1.A computational medicine framework integrating multi-omics, systems biology, and artificial neural networks for Alzheimer's disease therapeutic discovery.
Yisheng YANG ; Yizhu DIAO ; Lulu JIANG ; Fanlu LI ; Liye CHEN ; Ming NI ; Zheng WANG ; Hai FANG
Acta Pharmaceutica Sinica B 2025;15(9):4411-4426
The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.
2.Prediction of Quality Markers of Alismatis Rhizoma and Salted Alismatis Rhizoma Based on Fingerprint and Network Pharmacology
Ting HONG ; Dan LI ; Yu ZHANG ; Yan ZHANG ; Yisheng YANG ; Xiaowu XIAO
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):135-141
Objective To predict the quality markers of Alismatis Rhizoma and salted Alismatis Rhizoma based on fingerprints and multivariate statistical analysis combined with network pharmacology.Methods HPLC-DAD method was used to establish fingerprints of Alismatis Rhizoma and salted Alismatis Rhizoma.Based on the peak area data of the fingerprints,clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were employed to evaluate the quality of 10 batches of Alismatis Rhizoma and 12 batches of salted Alismatis Rhizoma.The main components with quality differences were screened.Network pharmacology was used to analyze the targets and related pathways of the screened components,A component-target-pathway network was constructed,and molecular docking was used to verify.Quality markers of Alismatis Rhizoma and salted Alismatis Rhizoma were predicted.Results The HPLC fingerprints of Alismatis Rhizoma and salted Alismatis Rhizoma were established.The similarity evaluation showed that the similarity of 10 batches of Alismatis Rhizoma and 12 batches of salted Alismatis Rhizoma ranges from 0.991 to 0.998,0.992 to 1.000,respectively.Nine components with quality differences were identified through multivariate statistical analysis,and five of them were identified as alismoxide,alisol C,alismol,alisol B,23-acetate alisol B.Network pharmacological analysis suggested 278 targets of action associated with the five components.The main signaling pathways of KEGG pathway enrichment analysis were closely related to the main efficacy and modern pharmacological effects of Alismatis Rhizoma and salted Alismatis Rhizoma.These 5 components were preliminary predicted as quality markers for Alismatis Rhizoma and salted Alismatis Rhizoma.Conclusion This study predicted 5 quality markers for Alismatis Rhizoma and salted Alismatis Rhizoma,which can provide reference for their quality control and further research.
3.Gut microbiota diversity and characteristic microbiota in patients with different histopathological subtypes of lung cancer
Yang LYU ; Liangliang BAO ; Yisheng HE ; Mo YANG ; Lihao CHEN
Journal of Clinical Medicine in Practice 2025;29(14):18-22
Objective To explore the differences in gut microbiota among different histopathologi-cal subtypes of lung cancer.Methods A total of 80 lung cancer patients admitted to the Department of Oncology and Hematology of Anqing First People's Hospital from February 2020 to February 2024 were selected as study subjects.Meanwhile,80 healthy volunteers who underwent physical examina-tions during the same period were selected as control group.According to pathological examination re-sults,the lung cancer patients were divided into three subgroups:lung squamous cell carcinoma group,lung adenocarcinoma group,and lung small-cell cancer group.The 16S ribosomal RNA(16S rRNA)sequencing technology was used to compare the differences in gut microbiota diversity and the characteristics of species relative abundance between lung cancer patients with different patho-logical grades and the control group.Results The proportion of patients with a family history of lung cancer was higher in different lung cancer subtypes than in the control group,and the difference was statistically significant(P<0.05).The abundance-based coverage estimator(ACE)index,Simpson index,and Shannon index of patients with different lung cancer pathological subtypes were all lower than those in the control group,and the differences were statistically significant(P<0.05).β-diver-sity analysis showed that there were significant differences in the variation of gut microbial community structure between the control group and lung cancer patients with different pathological types(P<0.05).The results of LEfSe indicated that there were differences in gut characteristic microbiota among patients with different pathological subtypes.Specifically,Megamonas was enriched in the LUAD group,Butyrivibrio was enriched in the LSCC group,and Akkermansia was enriched in the SCLC group.Conclusion There are significant differences in the composition of gut microbiota between lung cancer patients and the normal population,and the gut microbiota of patients with different lung cancer pathological subtypes have distinct characteristics.These differences may provide new bio-markers and therapeutic strategies for the diagnosis and treatment of lung cancer.
4.Prediction of Quality Markers of Alismatis Rhizoma and Salted Alismatis Rhizoma Based on Fingerprint and Network Pharmacology
Ting HONG ; Dan LI ; Yu ZHANG ; Yan ZHANG ; Yisheng YANG ; Xiaowu XIAO
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):135-141
Objective To predict the quality markers of Alismatis Rhizoma and salted Alismatis Rhizoma based on fingerprints and multivariate statistical analysis combined with network pharmacology.Methods HPLC-DAD method was used to establish fingerprints of Alismatis Rhizoma and salted Alismatis Rhizoma.Based on the peak area data of the fingerprints,clustering analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were employed to evaluate the quality of 10 batches of Alismatis Rhizoma and 12 batches of salted Alismatis Rhizoma.The main components with quality differences were screened.Network pharmacology was used to analyze the targets and related pathways of the screened components,A component-target-pathway network was constructed,and molecular docking was used to verify.Quality markers of Alismatis Rhizoma and salted Alismatis Rhizoma were predicted.Results The HPLC fingerprints of Alismatis Rhizoma and salted Alismatis Rhizoma were established.The similarity evaluation showed that the similarity of 10 batches of Alismatis Rhizoma and 12 batches of salted Alismatis Rhizoma ranges from 0.991 to 0.998,0.992 to 1.000,respectively.Nine components with quality differences were identified through multivariate statistical analysis,and five of them were identified as alismoxide,alisol C,alismol,alisol B,23-acetate alisol B.Network pharmacological analysis suggested 278 targets of action associated with the five components.The main signaling pathways of KEGG pathway enrichment analysis were closely related to the main efficacy and modern pharmacological effects of Alismatis Rhizoma and salted Alismatis Rhizoma.These 5 components were preliminary predicted as quality markers for Alismatis Rhizoma and salted Alismatis Rhizoma.Conclusion This study predicted 5 quality markers for Alismatis Rhizoma and salted Alismatis Rhizoma,which can provide reference for their quality control and further research.
5.Finite element analysis of the correlation between tilt angle of titanium cage and postoperative subsidence of titanium cage after anterior subtotal cervical corpectomy,decompression and fusion
Zhifei LI ; Yin YANG ; Hualong CHEN ; Qinqiu LIANG ; Yuanming ZHONG ; Yisheng ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(9):1313-1319
BACKGROUND:Anterior subtotal corpectomy,decompression and fusion is a conventional method to treat cervical degenerative diseases.A titanium cage is an important implant to maintain the stability of the cervical spine after subtotal corpectomy.In recent years,many patients have complications such as titanium cage sinking,which are highly controversial. OBJECTIVE:To investigate the internal biomechanical relationship between the tilt angle of the titanium cage and postoperative titanium cage subsidence after anterior subtotal cervical corpectomy,decompression and fusion. METHODS:A three-dimensional finite element model of the C4-C6 segment was established by CT images of a normal human cervical spine,in which the anterior subtotal resection,decompression and fusion of the C5 vertebral body were simulated,and titanium cages with different tilt angles(-6° to-1° negative angle,that is,the front edge of titanium cage is shorter than the rear edge of titanium cage;1° to 6° positive angle,that is,the front edge of titanium cage is longer than the rear edge of titanium cage)were placed.After setting the boundary conditions,preloads of 50,100 and 150 N were applied respectively on the C4 vertebral body.The stress value of each contact point between the titanium cage and C4 lower-end plate and C6 lower-end plate(seven stress contact points on the contact surface of titanium mesh)was recorded and statistical analysis was conducted. RESULTS AND CONCLUSION:(1)The tilt angles of the titanium cage of the positive angle group and negative angle group under 50,100 and 150 N stress respectively were found by Mann Whitn test,with P<0.05,which was statistically significant.The dispersion coefficients of the positive angle group were smaller than those of the negative angle group under 50,100 and 150 N stress conditions.(2)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the positive angle group of titanium cage tilt angle found that when the angle was set to 1° to 5°,the difference was not statistically significant(P>0.05).However,when the tilt angle of the titanium cage was set to 6°,the difference was statistically significant(P<0.05).(3)Under 50,100 and 150 N stress conditions,the Wilcoxon sign rank test in the negative angle group of titanium cage tilt angle found that when the tilt angle was set to-1° to-6°,the difference was not statistically significant(P>0.05).(4)It is concluded that in the sagittal position,the titanium cage with a positive tilt angle is more stable than with a negative tilt angle,which is more suitable for clinical use.The tilt angle of the titanium cage is relatively stable in the range of 1° to 5°.When the tilt angle is 6°,the stability starts to decline,which is easy to cause complications of titanium cage sinking after surgery.It is more suitable to select the titanium cage with a tilt angle of 1° to 5° according to the clinical situation during surgery to improve the efficacy.
6.Practice and effect of construction of rational drug use mode of PIVAS by the activities of quality control circle
Yun LU ; Gao WU ; Peng FU ; Yisheng FAN ; Ting YANG ; Shanshan LIU
Journal of Pharmaceutical Practice 2023;41(9):566-571
Objective To establish a rational drug use model of PIVAS and promote the rational drug use in clinical practices by enhancing the quality of prescription review by pharmacists. Methods The PIVAS physician orders received from 2014 to 2021 were extracted through the hospital information management (HIS) system. The types of irrational physician orders were statistically analyzed, the improvements were made by the method of quality control circle (QCC). Results The model of PIVAS rational drug use formed a standardized process. The proficiency of physician order review was improved. From 2014 to 2021, the number and proportion of unreasonable physician orders in PIVAS decreased year by year. Every type of unreasonable physician orders was improved year by year. Conclusion The professional and technical levels of pharmacist for physician order review at our hospital were improved by the model of PIVAS rational drug use. The quality of pharmaceutical service was significantly improved which ensured the safety of patients' medication.
7.Analysis on the medication rules of Pu Ji Fang for treating acne externally based on data mining
Yisheng ZHANG ; Jundong ZHANG ; Xue LI ; Xinyuan LIU ; Jianan YANG ; Zongyou LI ; Ping SONG
International Journal of Traditional Chinese Medicine 2023;45(2):208-213
Objective:To analyze the medication rules in the ancient book Pu Ji Fang for the external treatment of acne based on data mining method. Methods:By screening out the methods of treating acne externally in Pu Ji Fang and establishing a standardized medical record database, this paper adopted the web version of Ancient and Modern Medical Record Cloud Platform to calculate the frequency, properties, flavors, and meridians of those medicines, and conduct cluster analysis by using IBM SPSS Modeler 18.0 software to analyze the association rules. Results:A total of 87 prescriptions were selected, including 164 kinds of Chinese materia medica, among which. Radix Angelicae, Ligusticum Wallichii, Rhizoma Typhoni and lead powder are frequently appeared. The properties of those medicines are mainly warm, cold and mild; the flavors of those medicines are mainly spicy, acrid, sweet and bitter, and the meridians mainly belongs to lung, spleen, stomach and liver meridians. The medical pair and group with the strongest associationion are Ligusticum Wallichii- Radix Angelicae and Rhizoma Typhonii- Radix Angelicae- Ligusticum Wallichii. Those freuently appeared medicines could be grouped into three categories. The paste dosage that was frequently appeared has strong correlation with tallow, mercury and lead powder, while the powder dosage that was frequenctly appeared has strong correlation with Angelica Dahurica, Radix Saponicae, Gleditsia sinensis, Radices Ligustici Sinensis and Ligusticum Wallichii. Conclusions:The application of data mining method could preliminarily reveal the medication rules of Pu Ji Fang for the external treatment of acne. The main treatment method is XinSanFaYue. The three categories of Chinese materia medica are used to treat the syndrome of asthenic habitus attacked by exogenous pathogenic factors, exterior attacked by wind heat and hot blood stasis respectively, showing the rules of treating acne externally before Ming Dynasty and providing references for the clinical treatment of acne.
8.Evaluation index research of the randomized controlled trial of infertility treated by Traditional Chinese Medicine
Jundong ZHANG ; Jiangfeng LIU ; Yisheng ZHANG ; Xinyuan LIU ; Qi CHENG ; Shuo YANG
International Journal of Traditional Chinese Medicine 2023;45(4):492-497
Objective:To collect and analyze the evaluation index of infertility treated by Traditional Chinese Medicine (TCM), which will lay a foundation for the establishment of the core index and evaluation index system of TCM treating infertility.Methods:By retriving the published literatures of randomized controlled trials of infertility treated by TCM in the database of CNKI, VIP, Wanfang, SinoMed, PubMed and Cochrane Library from January 1, 2011 to December 31, 2020, and after the screening according to the creteria of inclusion and exclusion, this paper analyzed the normal indexes of infertility and the pathogenic indexes of TCM.Results:A total of 95 RCTs were included, including 9 069 patients aged between 20-39 years old. The average sample size of each RCT study was 95, involving 78 evaluation criteria. The highest frequency of use was the total effective rate, etiological-index analysis found that the general indicators of infertility such as the total effective rate, pregnancy rate, TCM syndrome scores,and common etiological factors such as LH, FSH are the characteristic indicators.Conclusion:There are many problems in the evaluation indexes of clinical trials of treating infertility by TCM, such as great differences in number and not standardized usage. It is necessary to carry out research on the construction of core indicator and evaluation indicator systems of infertility according to different etiologies.
9.Clinical Efficiency and Safety of Hypofractionated Thoracic Radiotherapy Combined with EP Chemotherapy on Patients with Limited-stage Small-cell Lung Cancer
Yisheng HE ; Liangliang BAO ; Jiawen YU ; Yang LYU
Cancer Research on Prevention and Treatment 2023;50(2):170-174
Objective To investigate the efficacy and safety of hypofractionated thoracic radiotherapy combined with EP chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC). Methods A total of 117 patients with LS-SCLC were enrolled and randomly divided into test group (
10.The interaction between 5-HTT gene rs6354 polymorphism and family factors on the adaptability of Mongolian school-age children
Yang XIAO ; Man ZHAO ; Yisheng YANG ; Yuling LI
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(6):548-552
Objective:To explore the effects of rs6354 polymorphism of 5-HTT gene and family factors on the adaptability of Mongolian school-age children.Methods:The adaptability of 453 primary school students was assessed based on the middle childhood temperament questionnaire(MCTQ). The polymorphism of 5-HTT gene rs6354 was determined by improved multiple ligase detection reaction(iMLDR) technology. SPSS18.0 statistical software was used for data processing and analysis.Results:(1) The adaptability scores of children with GG/GT and TT genotype at rs6354 locus of 5-HTT gene were(2.88±0.73) and(3.03±0.76). (2) Univariate analysis showed that the adaptability scores of Mongolian school-age children were significantly different among different education levels of their parents (father F=2.580, P=0.037; mother F=3.245, P=0.012). (3) Multiple regression analysis showed that mother's educational level( B=-0.079, P=0.010) and rs6354 polymorphism( B=0.165, P=0.041) were inflencing factors of the adaptability score of Mongolian school-age children. (4) Logistic regression analysis showed that father's education level was a significant impact factor of the adaptive level of Mongolian school-age children( B=0.453, P<0.05, OR=1.573, 95% CI=1.023-2.417). Conclusion:rs6354 polymorphism is weakly correlated with children's adaptability, and the education level of parents, especially fathers, may be an important factor affecting the adaptability of Mongolian school-age children.

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