Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

Objective:To explore the impact of Epstein-Barr Virus(EBV) infection on treatment response and survival in newly diagnosed multiple myeloma(MM).Methods:The clinical data of 196 patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from June 1st, 2019 to February 25th,2021 were analyzed retrospectively and divided into EBV-positive group (106 cases) and negative group (90 cases) according to the primary EBV DNA results in peripheral blood mononuclear cells.To analyse the distribution of EBV positive rates in each type and in each stage of the Revised International Staging System (R-ISS), and to compare EBV DNA loads in EBV-positive patients among R-ISS stages.Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis between the two groups.The clinical prognosis of EBV-positive patients was summarized through survival analysis and Cox regression.Results:The EBV positive rate in patients with newly diagnosed MM was 54% (106/196), with the highest rate in patients with κ light chain type (9/12).Patients with R-ISS stage Ⅲ had a significantly higher positive rate than with stage Ⅰ ( χ2=4.68, P=0.031) and stage Ⅱ ( χ2=6.04, P=0.014), but there was no significant difference in EBV DNA loads between EBV-positive MM patients by stage ( Z=3.27, P=0.195).Serum creatinine (Scr) and β 2-microglobulin (β 2-MG) levels were higher in the EBV-positive group than in the EBV-negative group ( Z=1.98, P=0.048 and Z=2.08, P=0.038), and the occurrence of t(4;14) was also higher in the EBV-positive group ( χ2=3.93, P=0.047).The proportion of complete response (CR)/stringent complete response(sCR) and very good partial response(VGPR) after completion of the fourth chemotherapy were significantly lower in the EBV-positive group than in the EBV-negative group ( χ2=12.82, P=0.001 and χ2=8.30, P=0.004), and a higher rate of progressive disease (PD) occurred in the EBV-positive group ( χ2=4.48, P=0.046).The 2-year progression-free survival (PFS) of MM patients was shorter in the EBV-positive group compared to that in the EBV-negative group ( Z=-4.50, P0.01).Cox regression analysis showed that R-ISS stage Ⅲ ( HR=5.38, 95% CI 1.28-22.56, P=0.021), failure to achieve VGPR after the fourth chemotherapy ( HR=3.02, 95% CI 1.42-6.46, P=0.004), EBV-positive ( HR=1.98, 95% CI 1.02-3.87, P=0.045), with 1q21 amplification ( HR=2.35, 95% CI 1.16-4.75, P=0.017) and 13q14 deletion ( HR=1.93, 95% CI 1.01-3.67, P=0.046) were independent risk factors for PFS in newly diagnosed MM. Conclusions:EBV infection is an independent risk factor for poor prognosis, which has important clinical implications for the outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Objective:To explore the protective effect and mechanism of irisin on liver injury and mitochondrial dysfunction of hepatocytes in mice with acute necrotizing pancreatitis (ANP).Methods:24 mice were randomly divided into the control group, the ANP group, the irisin group and the cilengitide group, with 6 mice in each group. The ANP group was prepared by intraperitoneal injection of 20% L-arginine. The irisin group was injected with 250 μg/kg of irisin intraperitoneally on the basis of the induction of ANP. The cilengitide group was injected with the integrin receptor αVβ3/5 inhibitor cilengitide at 20 mg/kg on the basis of the treatment of the irisin group. The control group was injected with 0.9% normal saline instead of L-arginine. Routine liver histopathological examination and scoring were performed; immunohistochemical staining was used to detect the level of neutrophil infiltration in liver tissue; the ultrastructure changes of mitochondria were observed under transmission electron microscopy; biochemistry was used to detect the ATP content in liver tissue to reflect the changes in mitochondrial function; the total antioxidant capacity of liver tissue was detected by the ferric reducing/antioxidant power (FRAP) method; the DHE fluorescence probe labeling method was used to detect the accumulation degree of oxygen free radicals in liver tissue.Results:The livers of the control group showed no obvious abnormalities. However, the ANP group, the irisin group and the cilengitide group all had liver tissue damage and infiltration of inflammatory cells in the mice. Compared with the ANP group, the liver pathological score, the number of neutrophil infiltration, and the DHE fluorescence staining density in the irisin group were significantly lower [(3.40±0.72) vs (7.26±1.01) points, (14.67±2.51) vs (33.33±3.51) cells, (16.33±5.03) vs (50.33±10.69) cells], while the above indicators in the cilengitide group were all increased [(7.06±1.55) points, (40.33±5.03) cells, (51.00±12.8) cells]; the ATP content [(296.04±64.6), (54.77±18.05), (109.50±56.61), (40.29±11.68) μmol/gprot], and the antioxidant capacity [(0.19±0.01), (0.10±0.01), (0.17±0.02), (0.11±0.01) mmol/g] in the control group, ANP group, irisin group and cilengitide group changed accordingly. The above differences were statistically significant (all P value <0.05). Transmission electron microscopy observation revealed that the abnormal mitophagy of liver cells in the irisin group restored to normal, while the mitophagy abnormality in the cilengitide group was exacerbated. Conclusions:Irisin could improve the disordered mitochondrial function and oxidative stress in liver cells by acting on integrin receptors αVβ3/5, thereby alleviating liver damage and inflammatory responses in ANP mice.

Objective:To explore the protective effect and mechanism of irisin on liver injury and mitochondrial dysfunction of hepatocytes in mice with acute necrotizing pancreatitis (ANP).Methods:24 mice were randomly divided into the control group, the ANP group, the irisin group and the cilengitide group, with 6 mice in each group. The ANP group was prepared by intraperitoneal injection of 20% L-arginine. The irisin group was injected with 250 μg/kg of irisin intraperitoneally on the basis of the induction of ANP. The cilengitide group was injected with the integrin receptor αVβ3/5 inhibitor cilengitide at 20 mg/kg on the basis of the treatment of the irisin group. The control group was injected with 0.9% normal saline instead of L-arginine. Routine liver histopathological examination and scoring were performed; immunohistochemical staining was used to detect the level of neutrophil infiltration in liver tissue; the ultrastructure changes of mitochondria were observed under transmission electron microscopy; biochemistry was used to detect the ATP content in liver tissue to reflect the changes in mitochondrial function; the total antioxidant capacity of liver tissue was detected by the ferric reducing/antioxidant power (FRAP) method; the DHE fluorescence probe labeling method was used to detect the accumulation degree of oxygen free radicals in liver tissue.Results:The livers of the control group showed no obvious abnormalities. However, the ANP group, the irisin group and the cilengitide group all had liver tissue damage and infiltration of inflammatory cells in the mice. Compared with the ANP group, the liver pathological score, the number of neutrophil infiltration, and the DHE fluorescence staining density in the irisin group were significantly lower [(3.40±0.72) vs (7.26±1.01) points, (14.67±2.51) vs (33.33±3.51) cells, (16.33±5.03) vs (50.33±10.69) cells], while the above indicators in the cilengitide group were all increased [(7.06±1.55) points, (40.33±5.03) cells, (51.00±12.8) cells]; the ATP content [(296.04±64.6), (54.77±18.05), (109.50±56.61), (40.29±11.68) μmol/gprot], and the antioxidant capacity [(0.19±0.01), (0.10±0.01), (0.17±0.02), (0.11±0.01) mmol/g] in the control group, ANP group, irisin group and cilengitide group changed accordingly. The above differences were statistically significant (all P value <0.05). Transmission electron microscopy observation revealed that the abnormal mitophagy of liver cells in the irisin group restored to normal, while the mitophagy abnormality in the cilengitide group was exacerbated. Conclusions:Irisin could improve the disordered mitochondrial function and oxidative stress in liver cells by acting on integrin receptors αVβ3/5, thereby alleviating liver damage and inflammatory responses in ANP mice.

Objective:To explore the effects of astragaloside (Ast) on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and excitation-inhibition balance in amygdala of mice with autism spectrum disorder(ASD).Methods:The C57BL/6 pregnant mice in model group were intraperitoneally injected with sodium valproate(500 mg/kg) on days 12-13 of pregnancy, while the C57BL/6 pregnant mice in control group were given an equal volume of 0.9% NaCl solution.The offspring mice were then divided into 5 groups according to the nest matching principle: the control+ normal saline group(Con+ NS group), the control+ Ast group (Con+ Ast group), the model+ normal saline group(Mod+ NS group), the model+ Ast group (Mod+ Ast group) and the Model+ Ast+ PI3K inhibitor LY294002 group (Mod+ Ast+ LY group), with 12 mice in each group. At the age of 14 days, the mice in the Con+ Ast group and the Mod+ Ast group were intraperitoneally injected with Ast (20 mg/kg, once a day for 7 consecutive days), the mice in the Mod+ Ast+ LY group were intraperitoneally injected with Ast (20 mg/kg) and LY294002(30 mg/kg), the mice in Con+ NS group and Mod+ NS group were intraperitoneally injected with the same volume of 0.9% NaCl solution.The depressive-like behavior and social function were evaluated by the marble-burying test (MBT), the three-chamber social interaction test(SIT), and the forced swimming test(FST). The expression levels of proteins related to the PI3K/AKT signaling pathway in the amygdala were detected by Western blot. The immunofluorescence method was employed to determine the levels of the neurotransmitters glutamate (Glu) and γ-aminobutyric acid(GABA)in the amygdala region.Statistical analysis was carried out using GraphPad Prism 9.5.0 software, and one-way ANOVA test was utilized for comparisons among multiple groups.Results:(1)Behavioral results showed that there were statistically significant differences in the number of buried beads of the MBT, the social interaction index and social novelty preference index of the SIT, and the immobility time and first immobile state incubation period of the FST among the five groups( F=28.85, 89.23, 77.62, 91.70, 125.40, all P<0.05). The number of buried beads and immobility time in Mod+ NS group were higher than those in Con+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Con+ NS group (all P<0.05). The number of buried beads and immobility time in Mod+ Ast group were lower than those in Mod+ NS group, and first immobile state incubation period, the social interaction index and social novelty preference index were higher than those in Mod+ NS group(all P<0.05). The number of buried beads and immobility time in Mod+ Ast+ LY group were higher than those in Mod+ Ast group, and first immobile state incubation period, the social interaction index and social novelty preference index were lower than those in Mod+ Ast group (all P<0.05).(2) Western blot results showed that there were statistically significant differences in p-PI3K/PI3K, p-AKT/AKT in amygdala among the five groups ( F=27.14, 25.50, both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ NS group were lower than those of Con+ NS group(both P<0.05).The expressions of p-PI3K/PI3K and p-AKT/AKT in amygdala of Mod+ Ast group((0.67±0.04), (0.52±0.09))were higher than those of Mod+ NS group((0.48±0.06), (0.34±0.06))(both P<0.05). The expressions of p-PI3K/PI3K and p-AKT/AKT in the amygdala of Mod+ Ast+ LY group ((0.52±0.04), (0.36±0.10))were lower than those of Mod+ Ast group(both P<0.05). (3)Immunofluorescence results showed that the number of Glu- and GABA- positive cells in the amygdala region of the five groups were significantly different( F=41.84, 37.70, both P<0.05). The number of Glu-positive cells in the amygdala of Mod+ NS group was higher than that of Con+ NS group, and the number of GABA-positive cells in Mod+ NS group was lower than that of Con+ NS group( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast group((54.00±8.48)cells/mm 2)was lower than that of Mod+ NS group((82.17±7.36)cells/mm 2), and the number of GABA-positive cells in Mod+ Ast group((59.20±11.22)cells/mm 2)was higher than that of Mod+ NS group((41.33±7.11)cells/mm 2) ( P<0.05). The number of Glu-positive cells in the amygdala of Mod+ Ast+ LY group((75.67±9.15)cells/mm 2) was higher than that of Mod+ Ast group, and the number of GABA-positive cells in Mod+ Ast+ LY group((43.33±4.27)cells/mm 2)was lower than that of Mod+ Ast group ( P<0.05). Conclusion:Astragaloside can ameliorate social deficits in ASD mice via modulating the PI3K/AKT signaling pathway and excitation-inhibition balance in the amygdala.

AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23％ (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00％ (95％CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14％ (95％CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17％(95％CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38％ (95％CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.