Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.

Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

Challenges and prospects in bridging precision medicine and artificial intelligence in genomic psychiatric treatment

Precision medicine is transforming psychiatric treatment by tailoring personalized healthcare interventions based on clinical,genetic,environmental,and lifestyle factors to optimize medication management.This study investigates how artificial intelligence(AI)and machine learning(ML)can address key challenges in integrating pharmacogenomics(PGx)into psychiatric care.In this integration,AI analyzes vast genomic datasets to identify genetic markers linked to psychiatric conditions.AI-driven models integrating genomic,clinical,and demographic data demonstrated high accuracy in predicting treatment outcomes for major depressive disorder and bipolar disorder.This study also examines the pressing challenges and provides strategic directions for integrating AI and ML in genomic psychiatry,highlighting the importance of ethical considerations and the need for personalized treatment.Effective implementation of AI-driven clinical decision support systems within electronic health records is crucial for translating PGx into routine psychiatric care.Future research should focus on developing enhanced AI-driven predictive models,privacy-preserving data exchange,and robust informatics systems to optimize patient outcomes and advance precision medicine in psychiatry.

Integrating disulfidptosis-related long noncoding RNAs in colorectal cancer prognosis:A path to precision medicine

This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Precision medicine in inflammatory bowel disease:Individualizing the use of biologics and small molecule therapies

The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

DNA methylation as a mediator of epigenetic regulation in the pathogenesis and precision medicine of osteoarthritis:An updated review

The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.

Transcriptome analysis creates a new era of precision medicine for managing recurrent hepatocellular carcinoma

The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies.Over the past few decades,the emergence of transcriptome analysis tools,including real-time quantitative reverse transcription PCR,microarrays,and RNA sequencing,has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures.In recent years,the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment,which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets.In the present article,we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains:primary cancer cells;carcinogenic stimuli;and tumor microenvironment.We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics,surveillance,and treatment of HCC recurrence.

Integration and implementation of precision medicine in the multifaceted inflammatory bowel disease

Inflammatory bowel disease(IBD)is a complex disease with variability in genetic,environmental,and lifestyle factors affecting disease presentation and course.Precision medicine has the potential to play a crucial role in managing IBD by tailoring treatment plans based on the heterogeneity of clinical and temporal variability of patients.Precision medicine is a population-based approach to managing IBD by integrating environmental,genomic,epigenomic,transcriptomic,proteomic,and metabolomic factors.It is a recent and rapidly developing medicine.The widespread adoption of precision medicine worldwide has the potential to result in the early detection of diseases,optimal utilization of healthcare resources,enhanced patient outcomes,and,ultimately,improved quality of life for individuals with IBD.Though precision medicine is promising in terms of better quality of patient care,inadequacies exist in the ongoing research.There is discordance in study conduct,and data collection,utilization,interpretation,and analysis.This review aims to describe the current literature on precision medicine,its multiomics approach,and future directions for its application in IBD.

Personalized immunotherapy in cancer precision medicine

With the significant advances in cancer genomics using next-generation sequencing technologies,genomic and molecular profilingbased precision medicine is used as a part of routine clinical test for guiding and selecting the most appropriate treatments for individual cancer patients.Although many molecular-targeted therapies for a number of actionable genomic alterations have been developed,the clinical application of such information is still limited to a small proportion of cancer patients.In this review,we summarize the current status of personalized drug selection based on genomic and molecular profiling and highlight the challenges how we can further utilize the individual genomic information.Cancer immunotherapies,including immune checkpoint inhibitors,would be one of the potential approaches to apply the results of genomic sequencing most effectively.Highly cancer-specific antigens derived from somatic mutations,the so-called neoantigens,occurring in individual cancers have been in focus recently.Cancer immunotherapies,which target neoantigens,could lead to a precise treatment for cancer patients,despite the challenge in accurately predicting neoantigens that can induce cytotoxic T cells in individual patients.Precise prediction of neoantigens should accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for a broader range of cancer patients.

Status of precision medicine approaches to traumatic brain injury

Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.

Precision medicine for gastrointestinal cancer:Recent progress and future perspective

Gastrointestinal(GI)cancer has a high tumor incidence and mortality rate worldwide.Despite significant improvements in radiotherapy,chemotherapy,and targeted therapy for GI cancer over the last decade,GI cancer is characterized by high recurrence rates and a dismal prognosis.There is an urgent need for new diagnostic and therapeutic approaches.Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer.Here we review the application and status of precision medicine in GI cancer.Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy.With the introduction of gene panels including next-generation sequencing,it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer.Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors,novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs.These progressions will make it feasible to incorporate clinical,genome-based,and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.

Precision medicine: In need of guidance and surveillance

Precision medicine,currently a hotspot in mainstream medicine,has been strongly promoted in recent years. With rapid technological development,such as next-generation sequencing,and fierce competition in molecular targeted drug exploitation,precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine-especially in the prevention and treatment of tumors-is far from satisfactory; however,the aims of precision medicine deserve approval. Thus,this medical approach is currently in its infancy; it has promising prospects,but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs,precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network,integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition,multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support,and its development demands directed momentum. We propose three kinds of impetus(research,application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application.

Pharmacophenomics and Fangjiomics:new pharmacological research paradigm in era of precision medicine

Recent fast advance in biomedical research at the“omic”levels has led to an explosion of big data for the understanding the molecular makeup of diseases,which have revealed the intimate unmatched relationships between the genomic variabilities and the current organ-or system-based definition and classification of disease in Western medi⁃cine.The major challenges in the effort to establish and develop precision medicine are how diseases should be defined and classified in an integrated systemic or omic scale and also on an individualized basis.The phenomics approach to the understanding of diseases will allow the transition from focused phenotype/genotype studies to a systemic largescale phenome and genome,proteome,metabolome approach and the identification of a systemically integrated setof biomarkers for diagnosis and prognosis of disease phenome(or Zhenghou).Phenome-wide associated study(PheWAS)may soon lead the field of medical research and provide insightful and novel clues for redefinition of the disease phenome and its clinical classifications and personalized treatment and ultimately precision medicine.Pharma⁃cophenomics is to characterize the phenomes of drug response and also to identify the corresponding therapeutic targets at the level of systems biology.As a complement of pharmacogenomics/proteomics/metabolomics,pharmacoph⁃enomics offers a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach and refine drug research with systematically-defined drug response and thera⁃peutic targets.Therefore,pharmacophenomics will provide a new paradigm for the study of drug response including effects and toxicities at the level of systems biology and will identify the corresponding therapeutic targets and principles for combination treatment and prevention of disease using Fangji or Fufang that takes into account individual variability in genes,environment,and lifestyle for each person.

Acute myeloid leukemia in the era of precision medicine:recent advances in diagnostic classification and risk stratification

Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

Molecular-targeted therapy toward precision medicine for gastrointestinal caner:Current progress and challenges

Gastrointestinal(GI)cancer remains the deadliest cancer in the world.The current standard treatment for GI cancer focuses on 5-fluorouracil-based chemotherapeutic regimens and surgery,and molecular-targeted therapy is expected to be a more effective and less toxic therapeutic strategy for GI cancer.There is wellestablished evidence for the use of epidermal growth factor receptor-targeted and vascular endothelial growth factor-targeted antibodies,which should routinely be incorporated into treatment strategies for GI cancer.Other potential therapeutic targets involve the PI3K/AKT pathway,tumor growth factor-βpathway,mesenchymal-epithelial transition pathway,WNT pathway,poly(ADP-ribose)polymerase,and immune checkpoints.Many clinical trials assessing the agents of targeted therapy are underway and have presented promising and thoughtprovoking results.With the development of molecular biology techniques,we can identify more targetable molecular alterations in larger patient populations with GI cancer.Targeting these molecules will allow us to reach the goal of precision medicine and improve the outcomes of patients with GI cancer.

Anti-tumor effect of statin on pancreatic adenocarcinoma:From concept to precision medicine

A statin is a cholesterol-lowering agent,which inhibits HMG-CoA(3-hydroxy-3-methylglutaryl-coenzyme A)reductase and subsequently reduces the cholesterol precursor,and was first used commercially in 1987.The concept of cholesterol restriction leading to cancer cell dysfunction was proposed in 1992.The interruption of different signaling pathways has been proved in preclinical experiments to elucidate the anti-tumor mechanism of statins in pancreatic adenocarcinoma.Observational studies have shown that the clinical use of statins is beneficial in patients with pancreatic adenocarcinoma,including a chemoprevention effect,post-surgical resection follow-up and therapeutic prognosis of advanced cancer stage.Arrest of the cancer cell cycle by the combined use of gemcitabine and statin was observed in a cell line study.The effect of microbiota on the tumor microenvironment of pancreatic adenocarcinoma is a new therapeutic approach as statins can modulate the gut microbiota.Hence,further randomized trials of statins in pancreatic adenocarcinoma treatment will be warranted with application of precision medicine from microbiota-derived,cell cycle-based and signaling pathway-targeted research.

Changing paradigm of cancer therapy：precision medicine by next-generation sequencing

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.

Multidisciplinary management of hepatobiliary tumors in the era of precision medicine

Hepatobiliary tumor (HBT), one of the leading causes of cancer deaths globally, is more frequent in East Asia including China [1].HBTincludeslivercancer,cholangiocarcinomaandgallbladder cancer.HBTburdenvariesmarkedlybygenderandgeographic regionduetotheexposureofriskfactors.MajorityofthehepatocellularcarcinomasareassociatedwithhepatitisB-typevirus