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 investigate whether mild hypothermia can promote neurogenesis in the dentate gyrus of hippocampus and cognitive function recovery after traumatic brain injury ( TBI) through inhibiting apoptosis of hippocampal neurons. Methods A total of 66 healthy adult Sprague-Dawley rats were randomly divided into sham group, TBI group and TBI+hypothermia group, with 22 rats in each group. The rat TBI model was established using the fluid percussion device. The rats in TBI +hypothermia group received 4-hour hypothermia therapy immediately after injury, with the target temperature of 33. 5℃. Bromodeoxyuridine (BrdU) was injected into the rats' abdominal cavity to label the mitotic cells. The test of Morris water maze was used to evaluate the rats' spatial learning and memory capabilities. Immunofluorescence staining was used to observe the expression levels of BrdU, doublecortin (DCX), neuron specific nuclear protein (NeuN), cysteinyl aspartate specific proteinase 3 (caspase-3) and cleaved caspase-3 expressions in dentate gyrus of hippocampus at 7 days and 28 days after injury. Expressions apoptosis-related proteins including the factor associated suicide ( FAS )/factor associated suicide ligand (FASL), B-cell lymphoma-2 (Bcl-2), caspase-3 and cleaved caspase-3 expressions were detected by Western blot assay. Results The water maze tests at 28 days after injury showed that compared with TBI group, the escape latency in TBI+hypothermia group was significantly shorter [(24. 2 ± 5. 9)s:(18 ± 4. 1)s], and both the time in the target quadrant and the number of platform crossing were increasedsignificantly[(24.9±6.5)s:(31.7±5.2)s; (1.9±0.8) times:(3.5±1.2)times](P<0. 05). Compared with the sham group, in TBI group and TBI+hypothermia group, the BrdU+ new-born cells in the dentate gyrus of hippocampus were significantly increased at 7 days after injury [(9. 4 ± 4. 1):(33. 4 ± 3. 8);(9. 4 ± 4. 1):(45. 8 ± 5. 6)], the BrdU+ /DCX+ new-born neurons were increased at 7 days after injury [(2. 0 ± 0. 6):(9. 6 ± 1. 6);(2. 0 ± 0. 6):(19. 2 ± 3. 7)], and the BrdU+ /NeuN+mature neurons were increased at 28 days after injury [(2. 6 ± 1. 0) :(17. 2 ± 3. 9); (2. 6 ± 1. 0) :(33. 6 ± 9. 1)] (P<0. 01). TBI group showed more obvious increase than the TBI+hypothermia group (P<0. 01). Moreover, compared with 7 days after injury, the number of BrdU+ cells at 28 days after injury was further increased in TBI +hypothermia group but decreased in TBI group [(45. 8 ± 5. 6) :(58. 8 ± 9. 2);(33. 4 ± 3. 8):(22. 0 ± 3. 5)](P<0. 05 or <0. 01). Compared with the sham group, the caspase-3 +NeuN+ and caspase-3 +NeuN+ apoptotic neurons were significantly increased at 7 days after injury in TBI group [(2. 0 ± 0. 9):(11. 6 ± 2. 6); (2. 6 ± 1. 0):(10. 2 ± 2. 9)] (P<0. 05). Compared with the TBI group, the cleaved caspase-3 +NeuN+ apoptotic neurons were decreased in TBI+hypothermia group [(6. 6 ± 2. 0):(11. 6 ± 2. 6)](P<0. 05). Furthermore, compared with the TBI group, mild hypothermia might down-regulate the expression of FAS, FASL, cleaved caspase-3 and caspase-3 and up-regulate the expression of Bcl-2 in the hippocampus [(1. 54 ± 0. 15) :(1. 14 ± 0. 12);(1. 06 ± 0. 04):(0. 80 ± 0. 09); (0. 84 ± 0. 03):(0. 62 ± 0. 08); (0. 93 ± 0. 06):(0. 86 ± 0. 09);(0. 71 ± 0. 01):(1. 58 ± 0. 18)](P<0. 05). Conclusions Mild hypothermia might inhibit apoptosis of hippocampal neurons through cleaved caspase-3, FAS/FASL and Bcl-2 pathways, thus improving the neurogenesis and maturation of neurons in the dentate gyrus of hippocampus and facilitating cognitive function recovery in rats. It indicates that the function of hypothermia in anti-apoptosis and neurogenesis and maturity of hippocampal neurons may have a potential role in predicting the prognosis of TBI patients.

Objective To observe the expression of serine/threonine kinase 31 (STK31) in osteosarcoma and its effect on the malignant biological behavior of osteosarcoma.Methods Fifteen cases of osteosarcoma specimens and adjacent normal tissue were collected.The expression of STK31 in tumor tissues and normal tissue were detected by immunohistochemistry,real-time quantitative PCR and Western blot.The STK31 knockout plasmids PGenesil-STK31-shRNA or control plasmid pGenesil-1 were transfected into osteosarcoma cell line MG63 cells.The effect of STK31 on the proliferation of MG63 cells was detected by CCK8 cell activity assay.Tanswell experiment was used to observed the effect of STK31 on the migration ability of osteosarcoma cells.Results Immunohistochemical showed that STK31 expressed in the tumor tissue,and it was significantly higher than the adjacent normal tissues;Real time quantitative PCR[(3.65±0.83)vs.(1.05±0.14),P＜0.05] and Western blot also revealed that STK31 expression in tumor tissue were significantly higher than adjacent normal tissues(P＜0.05);CCK8 experiments showed that knockdown STK31 inhibited proliferation of MG63 cell when compared with the control group after 36 h[(1.71±0.17)vs.(1.39±0.11),P＜0.05],72 h[(2.15±0.21)vs.(1.54±0.14),P＜0.05];Tansewell experiments showed that transfection of pGenesil-STK31-shRNA could suppress MG63 cell's migration[(13±4)vs.(55±8),P＜0.05].Conclusion STK31 is overexpression in osteosarcoma with increased biological activity of osteosarcoma cells.

Objective To study the effect of γ-rays irradiation on the differentiation potential of the human peripheral blood monocytes (PBMCs) into osteoclast-like cells (OCLs) in vitro.Methods PBMCs were isolated by density gradient centrifugation,treated by receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) and exposed to 137Cs γ-rays with different radiation doses (0,0.75,2 Gy).After seven days of incubation,the cells were stained for tartrate resistant acid phosphatase (TRAP) and bone slices were stained by toluidine blue on the tenth day.Meanwhile,the characteristic osteoclast markers including Cathepsin K and integrin β3 were analyzed by real-time PCR.Tartrate resistant acid phosphatase 5b (TRAcP-5b) in the culture supernatant wasdetermined by ELISA.Results PBMCs were differentiated into OCLs by the treatments of RANKL and MCSF.The number of TRAP positive multinucleated OCLs was significantly higher in the dose of 0.75 Gy group than in control (0 Gy) group (t =3.451,P ＜ 0.05).Compared with the control group,the expression levels of Cathepsin K and integrin β3 and the concentration of TRAcP-5b were significantly elevated (t =2.343,2.728,3.631,P ＜ 0.05).However,in the 2 Gy group,there was a decrease in the number of osteoclasts,mRNA expression level of osteoclast characteristic markers and TRAcP-Sb,but no statistically significant differences compared with the control group.Conclusions Ionizing radiation may influence the osteoclastogenesis during the PBMCs differentiation to OCLs.At low dosage,ionizing radiation promotes osteoclastogenesis and enhances the resorptive activity of osteoclasts,but a decline of differentiation potential was observed at high dosage of radiation.

Objective To explore the feasibility of using glycophorin A somatic mutation in peripheral erythrocytes,in order to evaluate the cancer risk of occupational medical exposure to ionizing radiation.Methods Totally 336 medical radiation workers were recruited as three groups (general radiation group,computer tomography group,intervention and radiation treatment group) and 112 healthy adults were selected as control by using stratified random cluster sampling method,where 176 medicalradiation workers and 58 health controls had a MN-heterozygous type.The erythrocytes were fixed and bound with fluorescent-labeled monoclonal antibody,and the glycophorin A somatic mutation frequency was assayed by a modified BR6-1W1 method using a FACScan flow cytometer.The individual susceptibility to radiation was investigated using micronuclei test and 3-Aminobenzamide index test.Results The GPA somatic mutation frequency of medical-radiation workers was significantly higher than that of healthy control ( t =2.29 - 11.48,P ＜ 0.05 ).In particular,the NO GPA aberration frequency of interventional radiology workers was much higher than that of the general medical diagnostic workers (t =2.01,P ＜ 0.05).In addition,the NO GPA variant frequency changed significantly with the years of radiation service,cumulative doses,and 3AB index.However,the NN GPA variant frequency was only associated with the years of radiation service,and no significant correlations were found between NN GPA variant frequency and cumulative dose of radiation exposure or 3AB index. Conclusions GPA mutation frequency,especially NO GPA mutation frequency could be used as a sensitive biomarker to predict the DNA damage and individual susceptibility for the population exposed to professional low-dose ionizing radiation.