferin,timosaponin B Ⅱ and timosaponin A Ⅲ(VIP values were all higher than 1). The content of neomangiferin in cultivated products was significantly higher than that in wild products (P< 0.05),and the contents of mangiferin ,timosaponin B Ⅱ and ti mosaponin A Ⅲ were significantly lower than those in wild products (P<0.05). CONCLUSIONS Fingerprint of A. asphodeloides is established ,and differential components of cultivated and wild A. asphodeloides are identified primarily.
4.Expression characteristics and significance of miR-338-5p in renal transplant pa-tients
Xuyi MA ; Haiyan XU ; Xiaozhou HE ; Panpan DONG ; Dong XUE ; Yanyun ZHANG ; Xueguang ZHANG
Chinese Journal of Immunology 2014;(8):1108-1113
To explore the serum miR-338-5p expression characteristics in renal transplant recipients ,and the role of regulating BAFF signal ,then investigate its biological significance.Methods:Healthy volunteers were enrolled as control group.Serum miR-338-5p was detected by real-time PCR;soluble BAFF was detected by ELISA;anti-HLA-Ⅰantibody,anti-HLA-Ⅱ antibody and anti-MICA antibody were detected by liquid chip technology.SPSS17.0 software was applied.t-test was used to compare the means of two independent samples;Paired samples t-test was used to compare the means of two paired samples;Spearman method and Pearson method were used to analyse the correlation;P<0.05 was considered to be statistically significant.Results: Compared with healthy controls,serum miR-338-5p in renal transplant recipients decreased significantly (P<0.001),while serum BAFF increased significantly (P<0.01).Serum miR-338-5p levels within 1 year post-transplantation were significantly lower than that of more than 1 year post-transplantation (P<0.01);Serum miR-338-5p levels within 3 years post-transplantation were significantly lower than that of more than 3 years post-transplantation (P<0.01);To all research objects,serum miR-338-5p was significantly negatively correlated with serum BAFF (r=-0.51,P<0.001),and serum miR-338-5p was significantly negatively correlated with anti-HLA-Ⅱ antibody(r=-0.322, P<0.05);Serum miR-338-5p within 3 years was significantly negatively correlated with anti-HLA-Ⅱantibody (r=-0.423,P<0.05), and serum miR-338-5p within 3 years was significantly negatively correlated with anti-MICA antibody(r=-0.411,P<0.05);Serum miR-338-5p more than 3 years was significantly positively correlated with anti-MICA antibody(r=0.486,P<0.05),and Serum miR-338-5p more than 3 years was significantly positively correlated with anti-HLA & MICA antibody(r=0.578,P<0.01).Conclusion:miR-338-5p may directly or indirectly target BAFF signal ,and participate antibody mediated immune response by regulating its target genes and interfere with the long-term survival of transplanted renal.
5.Involvement of miR-338-5p in antibody-mediated renal allograft rejection by targeting TRAF3
Haiyan XU ; Xiaozhou HE ; Xuyi MA ; Dong XUE ; Yanyun ZHANG ; Xueguang ZHANG
Chinese Journal of Organ Transplantation 2013;34(9):554-558
Objective To explore the significantly differentially.expressed microRNAs during antibody-mediated renal allograft rejection.Method MicroRNA array assay was used,and the obtained data were analyzed by bioinformatics analysis.The obtained significant microRNAs were further analyzed to forecast the targeted genes in the common database,then experimental means were used to testify the targeted genes.Result During the antibody-mediated renal allograft rejection,the significantly over-expressed microRNAs were miR-200c,miR-200b,miR-30c,miR-30b and miR-30e+,etc.The significantly down-expressed microRNA was miR-338-5p.The bioinformatics analysis results indicated that TRAF3 was the targeted gene of miR-338-5p,which was testified by real time PCR,immunohistochemical assay and fluorescence reporter assay.Conclusion miR-338-5p anticipated in the antibody-mediated renal allograft rejection by targeting TRAF3.
6.Effects of fluoxetine on special learning and memory and serum S100B level in depressed model rats
Xue YU ; Kun YANG ; Hao LIU ; Xiaozheng LING ; Yanyun LI
Chinese Journal of Behavioral Medicine and Brain Science 2012;21(5):389-391
ObjectiveTo explore the effects of fluoxetine on special learning and memory and serum S100B level in depressed model rats.MethodsAdult male SD rats were divided into six groups randomly according random digits table:control group ( A ),depressed model group ( B ),group of depressed model treated with single dose of fluoxetine for one day ( C ),group of depressed model treated with fluoxetine for one week (D),group of depressed model treated with fluoxetine for two weeks (E) and group of depressed model treated with fluoxetine for four weeks (F),ten rats in each group.Except control group,others were subjected to forced-swimming for four weeks,15 min a day.Fluoxetine (10 mg/kg) was given intragastric administration to group C-F before swimming everyday.Morris water maze ( MWM ) was used to measure the spatial learning and memory of rats.ELISA was used to determine the level of serum S100B.ResultsIn the hiding platform test of MWM,there was significant longer of escape latency (EL) in B group than that in A group(P < 0.05 ).And the EL in all groups treated with fluoxetine became shorter with the prolonging of treatment.In the probe test,there were significant longer time in target quadrant in D,E,F than in other quadrant (F =5.162,P < 0.01 ).The levels of serum S100B were lower in E,F groups ( E group ( 0.91 ± 0.23 ) ng/ml,F group ( 0.85 ± 0.21 ) ng/ml) than that in B group (( 1.26 ±0.61 )ng/ml,P<0.05).ConclusionChronic administration of fluoxetine could improve the impairment of spatial learning and memory and reverse the increase of S100B level in serum of depressed model rats.

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