OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective To investigate the effect of different radiation doses on the accuracy of iodine quantification and CT value of virtual monochromatic image with a muti-spectral CT iodine phantom using second-generation dual-layer detector spectral CT(DLCT).Methods The second-generation DLCT scan abdominal phantom was used,which consisted of six different concentrations of iodine rods at 4,8 and 12 g/L.The scan parameters were set at 100,120 and 140 kVp tube voltages,and six radiation exposure sequences were scanned at each tube voltage:5,10,15,20,25 and 30 mGy.Measure the iodine concentration value and the CT value at the single level of 50,70 and 100 keV,and calculate the absolute error value of iodine concentration and CT value under different radiation exposure.SPSS 22.0 software single factor analysis of variance was used to compare the difference between the io-dine concentration and the absolute error of CT value under different Radiation exposure,and LSD method was used to compare the two groups.Results The absolute error of CT value of 4 g/L iodine rod with 10～30 mGy scanning at 100 keV energy level was significantly higher than that of 12 g/L and 8 g/L(P＜0.05),and the absolute error of iodine concentration measurement of other iodine rods with different concentrations at different Radiation exposure had no statistical difference.Conclusions The second-generation double-layer detector spectral CT has high meas-urement stability for iodine concentration quantification and CT value accuracy under conditions of radiation dose greater than 5 mGy.

Objective : To explore the effects of an ultradian light cycle on the periodic expression of glutamate re⁃ ceptors in the suprachiasmatic nucleus and the lateral habenula nucleus. Methods : An ultradian light cycle T7 (3. 5 hours/3. 5 hours light : dark) was used to establish an ultradian light cycle model group and T24( 12 hours/ 12 hours light : dark) was used to establish control group. The expression of key proteins in the brain regions of the suprachiasmatic nucleus ( SCN) and the lateral habenula ( LHB) of the hypothalamus were analyzed by Western blot. Including glutaminergic receptors , pituitary adenylate cyclase activating polypeptide (PACAP) receptors , and downstream signaling molecules. Results : Western blot results showed that the expression of α⁃amino⁃3 ⁃hydroxy⁃5 ⁃methyl⁃4 ⁃isoxazole⁃propionic acid receptor subunit 2 (GluR2) in SCN under Zeitgeber time (ZT ) 1 and ZT 5 increased under an ultradian light cycle compared with normal photoperiod ( P < 0. 05 , P < 0. 01) , the overall expression of GluR2 in T7 group was higher than that in T24 group (P < 0. 01) , the overall expression of GluR2 in LHB group T7 was lower than that in T24 group (P < 0. 01) . Compared with T24 photoperiod , the overall expression of N ⁃methyl⁃D ⁃aspartic acid receptor subunit 2 (NR2B) in SCN increased under T7 photoperiod (P < 0. 05) , the overall expression of phosphorylation of extracellular signal⁃related kinase ( P⁃ERK) in LHB significantly increased under T7 photoperiod (P < 0. 05) . Conclusion An ultradian light cycle would cause an up⁃regulating of GluR2 and NR2B expression , a down⁃regulating of GluR2 expression and up⁃regulating P ⁃ERK expression in LHB.

Objective:To explore application value of improving quality of the low dose pancreatic CT images by using deep learning reconstruction (DLR).Methods:From August to December 2020, 68 patients who underwent contrast-enhanced pancreatic CT were prospectively collected in Peking Union Medical College Hospital. All patients were randomly divided into routine dose group (34 patients, with tube voltage of 120 kV) and low dose group (34 patients, with tube voltage of 100 kV). All patients underwent non-contrast, arterial phase, parenchymal phase and delay phase scans. The four-phase images of low dose group were reconstructed by using filtered back projection (FBP), hybrid iterative reconstruction (AIDR) and DLR which were marked with LD-FBP, LD-AIDR and LD-DLR, respectively. The four-phase images of routine dose group were reconstructed by using AIDR algorithm which were marked with RD-AIDR. The CT value, image noise (SD), signal to noise ratio (SNR) and contrast to noise ratio (CNR) of pancreas were measured. The ANOVA test was performed in comparison with objective parameters of different reconstruction algorithms, and LSD test was performed in pairwise comparison. The subjective image scores were obtained and were compared using Kruskal-Wallis test.Results:CT value, SD, SNR and CNR of non-contrast, arterial phase, parenchymal phase and delay phase had significant difference among different reconstruction images of routine dose group and low dose group (all P<0.05). The CT value of LD-FBP, LD-AIDR, and LD-DLR images were significantly higher than those of RD-AIDR images in parenchymal phase and delay phase (all P<0.05). There were statistically significant differences in each pairwise comparison of SD and SNR of four phase images (all P<0.05). There were statistically significant differences of CNR among LD-FBP, LD-DLR and RD-AIDR in four phase images (all P<0.05). The CNR of RD-AIDR was better than that of LD-FBP, and CNR of LD-DLR was better than that of RD-AIDR. DLR algorithm improved the SD, SNR and CNR of four phases of pancreatic images. The improvement of SNR was more significant after contrast enhancement, and the improvement of CNR was more significant in the non-contrast and delay phases. Subjective image scores of different reconstruction images were statistically different in four phase images (all P<0.001). Overall image scores of LD-DLR and RD-AIDR had no significant differences in four phase ( Z value of four phases were 1.00, 2.24, 0.45 and 1.34, respectively; P value of four phases were 0.317, 0.025, 0.655 and 0.180, respectively). Conclusion:The DLR technology can decrease radiation dose of pancreatic CT, improve image quality and satisfy diagnostic requirement. The DLR technology can also reduce image noise, improve the SNR and CNR in low dose contrast-enhanced pancreatic CT.

Objective:To analyze the effects of espO gene knockout on the biological characteristics of enterhemorrhagic Escherichia coli (EHEC). Methods:Two-step methods mediated by the suicide plasmid pCVD442-Δ espO and plasmid pTrc99a were used to construct the espO gene-deleted strain (Δ espO) and the complemented mutant (CΔ espO), respectively. HeLa cells were infected with different EHEC strains to analyze the biological functions and lethal effects of espO gene during infection. Results:PCR, electrophoresis and gene sequencing showed that the Δ espO and CΔ espO mutants were successfully constructed. Compared with the wild-type strain, neither the Δ espO nor CΔ espO mutant showed significant difference in growth rate, indicating that the espO gene had no influence on the growth and replication of EHEC. Furthermore, EspO could activate the tumor necrosis factor receptor (TNF)-induced NF-κB signaling pathway, while the effector protein NleB could inhibit the process. EspO could not inhibit the death of HeLa cells induced by TNF or TNF-related apoptosis-inducing ligand (TRAIL) after EHEC infection. Conclusions:In this study, we successfully constructed the espO gene-deleted and complemented mutants of EHEC and preliminarily analyzed the interaction between espO gene and host cells and the effects of espO gene on cell apoptosis during infection, which provided reference for further research on the in vitro biochemical activity and in vivo pathogenic roles of EspO.

Objective:To investigate the relationship between social support and life satisfaction among the rural elderly,and to explore the moderating and mediating variable between them.Methods:Totally 768 rural elders [aged 60-96 years,average age (70 ±7) years] from Beijing,Hubei and Anhui Province were measured with selfmade General Questionnaire (including self-reported health,rated by five grades from very poor,poor,common,good to very good),self-made Social Support Scale for the Elderly,University of California Los Angeles Loneliness Scale-6 (ULS-6) and Satisfaction with Life Scale (SWLS).Results:Loneliness partly mediated the relationship between social support and life satisfaction and the value of mediating effect was 56.3％.The effect of social support on the rural elders'life satisfaction was moderated by self-evaluated health.Post-hoc analysis indicted that only when the scores of self-evaluated health were lower,social support could predict life satisfaction at a significant level (β =0.25,P ＜0.001).When the scores of self-evaluated health were higher,the predicting effect was not significant (β=0.04,P ＞ 0.05).Conclusion:The relationship between social support and life satisfaction of the rural elderly is mediated by loneliness and moderated by self-evaluated health.

Objective To observe the clinical efficacy of She medicine in treating lumbar intervertebral disc herniation (LIDH) in acute pain stage, and to explore its action mechanism.Method Sixty patients with LIDH in acute pain stage were randomized into a treatment group and a control group, 30 in each group. The treatment group was intervened by She medicine, while the control group was by oral administration of Loxoprofen tablets. Visual Analogue Scale (VAS) was observed before and after intervention, and the clinical efficacies were compared.Result The excellence rate was 83.3% in the treatment group versus 60.0% in the control group, and the difference was statistically significant (P<0.05). The VAS score changed significantly after intervention in both groups (P<0.01). After intervention, there was a significant difference in comparing the VAS score between the two groups (P<0.05).Conclusion She medicine is an effective approach in treating LIDH in acute pain stage, and it can significantly reduce pain.

Objective:To investigate the calcium-phosphate metabolic condition in maintenance hemodialysis patients with chronic kidney disease (CKD), and to observe the effect of large dose calcitriol on secondary hyperparathyroidism (SHPT).
Methods:We tested and compared the serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and alkaline phosphatase (AKP) in hemodialysis patients at different hemodialysis time (Group A with hemodialysis period≤3 years and Group B with hemodialysis period>3 years). We also detected those indexes before and after treating SHPT with large dose calcitriol. Twenty SHPT patients were divided into Group I (enlargement of parathyroid gland or nodule detected by color Doppler ultrasound) and Group II (normal parathyroid gland detected by color Doppler ultrasound).
Results:In the maintenance hemodialysis patients, the serum phosphate was (2.11±0.38) mmol/L and iPTH was (581.11±487.75) pg/mL. The serum level of iPTH in Group B was higher than that in Group A [(828.13±690.39) pg/mL vs (477.94±324.73) pg/mL, P<0.001]. In Group I, the serum level of iPTH [before vs after:(2471.7±898.3) pg/mL vs (2510.4±825.7) pg/mL] and AKP [before vs after:(524.2±18.8)U/L vs (511.3±19.3)U/L] did not change after the treatment of large dose calcitriol (P>0.05). In Group II, the serum level of iPTH [before vs after:(1358.5±302.8) pg/mL vs (369.3±43.4) pg/mL, P<0.001] and AKP [before vs after:(565.9±23.9)U/L vs (234.8±21.1)U/L, P<0.001] decreased signiifcantly after the treatment of large dose calcitriol.
Conclusion:Patients with longer time of hemodialysis have a higher level of iPTH. Large dose calcitriol can improve the clinical syndrome of SHPT, and decrease the level of iPTH and AKP in SHPT patients with normal parathyroid gland.

Objective To study the differential expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitors of metalloproteinase-1(TIMP-1) in serum and decidua tissue from missed abortion and normal first trimester pregnancy,and to explore their function in early pregnancy .Methods The expression of MMP-9,TIMP-1 in serum was determined using enzyme-linked immunosorbent assay ( ELISA) ,and in decidua by immunohistochemical method . Results The MMP-9 serum level from missed abortion women was higher than that from normal first trimester preg -nancy women [(154.60 ±28.69)ng/mL vs.(135.75 ±18.35)ng/mL,t=3.50,P=0.001].The TIMP-1 serum level from missed abortion women was lower than that from normal first trimester pregnancy women [(253.03 ± 29.90)ng/mL vs.(323.15 ±33.62) ng/mL,t=9.86,P=0.000].The MMP-9 positive expression rate in decidua tissue was higher in missed abortion women than that in normal first trimester pregnancy women (82.5%vs.42.5%,χ2 =13.65,P=0.000).The TIMP-1 positive expression rate in decidua tissue was lower in missed abortion women than that in normal first trimester pregnancy women (87.5%vs.62.5%,χ2 =6.67,P=0.010).Conclusion The expression of MMP-9 and TIMP-1 in serum and decidua may be assosiated with missed abortion .