BACKGROUND:Plasma coagulation factors have been shown to be strongly associated with chronic kidney disease in many observational studies.Nevertheless,the causal relationship between plasma coagulation factors and chronic kidney disease has not been fully revealed.OBJECTIVE:To assess and explore the association between plasma coagulation factors and chronic kidney disease risk using a two-sample Mendelian randomization approach.METHODS:Genome-wide association study data of 39 plasma coagulation factors with different ID numbers were obtained from the GWAS Catalog database and chronic kidney disease genome-wide association analysis data(ebi-a-GCST003374)were obtained from the Open Genome-Wide Association Study database(IEU Open GWAS),where the sample size of the chronic kidney disease dataset was 117 165 cases and the number of single nucleotide polymorphisms was 2 179 497.Inverse variance weighting,MR-Egger regression,weighted median,weighted mode,and simple mode were used to explore causality.Meanwhile,Cochran Q test was used to assess the variability of single nucleotide polymorphism loci.Horizontal pleiotropy of single nucleotide polymorphisms was verified by MR-Egger intercept test.Sensitivity analyses were performed using the"leave-one-out"method to determine whether the Mendelian randomization results would be confounded by a single single nucleotide polymorphism site.RESULTS AND CONCLUSION:(1)A total of four plasma coagulation factors were associated with chronic kidney disease by Mendelian randomization analysis of 39 plasma coagulation factors and chronic kidney disease.Plasma coagulation factor V(FV)level(odds ratio[OR]=0.922,95％confidence interval[CI]:0.875-0.971,P=0.002),plasma FVII level(OR=0.719,95％CI:0.521-0.991,P=0.044),plasma FXa level(OR=1.113,95％CI:1.009-1.227,P=0.032),plasma antithrombin-level(OR=0.849,95％CI:0.739-0.975,P=0.020)were significantly associated with chronic kidney disease(all P＜0.05).Horizontal pleiotropy and heterogeneity were not detected.(2)Based on the two-sample Mendelian randomization in the genetic epidemiologic method,plasma FVII level,plasma antithrombin-level,and plasma FV level of coagulation factors were protective factors for the risk of chronic kidney disease,and plasma FXa level was a risk factor of chronic kidney disease.(3)The above results confirm that there is a significant potential causal relationship between plasma coagulation factors and chronic kidney disease.Although we analyzed the data of European populations from international databases,these data analyses have a reference value for the study of chronic kidney disease and coagulation factors in China,and they also provide innovative insights into the study of the genetic epidemiology of chronic kidney disease,and they also provide a certain reference value for the in-depth study of the related databases in China,including the China Health and Retirement Longitudinal Study database.Future studies can focus on the assessment of hypocoagulability or hypercoagulability of related coagulation factors in patients with chronic kidney disease.

BACKGROUND:Plasma coagulation factors have been shown to be strongly associated with chronic kidney disease in many observational studies.Nevertheless,the causal relationship between plasma coagulation factors and chronic kidney disease has not been fully revealed.OBJECTIVE:To assess and explore the association between plasma coagulation factors and chronic kidney disease risk using a two-sample Mendelian randomization approach.METHODS:Genome-wide association study data of 39 plasma coagulation factors with different ID numbers were obtained from the GWAS Catalog database and chronic kidney disease genome-wide association analysis data(ebi-a-GCST003374)were obtained from the Open Genome-Wide Association Study database(IEU Open GWAS),where the sample size of the chronic kidney disease dataset was 117 165 cases and the number of single nucleotide polymorphisms was 2 179 497.Inverse variance weighting,MR-Egger regression,weighted median,weighted mode,and simple mode were used to explore causality.Meanwhile,Cochran Q test was used to assess the variability of single nucleotide polymorphism loci.Horizontal pleiotropy of single nucleotide polymorphisms was verified by MR-Egger intercept test.Sensitivity analyses were performed using the"leave-one-out"method to determine whether the Mendelian randomization results would be confounded by a single single nucleotide polymorphism site.RESULTS AND CONCLUSION:(1)A total of four plasma coagulation factors were associated with chronic kidney disease by Mendelian randomization analysis of 39 plasma coagulation factors and chronic kidney disease.Plasma coagulation factor V(FV)level(odds ratio[OR]=0.922,95％confidence interval[CI]:0.875-0.971,P=0.002),plasma FVII level(OR=0.719,95％CI:0.521-0.991,P=0.044),plasma FXa level(OR=1.113,95％CI:1.009-1.227,P=0.032),plasma antithrombin-level(OR=0.849,95％CI:0.739-0.975,P=0.020)were significantly associated with chronic kidney disease(all P＜0.05).Horizontal pleiotropy and heterogeneity were not detected.(2)Based on the two-sample Mendelian randomization in the genetic epidemiologic method,plasma FVII level,plasma antithrombin-level,and plasma FV level of coagulation factors were protective factors for the risk of chronic kidney disease,and plasma FXa level was a risk factor of chronic kidney disease.(3)The above results confirm that there is a significant potential causal relationship between plasma coagulation factors and chronic kidney disease.Although we analyzed the data of European populations from international databases,these data analyses have a reference value for the study of chronic kidney disease and coagulation factors in China,and they also provide innovative insights into the study of the genetic epidemiology of chronic kidney disease,and they also provide a certain reference value for the in-depth study of the related databases in China,including the China Health and Retirement Longitudinal Study database.Future studies can focus on the assessment of hypocoagulability or hypercoagulability of related coagulation factors in patients with chronic kidney disease.

Objective To observe the changes of liver function,blood cell,and lung function of healthy young and middle-aged men before and after fast-advancing short-term high altitude exposure(FSHAE);and to explore the effects and possible mechanisms of FSHAE on the function of liver,blood cells,and lung tissues.Methods This study included 48 healthy young and middle-aged male volunteers,who collected physiological indicators,tested liver function indicators,blood cell indicators,and lung function-related indicators 1 day before entering the plateau(100m above sea level),and 15 days after FSHAE(3000m above sea level).Differences in the relevant parameters of each system were compared before and after FSHAE.Results Compared with those before entering the plateau,the physiological parameters of young and middle-aged men after 15 days of FSHAE heart rate increased significantly,respiratory rate increased,systolic blood pressure increased,mean arterial blood pressure increased,oxygen saturation decreased(P＜0.01),and diastolic blood pressure increased(P＜0.05),all of which were statistically significant;and the indicators of liver function:glutamic oxaloacetic aminotransferase,glutamic alanine aminotransferase increased(P＜0.01),glutamylamine aminotransferase,glutamate aminotransferase,glutaminase,and pulmonary function were increased(P＜0.01),glutamyl transpeptidase,alkaline phosphatase,and total bile acids were elevated,and total protein decreased(P＜0.05),and the differences were statistically significant.Hemocyte-related indexes:erythrocyte count,erythrocyte pressure volume,mean erythrocyte volume,mean hemoglobin volume,mean hemoglobin concentration,and hemoglobin were elevated,and platelet count decreased(P＜0.01),and the differences were statistically significant.although there was an elevation of leukocyte count(P＞0.05);Lung function-related indexes:decreased exertion lung volume(P＜0.05).There were decreased exertion expiratory volume in the first second,increased one-second rate(P＞0.05).Conclusion FSHAE can lead to oxidative stress in the organism,and acute hypoxic multisystemic injury will occur,with the simultaneous emergence of hypoxic adaptive regulation of various systems,self-compensatory repair of various organs of the organism,and there may be the possibility of interactions between various systems.

Objective:To investigate the effects of rapid short-term altitude exposure on thyroid related hormone parameters in healthy male pilots.Methods:A total of 132 healthy male pilots who lived in the plain were selected by random number table method to enter the plateau, with an average altitude of 3 000 m, within 3 h by plane from the plain, with an average altitude of 100 m, from March 2023 to April 2023, and returned to the plain within 3 h by plane 15 d later. General physiological indices, thyroid related hormone parameters [thyroid stimulating hormone (TSH), total thyroid hormone (TT 4), free thyroxine (FT 4), free triiodothyronine (FT 3), total triiodothyronine (TT 3), thyroglobulin antibody (TgAb), anti-thyroid peroxidase antibody (TPOAb), and thyroglobulin (Tg)] were collected from the pilots 1 day before the rush into plateau exposure and after 15-day plateau exposure. The differences in thyroid related hormone parameters of the pilots before and after acute short-term plateau exposure were compared. Results:As compared with the parameters before entering the plateau, the heart rate, respiratory rate, systolic and diastolic blood pressure of pilots were increased and oxygen saturation was decreased after 15 d plateau exposure, and the differences were statistically significant ( t=8.65, 10.78, 13.39, 12.49, 17.72, all P<0.001). The levels of TSH, FT 4, TPOAb and Tg of pilots were all decreased after 15 d plateau exposure, and the differences were significant ( t=3.67, 2.17, Z=-4.63, -7.49, P=0.003, 0.049, <0.001, <0.001). The levels of TT 4 and TT 3 were elevated, with significant differences ( t=4.08, 2.55, P<0.001, =0.024). TgAb level was less discrete, but the difference was significant ( Z=-2.36, P=0.018). Conclusions:By rush into plateau and short-term exposure, the healthy male pilots showed decreased TSH, FT 4, TPOAb and Tg, and increased TT 4 and TT 3, and those may result in the thyroid gland due to acute stress and low-pressure hypoxia appeared related to the hormone metabolism and protein changes.

Objective:To investigate the effects of rapid short-term altitude exposure on thyroid related hormone parameters in healthy male pilots.Methods:A total of 132 healthy male pilots who lived in the plain were selected by random number table method to enter the plateau, with an average altitude of 3 000 m, within 3 h by plane from the plain, with an average altitude of 100 m, from March 2023 to April 2023, and returned to the plain within 3 h by plane 15 d later. General physiological indices, thyroid related hormone parameters [thyroid stimulating hormone (TSH), total thyroid hormone (TT 4), free thyroxine (FT 4), free triiodothyronine (FT 3), total triiodothyronine (TT 3), thyroglobulin antibody (TgAb), anti-thyroid peroxidase antibody (TPOAb), and thyroglobulin (Tg)] were collected from the pilots 1 day before the rush into plateau exposure and after 15-day plateau exposure. The differences in thyroid related hormone parameters of the pilots before and after acute short-term plateau exposure were compared. Results:As compared with the parameters before entering the plateau, the heart rate, respiratory rate, systolic and diastolic blood pressure of pilots were increased and oxygen saturation was decreased after 15 d plateau exposure, and the differences were statistically significant ( t=8.65, 10.78, 13.39, 12.49, 17.72, all P<0.001). The levels of TSH, FT 4, TPOAb and Tg of pilots were all decreased after 15 d plateau exposure, and the differences were significant ( t=3.67, 2.17, Z=-4.63, -7.49, P=0.003, 0.049, <0.001, <0.001). The levels of TT 4 and TT 3 were elevated, with significant differences ( t=4.08, 2.55, P<0.001, =0.024). TgAb level was less discrete, but the difference was significant ( Z=-2.36, P=0.018). Conclusions:By rush into plateau and short-term exposure, the healthy male pilots showed decreased TSH, FT 4, TPOAb and Tg, and increased TT 4 and TT 3, and those may result in the thyroid gland due to acute stress and low-pressure hypoxia appeared related to the hormone metabolism and protein changes.

Objective:To construct the plant expression vector of Der f1 allergen of Dermatophagoides pteronyssinu and expression in tobacco lamina.Methods:The Der f1 gene was amplified from the glycerin bacterium which contained pET28a(+)-Der f1 plasmid,cloned into the pMD 19-T plasmid,and then sequenced.The Der f1 gene was digested by ClaⅠand SalⅠ,and cloned into potato virus X (PVX) to construct plant expression vector PVX-Der f1,and then was transformed agrobacterium tumefaciens.The positive one was selected to infect tobacco lamina for expressing target protein.The protein was identified and analysed by SDS-PAGEand Western blot.Results:Digestion and sequence analysis confirmed that the plant expression vector was correct,and the SDS-PAGE and Western blot results showed that the molecular weight of the protein was about 34M_r and it could specific binding with positive serum.Conclusion:The plant expression vector of Der f1 is successfully constructed and the recombinant protein is also produced.

Objective To obtain the gene coding for the group 5 allergens from Dermatophagoides farinae ( Derf5 ) and predict its molecular characteristics. Methods The total RNA of D. farinae were extracted, and the gene Derf5 was amplified by RT-PCR with the primers designed according to previous sequence published in GenBank. The target gene was linked into pMD19-T Simple plasmid, sequenced and analyzed by bioinformatics software. Results The sequence homology reached to 97.8% between our sequenced result with one complete open reading fragment (ORF) and the reference. The gene encode an extracellular hydrophobic protein with 132 amino acid resides, one signal peptide from 1 to 19 position and one transmembrane domain from 1 to 19 position. The secondary structure was composed of extended strand (1. 52% ), random coil (7.58%) and alpha helix (90.91%). The encoded protein was deduced to have two Casein kinase Ⅱ phosphorylation sites. The similarity of the amino acid sequence of the group 5 allergens were 78% between D. farinae and D. pteronyssinus. Conclusion The gene Derf5 was cloned successfully, and its characteristics was primarily predicted.