1.Construction and verification of humanized mouse model of IL - 9R CDS gene
Chong Liu ; Yuanyuan Zhou ; Hui Xue ; Zimeng Xue ; Weile Chen ; Jiajie Tu
Acta Universitatis Medicinalis Anhui 2025;60(6):1015-1021
Objective :
To construct a humanized mouse model of the interleukin-9 receptor(IL-9R) coding DNA sequence(CDS) gene and to verify the genotype and IL-9R expression in mice.
Methods :
The CRISPR/Cas9 genome editing technology was used to replace the exon 2-7 fragment of the il-9r gene in mouse embryonic stem cells with the corresponding human IL-9R sequence. After verifying the completion of the gene fragment replacement, tetraploid embryos were constructed and microinjected back into the oviducts of surrogate mice. Through surrogacy by female mice, homozygous humanized mice were obtained. DNA was extracted from the homozygous humanized mice IL-9R CDS gene, and their genotypes were identified by agarose gel electrophoresis after PCR amplification. Western blot was used to detect the expression of IL-9R in the spleen and thymus of homozygous humanized mice with either wild-type(WT) or IL-9R gene humanization.
Results :
Gel electrophoresis after PCR amplification showed that mice with only a 1 805 bp band amplified using WT primers were wild-type, while mice with 2 553 bp and 2 340 bp bands amplified using 5KI and 3KI primers, respectively, were homozygous humanized mice with IL-9R CDS gene. Western blot results indicated that the tissues of homozygous humanized mice model with IL-9R CDS gene expressed IL-9R significantly.
Conclusion
The humanized mouse model with IL-9R CDS gene has been successfully constructed and characterized.
2.Exploring the Effect of Indigo on Lipopolysaccharide-Induced HaCaT Cells Through the AhR/NLRP3 Signaling Pathway
Haiqing LEI ; Yu LIN ; Muchen XU ; Jiyuan ZHENG ; Weile HUANG ; Lihong YANG ; Ling HAN ; Jing LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2831-2839
Objective To investigate the effect of indigo on inflammatory factors and the aryl hydrocarbon receptor(AhR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in lipopolysaccharide(LPS)-induced keratinocytes(HaCaT cells).Methods An LPS-induced HaCaT cell model was established,and experimental groups were set as follows:blank group,model group,indigo group,AhR agonist(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)group,AhR inhibitor(CH-223191)group,and indigo+AhR inhibitor group.The Cell Counting Kit-8(CCK-8)assay was used to detect the effects of different concentrations of indigo,TCDD,and CH-223191 on HaCaT cell viability after 24 hours of intervention.Quantitative real-time PCR(qPCR)was employed to measure the mRNA expression levels of interleukin-1β(IL-1β),nuclear factor kappa B(NF-κB),tumor necrosis factor-α(TNF-α),AhR,cytochrome P450 family 1 subfamily A member 1(CYP1A1),NLRP3,Caspase-1,and apoptosis-associated speck-like protein(ASC)in each group.Western Blot analysis was used to assess changes in the cellular localization of AhR protein expression.Results(1)The IC50 of indigo intervention in HaCaT cells was 118.7 μmol·L-1.Treatment with different concentrations of CH-223191 and TCDD for 24 hours had no significant effect on HaCaT cell viability.(2)Compared with the model group,the indigo group showed decreased mRNA expression levels of IL-1β,NF-κB,NLRP3,and Caspase-1(P<0.05 or P<0.000 1),while the mRNA expression levels of AhR and CYP1A1 were significantly increased(P<0.05 or P<0.000 1).(3)Compared with the blank group,the indigo group reduced cytoplasmic AhR protein expression and increased nuclear AhR protein expression(P<0.001 or P<0.000 1).(4)Compared with the model group,both the indigo group and the AhR agonist group significantly increased AhR mRNA expression levels(P<0.05),while the AhR inhibitor group decreased AhR and CYP1A1 mRNA expression levels(P<0.05)and increased IL-1β and NLRP3 mRNA expression levels(P<0.05).(5)Compared with the AhR inhibitor group,the indigo+AhR inhibitor group showed increased mRNA expression levels of AhR and CYP1A1(P<0.05)and decreased mRNA expression levels of NLRP3,Caspase-1,and IL-1β(P<0.05).Conclusion Indigo reduces inflammatory factors in LPS-induced HaCaT cells and participates in inhibiting the occurrence and development of psoriasis by activating AhR to negatively regulate the NLRP3 inflammasome.
3.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.
4.A case-control study on association between shift work and type 2 diabetes mellitus
Can LIU ; Jing FAN ; Weile WU ; Wenjiong LIANG ; Yulong LIAN ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(7):827-832
Background With economic development and globalization, shift work has become prevalent across industries. Its relationship with type 2 diabetes mellitus (T2DM) attracts increasing attention. Objective To thoroughly explore the relationship between shift work and T2DM, and analyze the impacts of specific shift patterns on T2DM, so as to provide a basis for formulating reasonable shift schedules. Methods We conducted a 1:2 matched case-control study among adults (20-60 years) who ordered occupational health examinations at the Wuxi No.8 People's Hospital from November to December 2023. The case group comprised 200 T2DM patients, while the controls were 400 age-stratified matched non-diabetic individuals. General demographic characteristics, behavioral habits, medical history, and shift work exposure data (including shift patterns, frequency, and length of service) 5 years prior to diagnosis were collected through standardized questionnaires. Logistic regression adjusted for selected confounders was employed to evaluate the association between shift work and T2DM. Results The logistic regression analysis demonstrated that shift work was associated with an increased risk of T2DM. After adjusting for confounding factors, shift workers had a 3.55 times higher risk of being diagnosed T2DM compared to non-shift workers (OR=3.55, 95%CI: 1.026, 12.263). The risk varied across different shift patterns, and the three-shift two-rotation system showed the highest risk (OR=4.17, 95%CI: 1.921, 9.035), followed by the two-shift system (OR=2.94, 95%CI: 2.016, 4.281) and four-shift three-rotation system (OR=2.66, 95%CI: 1.611, 6.093). Workers with more than 3 monthly shift days had a 2.74-fold increased risk (95%CI: 1.658, 4.512) compared to non-shift workers. Additionally, working more than 8 h daily (OR=1.74, 95%CI: 1.185, 2.562) and having more than 20 years of service (OR=2.51, 95%CI: 1.581, 3.976) were both significantly associated with a higher T2DM risk. The trend tests revealed that each incremental increase in monthly shift days and length of service elevated T2DM risk by 2.61 times (95%CI: 1.813, 3.765) and 1.49 times (95%CI: 1.147, 1.931), respectively (P<0.05). Conclusion Shift work is an independent risk factor for T2DM, with three-shift two-rotation system posing the highest risk. Shift frequency, daily working hours, and length of service are all significant factors affecting the risk of T2DM. These findings support industry-specific shift policy reform and targeted glucose monitoring and health interventions are recommended for workers engaged in high-risk shift patterns (e.g., three-shift two-rotation system, frequent shifts) and those with prolonged shift work history (>20 years).
5.Correlation of systemic immune inflammatory index and monocyte-to-lymphocyte ratio with chronic kidney disease-mineral and bone disorder in patients with chronic kidney disease
Wei ZHONG ; Shihua SHEN ; Weile WANG ; Jingjing LIU ; Yiya WANG ; Wei ZHU ; Jing YANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(6):841-846
Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.
6.Analysis of factors associated with intradialytic hypotension in patients undergoing hemodialysis
Chenchen YANG ; Shihua SHEN ; Weile WANG ; Jingjing LIU ; Yiya WANG ; Wei ZHU ; Jing YANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(6):859-864
Objective:To analyze the risk factors associated with intradialytic hypotension (IDH) in patients undergoing maintenance hemodialysis (MHD).Methods:This study used a cross-sectional design and included 150 adult patients who underwent MHD at The Third Affiliated Hospital of Anhui Medical University from January 2023 to March 2024. Relevant clinical data were collected to analyze the occurrence of IDH in patients undergoing MHD over 3 months, and the associated risk factors.Results:Among the 150 patients undergoing MHD, there were 67 in the IDH group and 83 in the non-IDH group. The IDH group had a higher fibrinogen/albumin ratio (FAR) [89.41 (73.30, 114.50) vs. 76.56 (65.80, 89.60), χ2 = -3.55, P < 0.001], an older age [(68.46 ± 14.10) years vs. (61.30 ± 12.23) years, t = -3.33, P = 0.001], a longer dialysis duration [(4 (3.5, 4.0) hours vs. (4 (4.0, 4.0) hours), U = -2.11, P = 0.044], a greater ultrafiltration volume [(2.20 ± 0.74) L vs. (1.92 ± 0.82) L, t = -2.16, P = 0.032], a higher ultrafiltration rate [(8.90 ± 2.64) mL·h?1·kg?1 vs. (7.75 ± 2.91) mL·h?1·kg?1, t = -2.51, P = 0.013], and a higher ultrafiltration volume/dry body mass ratio [(33.75 ± 9.76) mL/kg vs. (30.21 ± 11.39) mL/kg, t = -2.11, P = 0.046] compared with the non-IDH group. In the IDH group, the proportion of patients with primary chronic glomerulonephritis was lower (19.4% vs. 37.3%, χ2 = 5.76, P = 0.016), fibrinogen levels were higher [(3.63 (3.15, 4.50) μg/L vs. (3.34 (2.90, 3.74) μg/L, U = -2.61, P = 0.009], albumin levels were lower [(41.26 ± 4.03) g/L vs. (43.42 ± 4.29) g/L, t = 3.15, P = 0.002], high-density lipoprotein cholesterol (HDL-C) levels were lower [0.90 (0.77, 1.09) mmol/L vs. 1.05 (0.84, 1.34) mmol/L, U = -2.77, P = 0.006], and C-reactive protein levels were higher [5.92 (2.79, 9.61) mg/L vs. 2.70 (0.99, 6.49) mg/L, U = -2.27, P = 0.023] compared with the non-IDH group. Multivariate logistic regression analysis indicated that higher FAR values ( OR = 1.030, P = 0.025), a history of chronic glomerulonephritis ( OR = 10.408, P = 0.012), older age ( OR = 1.062, P = 0.043), a high ultrafiltration volume/dry body mass ratio ( OR = 1.072, P = 0.037), and low HDL-C levels ( OR = 0.046, P = 0.015) are independent risk factors for IDH. The area under the receiver operating characteristic curve for FAR predicting IDH was 0.699 (95% CI: 0.571-0.827, P = 0.003). The combination of age, chronic glomerulonephritis, ultrafiltration volume/dry body mass ratio, HDL-C levels, and FAR for predicting IDH resulted in a receiver operating characteristic curve area of 0.839 (95% CI: 0.750-0.929, P < 0.001). Conclusions:Among the risk factors for IDH in patients undergoing MHD, FAR is independently associated with an increased risk of IDH and serves as a valuable predictor for its occurrence in these patients.
7.Correlation of systemic immune inflammatory index and monocyte-to-lymphocyte ratio with chronic kidney disease-mineral and bone disorder in patients with chronic kidney disease
Wei ZHONG ; Shihua SHEN ; Weile WANG ; Jingjing LIU ; Yiya WANG ; Wei ZHU ; Jing YANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(6):841-846
Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.
8.Analysis of factors associated with intradialytic hypotension in patients undergoing hemodialysis
Chenchen YANG ; Shihua SHEN ; Weile WANG ; Jingjing LIU ; Yiya WANG ; Wei ZHU ; Jing YANG
Chinese Journal of Primary Medicine and Pharmacy 2025;32(6):859-864
Objective:To analyze the risk factors associated with intradialytic hypotension (IDH) in patients undergoing maintenance hemodialysis (MHD).Methods:This study used a cross-sectional design and included 150 adult patients who underwent MHD at The Third Affiliated Hospital of Anhui Medical University from January 2023 to March 2024. Relevant clinical data were collected to analyze the occurrence of IDH in patients undergoing MHD over 3 months, and the associated risk factors.Results:Among the 150 patients undergoing MHD, there were 67 in the IDH group and 83 in the non-IDH group. The IDH group had a higher fibrinogen/albumin ratio (FAR) [89.41 (73.30, 114.50) vs. 76.56 (65.80, 89.60), χ2 = -3.55, P < 0.001], an older age [(68.46 ± 14.10) years vs. (61.30 ± 12.23) years, t = -3.33, P = 0.001], a longer dialysis duration [(4 (3.5, 4.0) hours vs. (4 (4.0, 4.0) hours), U = -2.11, P = 0.044], a greater ultrafiltration volume [(2.20 ± 0.74) L vs. (1.92 ± 0.82) L, t = -2.16, P = 0.032], a higher ultrafiltration rate [(8.90 ± 2.64) mL·h?1·kg?1 vs. (7.75 ± 2.91) mL·h?1·kg?1, t = -2.51, P = 0.013], and a higher ultrafiltration volume/dry body mass ratio [(33.75 ± 9.76) mL/kg vs. (30.21 ± 11.39) mL/kg, t = -2.11, P = 0.046] compared with the non-IDH group. In the IDH group, the proportion of patients with primary chronic glomerulonephritis was lower (19.4% vs. 37.3%, χ2 = 5.76, P = 0.016), fibrinogen levels were higher [(3.63 (3.15, 4.50) μg/L vs. (3.34 (2.90, 3.74) μg/L, U = -2.61, P = 0.009], albumin levels were lower [(41.26 ± 4.03) g/L vs. (43.42 ± 4.29) g/L, t = 3.15, P = 0.002], high-density lipoprotein cholesterol (HDL-C) levels were lower [0.90 (0.77, 1.09) mmol/L vs. 1.05 (0.84, 1.34) mmol/L, U = -2.77, P = 0.006], and C-reactive protein levels were higher [5.92 (2.79, 9.61) mg/L vs. 2.70 (0.99, 6.49) mg/L, U = -2.27, P = 0.023] compared with the non-IDH group. Multivariate logistic regression analysis indicated that higher FAR values ( OR = 1.030, P = 0.025), a history of chronic glomerulonephritis ( OR = 10.408, P = 0.012), older age ( OR = 1.062, P = 0.043), a high ultrafiltration volume/dry body mass ratio ( OR = 1.072, P = 0.037), and low HDL-C levels ( OR = 0.046, P = 0.015) are independent risk factors for IDH. The area under the receiver operating characteristic curve for FAR predicting IDH was 0.699 (95% CI: 0.571-0.827, P = 0.003). The combination of age, chronic glomerulonephritis, ultrafiltration volume/dry body mass ratio, HDL-C levels, and FAR for predicting IDH resulted in a receiver operating characteristic curve area of 0.839 (95% CI: 0.750-0.929, P < 0.001). Conclusions:Among the risk factors for IDH in patients undergoing MHD, FAR is independently associated with an increased risk of IDH and serves as a valuable predictor for its occurrence in these patients.
9.Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic,Clinical and Immunological Characteristics in Cancers
Wang JIAOJIAO ; Liao YONG ; Yang PINGLIAN ; Ye WEILE ; Liu YONG ; Xiao CHUNXIA ; Liao WEIXIONG ; Chen CHUNBO ; Liu ZHIPING ; Huang ZUNNAN
Biomedical and Environmental Sciences 2024;37(7):698-715
Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman's analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.
10.Not Available.
Weile YE ; Jiaojiao WANG ; Peter J LITTLE ; Jiami ZOU ; Zhihua ZHENG ; Jing LU ; Yanjun YIN ; Hao LIU ; Dongmei ZHANG ; Peiqing LIU ; Suowen XU ; Wencai YE ; Zhiping LIU
Acta Pharmaceutica Sinica B 2024;14(1):1-19
Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.


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