1.Analysis of serological and molecular genetic characteristics of a Chinese pedigree with a B(A)06 subtype.
Dongdong TIAN ; Ding ZHAO ; Wei LI ; Zhihao LI ; Jiali YANG ; Yongfang ZHANG ; Liuchuang ZHENG
Chinese Journal of Medical Genetics 2026;43(3):220-227
OBJECTIVE:
To explore the serological and molecular genetic characteristics of a family with subtype B(A)06.
METHODS:
A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036).
RESULTS:
The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family.
CONCLUSION
The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans
;
ABO Blood-Group System/genetics*
;
Female
;
Pedigree
;
Male
;
Infant, Newborn
;
Asian People/genetics*
;
Genotype
;
China
;
Blood Grouping and Crossmatching
;
Hyperbilirubinemia, Neonatal/blood*
;
East Asian People
2.Establishment and clinical application of a method for the determination of three anti-tuberculosis drugs concentrations in plasma of patients with spinal tuberculosis
Yanhong MOU ; Xuehua WU ; Yongfang LI ; Xiaoming CHE
China Pharmacy 2026;37(1):72-76
OBJECTIVE To establish a method for simultaneously determining three anti-tuberculosis drugs in the plasma of patients with spinal tuberculosis and apply it in clinical practice. METHODS LC-MS/MS method was established for the quantitative determination of the concentrations of isoniazid, rifampicin and pyrazinamide in the plasma of patients with spinal tuberculosis, using diphenhydramine as the internal standard. The determination was carried out using Chemalink CM-C18T column, with mobile phase consisting of 0.1% formic acid-methanol solution (gradient elution), at the flow rate of 0.4 mL/min and an injection volume of 2 μL. Multiple reaction monitoring was conducted using an electrospray ionization source in positive ion mode. The ion pairs used for quantitative analysis were m/z 138.0→121.0( for isoniazid), m/z 823.3→791.3( for rifampicin), m/z 124.1→ 79.0 (for pyrazinamide), and m/z 256.0→167.0 (for diphenhydramine). Fifty-three patients diagnosed with spinal tuberculosis in Qinghai Provincial People’s Hospital from January 2023 to June 2025 were selected, and the plasma concentrations of isoniazid, rifampicin and pyrazinamide in these patients were measured using the above method. RESULTS The linear ranges for isoniazid, rifampicin and pyrazinamide were 0.5-16, 2-64, and 2.5-80 μg/mL, respectively (r≥0.998 7). The accuracy ranged from 90.20% to 108.64% (n=5). RSDs for intra-day precision were all less than 6.63% (n=5), while those for inter-day precision were all less than 8.42% (n=3). The matrix effects ranged from 88.60% to 115.41% (n=5). The relative deviations in the stability tests were all within the ±15% range, and the carry-over effect did not interfere with the determination. The results of clinical application showed that the mean plasma drug concentrations of isoniazid, rifampicin and pyrazinamide in patients with spinal tuberculosis were (3.62±2.80), (8.55±4.57), and (20.12±6.56) μg/mL, respectively. The incidences of plasma drug concentrations falling below the effective peak concentrations were 49.06%, 58.49% and 60.38%, respectively. CONCLUSIONS The method established in this study is rapid, accurate, and demonstrates good stability, making it suitable for clinical monitoring of the plasma concentrations of isoniazid, rifampicin and pyrazinamide in patients with spinal tuberculosis.
3.Study on the Mechanism of Tongluo Baoshen Decoction Intervening IgA Nephropathy Rats
Yongfang LIU ; Rui HUANG ; Huiyang LIU ; Jianfeng DAI ; Yinghua LIU ; Xingyu LIU ; Zhiying FENG ; Tiantian YIN ; Li ZHOU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):105-113
Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.
4.Clinical observation of ivabradine in the treatment of chronic heart failure in end-stage renal disease patients undergoing maintenance hemodialysis
Gang TAN ; Yongfang LI ; Guangpeng ZHOU
China Pharmacy 2025;36(1):91-95
OBJECTIVE To investigate the efficacy and safety of ivabradine in the treatment of end-stage renal disease patients with chronic heart failure (CHF) during maintenance hemodialysis (MHD).METHODS End-stage renal disease patients with CHF during MHD who were treated in our hospital from May 2021 to September 2023 and met the inclusion criteria were selected as the study subjects.They were randomly divided into control group and observation group,with 60 cases in each group,using a random number table method.Both groups of patients received MHD three times a week for 4 hours each time and were anticoagulated with low-molecular weight heparin sodium.At the same time,they were treated with CHF conventional therapy;based on the above treatment,observation group was orally administered Ivabradine tablets 5 mg,twice a day (if the resting heart rate was above 60 beats/min after 2 weeks,the drug dose was increased to 7.5 mg,twice a day).Both groups of patients were treated continuously for 6 months.The clinical efficacy of 2 groups was compared as well as vital signs,cardiac function,the levels of heart failure-related biomarkers and inflammatory factors before and after treatment,and the incidences of dialysis-related hypotension and adverse drug reactions.RESULTS The effective rate of the observation group (92.45%) was significantly higher than that of the control group (76.47%),and the incidence of dialysis-related hypotension (20.75%) was significantly lower than that of the control group (41.18%) (P<0.05).The heart rate,the levels of left ventricular end-systolic diameter,left ventricular end-diastolic diameter,serum N-terminal pro-B-type natriuretic peptide,cancer antigen 125,tumor necrosis factor-α,interleukin-6,and hypersensitive C-reactive protein in observation group after treatment were significantly lower than those of control group (P<0.05);the left ventricular ejection fraction and cardiac output were significantly higher than those in the control group (P<0.05).There was no statistically significant difference in the diastolic blood pressure,systolic blood pressure,or the total incidence of adverse drug reactions between the two groups after treatment (P>0.05).CONCLUSIONS Ivabradine can significantly improve cardiac function,inhibit ventricular remodeling,down-regulate serum levels of serum N-terminal pro-B-type natriuretic peptide and cancer antigen 125,decrease body inflammation levels and the incidence of dialysis-related hypotension in end-stage renal disease patients with CHF during MHD,with significant clinical effects and good safety.
5.Exploration on the Pharmacodynamic Material Basis of Bawei Chenxiang Powder in Treating Coronary Heart Disease Based on Network Pharmacology and Experimental Verification
Yinghuan LI ; Yaqiong QI ; Yongfang LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(1):69-77
Objective To investigate the pharmacodynamic material basis of Bawei Chenxiang Powder in the treatment of coronary heart disease.Methods The action targets of 16 blood-entry components of Bawei Chenxiang Powder were retrieved by TCMSP,PharmMapper and SwissTargetPrediction,and the disease targets were found by GeneCards and OMIM databases,which screened the intersection targets of the components and the disease;a component-target network was constructed using Cytoscape 3.9.1 software and key components were screened;the protein-protein interaction network was obtained by using STRING database and core targets were screened;GO and KEGG pathway enrichment analysis of intersecting targets was performed using DAVID database;molecular docking between key components and core targets was performed;molecular dynamics simulations were performed using Amber 20 software;UPLC-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry was used to quantify the key components in rat plasma;the hypoxia/reoxygenation model of H9c2 cells was constructed to investigate the effects of the key components on the survival rate and LDH of H9c2 cells.Results Totally 514 targets of the 16 blood-entry components of Bawei Chenxiang Powder,1716 targets of coronary heart disease,and 192 intersecting targets were retrieved,among which the key components were quercetin,kaempferol,naringenin,dehydrodiisoeugenol,and the core targets were ALB,IL6,TNF,GAPDH,AKT1,IL1B and TP53;the KEGG results showed that the mechanism of Bawei Chenxiang Powder for treating coronary heart disease may be related to PI3K-Akt signaling pathway,MAPK signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,etc.;molecular docking showed that the key components had low binding energy with the core targets;molecular dynamics simulation results showed that the binding energy of TNF and quercetin was tight and stable,with a binding energy of-20.263 3 kcal/mol;the concentrations of the key components in plasma were quercetin(15.65±1.76)ng/mL,kaempferol(10.58±0.96)ng/mL,naringenin(3.07±0.69)ng/mL,and dehydrodiisoeugenol(4.90±1.18)ng/mL;the results of cellular experiments showed that the above four components could significantly increase the survival rate of H9c2 cells under hypoxia/reoxygenation conditions and reduce the LDH activity in the cell supernatant.Conclusion Quercetin,kaempferol,naringenin,dehydrodiisoeugenol and other components in Bawei Chenxiang Powder may be the pharmacodynamic material basis for treating coronary heart disease.
6.Study on the Mechanism of Tongluo Baoshen Decoction in Regulating Gprc5b/NF-κB/NLRP3 Pathway to Improve Podocyte Injury in IgA Nephropathy Rats
Yongfang LIU ; Li ZHOU ; Huiyang LIU ; Jianfeng DAI ; Yinghua LIU ; Bangming CHEN ; Xuefei LIN ; Taiwang YANG ; Xingyu LIU ; Yi FU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):112-120
Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.
7.Study on the Mechanism of Tongluo Baoshen Decoction Intervening IgA Nephropathy Rats
Yongfang LIU ; Rui HUANG ; Huiyang LIU ; Jianfeng DAI ; Yinghua LIU ; Xingyu LIU ; Zhiying FENG ; Tiantian YIN ; Li ZHOU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):105-113
Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.
8.Investigation on the quality standard of pharmaceutical excipient steviol glycosides
Yongfang LI ; Qing YANG ; Cancan DING ; Qiao ZHANG ; Zhizhou JIANG ; Yongfu XIE ; Yuanyuan LI ; Shuai HUANG
Drug Standards of China 2025;26(5):527-532
Objective:To propose suggestions for the revision of quality standard of steviol glycosides through research on its major manufacturer's products.Methods:The inspection items in the current quality standards were inspected,with domestic and international quality standard of steviol glycosides.Results:Specific rotation was from-33.39° to-39.50°,pH was from 5.3 to 6.7,impurity absorbency was lower than 0.096 0,while the contents of weight loss on drying were lower than 5.0%,residue on ignition were lower than 0.043%,methanol residual were lower than 0.01%,ethanol residual were lower than 0.06%,residue on arsenic were lower than 0.000 054%,lead wasn't detected.The content of rebaudioside A and 13 kinds of steviol glycosides were 8.23%-68.48%and 85.78%-96.13%.Conclusion:The main components of the commercial steviol glycosides products were rebaudioside A and stevioside,with low safety risk of elemental impurities and solvent residues.It provided suggestions for the revision of quality standard of steviol glycosides in the Chinese Pharmacopoeia.
9.Adaptive multi-view learning method for enhanced drug repurposing using chemical-induced transcriptional profiles,knowledge graphs,and large language models
Yudong YAN ; Yinqi YANG ; Zhuohao TONG ; Yu WANG ; Fan YANG ; Zupeng PAN ; Chuan LIU ; Mingze BAI ; Yongfang XIE ; Yuefei LI ; Kunxian SHU ; Yinghong LI
Journal of Pharmaceutical Analysis 2025;15(6):1354-1369
Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.
10.Study on the Mechanism of Tongluo Baoshen Decoction in Regulating Gprc5b/NF-κB/NLRP3 Pathway to Improve Podocyte Injury in IgA Nephropathy Rats
Yongfang LIU ; Li ZHOU ; Huiyang LIU ; Jianfeng DAI ; Yinghua LIU ; Bangming CHEN ; Xuefei LIN ; Taiwang YANG ; Xingyu LIU ; Yi FU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):112-120
Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.

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