Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal fo...Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal focus in the pharmaceutical industry.RNAi drugs are extensively utilized in the treatment of chronic and rare diseases due to their exceptional gene-silencing efficiency,manageable side effects,and straightforward synthesis process.This study undertook a thorough analysis of the global landscape of RNAi drug patents,highlighting the latest technological advancements and trends.We meticulously identified and cataloged the key technologies that dominated this patent landscape.The goal was to provide valuable insights and references for researchers involved in the development of RNAi drugs within the domestic pharmaceutical sector.展开更多
The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three ...The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.展开更多
The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for ident...The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),d...This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),daphnane-type(237),and aconitine-type diterpene alkaloids(265)with rich biological activities reported in 2013-2023.And the drugs in clinical use or under clinical investigation of diterpenoids and leading compounds were summarized.展开更多
The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medici...The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medicinal product and re-evaluation of generic medicinal product.In China,RLDs are sourced from various origins,but their quality and market availability can be constrained by multiple factors,including emergent issues such as nitrosamine impurities.Five classes of medicinal products have been reported to be at risk for containing nitrosamine impurities:sartan-based medicines,metformin-containing products,ranitidine medicines,rifampicin medicines,and Champix.This paper explores the control strategies implemented by drug regulatory agencies in the United States and the European Union to manage nitrosamine impurities and assesses their impact on the market availability and quality of RLDs in China.The aim is to offer valuable insights for generic drug manufacturers and regulatory bodies both domestically and internationally.展开更多
Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the si...Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.展开更多
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety...Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.展开更多
With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and charact...With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.展开更多
AIM:To assess and rank the efficacy of various nonsteroidal anti-inflammatory drugs(NSAIDs)in preventing postoperative macular edema(PME)after cataract surgery.METHODS:A comprehensive search was conducted across PubMe...AIM:To assess and rank the efficacy of various nonsteroidal anti-inflammatory drugs(NSAIDs)in preventing postoperative macular edema(PME)after cataract surgery.METHODS:A comprehensive search was conducted across PubMed,Embase,Cochrane Library,and Web of Science databases.Randomized controlled trials(RCTs)comparing different NSAIDs and control treatments for the prevention of PME were included.Data from the studies were synthesized using the“gemtc”package in R.Risk of bias was assessed with the Cochrane RoB 2 tool,and heterogeneity was evaluated using the global I2 statistic.Surface under the cumulative ranking curve(SUCRA)values were calculated for each treatment.RESULTS:Of 132 identified records,9 RCTs met the inclusion criteria.The Network Meta-analysis indicated that nepafenac had the highest efficacy in preventing PME,followed by artificial tear substitute,ketorolac,diclofenac,and bromfenac.The league table comparisons and rankograms corroborated these findings,with nepafenac consistently ranking highest.Heterogeneity analysis yielded high I2 values,indicating substantial variability across studies.CONCLUSION:This Network Meta-analysis suggests that nepafenac is the most effective NSAID for preventing PME following cataract surgery.Given the substantial heterogeneity observed,further high-quality RCTs are required to confirm these findings and explore the sources of variability.Clinicians should consider these results when selecting NSAIDs for PME prophylaxis in cataract surgery patients.展开更多
Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safet...Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.展开更多
The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases re...The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases reported in our hospital from January 1,2022,to December 31,2023,an analysis was conducted.Statistical analysis of the data revealed that 72.73%of these ADR incidents occurred in a hospital setting.The incidence of ADRs was higher in female patients compared to males,with the majority of cases(59.14%)observed in individuals aged 51-70 years.Intravenous administration was the predominant route linked to ADRs,accounting for 69.66%of the cases.Serious ADRs represented 9.30%of the total,including one instance where symptoms did not improve despite drug discontinuation or treatment.Cytotoxic antineoplastic drugs were responsible for 97.85%of all ADRs,with oxaliplatin being the most frequently implicated agent(19.82%).Gastrointestinal system involvement was the most common ADR manifestation,observed in 60.79%of cases.These findings underscored the necessity of enhanced monitoring for ADRs associated with cytotoxic antineoplastic drugs,particularly platinum-based agents.Comprehensive risk assessments and tailored treatment plans should be implemented during chemotherapy to minimize the occurrence of ADRs and safeguard patient safety.展开更多
Background Hypertension is associated with an increased risk of calcific aortic valve stenosis(CAVS).However,the directionality of causation between blood pressure traits and aortic stenosis is unclear,as is the benef...Background Hypertension is associated with an increased risk of calcific aortic valve stenosis(CAVS).However,the directionality of causation between blood pressure traits and aortic stenosis is unclear,as is the benefit of antihypertensive drugs for CAVS.Methods Using genome-wide association studies(GWAS)summary statistics,we performed bidirectional two-sample univariable mendelian randomization(UVMR)to assess the causal associations of systolic blood pressure(SBP),diastolic blood pressure(DBP),and pulse pressure(PP)with CAVS.Multivariable mendelian randomization(MVMR)was conducted to evaluate the direct effect of hypertension on CAVS,adjusting for confounders.Drug target mendelian randomization(MR)and summary-level MR(SMR)were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk.Inverse variance weighting was the primary MR method,with sensitivity analyses to validate results.Results UVMR showed SBP,DBP,and PP have causal effects on CAVS,with no significant reverse causality.MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders.Drug-target MR analyses indicated that calcium channel blockers(CCBs),loop diuretics,and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk.SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk,while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk.Conclusions Hypertension has a causal relationship with CAVS.Managing SBP in hypertensive patients with CCBs may prevent CAVS.ARBs might exert protective effects on CAVS independent of blood pressure reduction.The relationship between diuretics and CAVS is complex,with opposite effects through different mechanisms.展开更多
Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide ev...Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide evidence for improving policies and promoting rational drug use.Methods:The study was based on data from the China National Health Insurance Agency that spanned January 2019 to December 2020.Descriptive analysis was conducted using volume and expenditure as variables.Interrupted time series analysis was applied to further analyze Chinese patent medicines.Results:The unit prices of atorvastatin and rosuvastatin decreased by 25%-96%,whereas the prices of Zhibitai and Xuezhikang fluctuated slightly.The affordability is measured as the monthly expenditure on treatment divided by the daily wage.After policy implementation,the affordability of atorvastatin and rosuvastatin improved from 0.242 to 0.014 and from 0.247 to 0.019,respectively.The defined daily doses(DDDs)for atorvastatin and rosuvastatin also increased,whereas total expenditures decreased in hospitals of all levels.Both at the national level and at all levels of hospital,the policy had no significant impact on expenditures for Zhibitai and Xuezhikang and their defined daily doses.Conclusions:The NVBP saved costs in the short term by incorporating high-quality,widely used lipid-lowering drugs.Notably,the policy impacted lipid-lowering chemical drugs,whereas Chinese patent medicines remained largely unaffected.Doctors'use of Chinese patent medicines did not decline,highlighting the clinical specificity of these medicines.展开更多
Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, ...Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.展开更多
1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and co...1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and constitutes a major global health problem.^([1])The number of new cases in China accounted for 46.6%of the global liver cancer cases,and 47.1%of the global liver cancer deaths occurred in China.^([2])展开更多
Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prom...Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transderm...Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.展开更多
Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as rema...Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as remarkable advances have been achieved which are all highly depended on drug development.Under the current requirements to high production capacity and novel synthesis methods of drugs,green synthesis based on strategies with different ways of empowering,advanced catalysts and unique reaction equipment are attracting huge attention and of great challenging.Higher quality products and environmentally friendly synthesis conditions are becoming more and more important for manufacturing process which has new requirements for catalyst materials and synthesis processes.Polyoxometalates(POMs)are class of transition metals-oxygen clusters with precise molecular structures and superior physicochemical properties which have made longstanding and important applications upon research community of functional materials,catalysis and medicine.In this review,the recent advances of polyoxometalates based strategies for green synthesis of drugs are summarized including POMs based catalysts,alternative reaction equipment based novel synthesis protocols.The significance of POMs to pharmaceutical and industrial field is highlighted and the related perspective for future development are well discussed.展开更多
文摘Nucleic acid drugs represent the third wave of innovation in drug research and development,succeeding small-molecule and antibody drugs.These drugs,particularly RNA interference(RNAi)therapies,have become a pivotal focus in the pharmaceutical industry.RNAi drugs are extensively utilized in the treatment of chronic and rare diseases due to their exceptional gene-silencing efficiency,manageable side effects,and straightforward synthesis process.This study undertook a thorough analysis of the global landscape of RNAi drug patents,highlighting the latest technological advancements and trends.We meticulously identified and cataloged the key technologies that dominated this patent landscape.The goal was to provide valuable insights and references for researchers involved in the development of RNAi drugs within the domestic pharmaceutical sector.
基金supported by the National Medical Products Administration Commissioned Research Project (No.20211440216)the National Administration of Traditional Chinese Medicine Science and Technology Project (No.GZY-KJS-2024-03)+3 种基金the State Key Laboratory of Drug Regulatory Science Project (No.2023SKLDRS0104)the Basic Research Program Natural Science Fund-Frontier Leading Technology Basic Research Special Project of Jiangsu Province (No.BK20232014)the Programs Foundation for Leading Talents in National Administration of Traditional Chinese Medicine of China“Qihuang scholars”Projectthe Tianjin Administration for Market Regulation Science and Technology Key Projects (No.2022-W35)。
文摘The research and development of new traditional Chinese medicine(TCM)drugs have progressively established a novel system founded on the integration of TCM theory,human experience,and clinical trials(termed the“Three Combinations”).However,considering TCM's distinctive features of“syndrome differentiation and treatment”and“multicomponent formulations and complex mechanisms”,current TCM drug development faces challenges such as insufficient understanding of the material basis and the overall mechanism of action and an incomplete evidence chain system.Moreover,significant obstacles persist in gathering human experience data,evaluating clinical efficacy,and controlling the quality of active ingredients,which impede the innovation process in TCM drug development.Network pharmacology,centered on the“network targets”theory,transcends the limitations of the conventional“single target”reductionist research model.It emphasizes the comprehensive effects of disease or syndrome biological networks as targets to elucidate the overall regulatory mechanism of TCM prescriptions.This approach aligns with the holistic perspective of TCM,offering a novel method consistent with TCM's holistic view for investigating the complex mechanisms of TCM and developing new TCM drugs.It is internationally recognized as a“next-generation drug research model”.To advance the research of new tools,methods,and standards for TCM evaluation and to overcome fundamental,critical,and cutting-edge technical challenges in TCM regulation,this consensus aims to explore the characteristics,progress,challenges,applicable pathways,and specific applications of network pharmacology as a new theory,method,and tool in TCM drug development.The goal is to enhance the quality of TCM drug research and development and accelerate the efficiency of developing new TCM products.
文摘The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
文摘This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),daphnane-type(237),and aconitine-type diterpene alkaloids(265)with rich biological activities reported in 2013-2023.And the drugs in clinical use or under clinical investigation of diterpenoids and leading compounds were summarized.
基金Subject construction funding project of Institute for Chemical Drug Control(Grant No.2024HYZX42)in National Institutes for Food and Drug Control,Beijing,China。
文摘The Reference Listed drug(RLD)plays a critical role in the development and research of generic medicinal products,serving as the comparator product used in the marketing authorization application of new generic medicinal product and re-evaluation of generic medicinal product.In China,RLDs are sourced from various origins,but their quality and market availability can be constrained by multiple factors,including emergent issues such as nitrosamine impurities.Five classes of medicinal products have been reported to be at risk for containing nitrosamine impurities:sartan-based medicines,metformin-containing products,ranitidine medicines,rifampicin medicines,and Champix.This paper explores the control strategies implemented by drug regulatory agencies in the United States and the European Union to manage nitrosamine impurities and assesses their impact on the market availability and quality of RLDs in China.The aim is to offer valuable insights for generic drug manufacturers and regulatory bodies both domestically and internationally.
文摘Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications,particularly in oncology.This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023.With a focus on recent research findings,the review explores the rich biodiversity of marine organisms,including sponges,corals,algae,and microorganisms,which have yielded numerous compounds exhibiting promising anticancer properties.Emphasizing the multifaceted mechanisms of action,the review discusses the molecular targets and pathways targeted by these compounds,such as cell cycle regulation,apoptosis induction,angiogenesis inhibition,and modulation of signaling pathways.Additionally,the review highlights the innovative strategies employed in the isolation,structural elucidation,and chemical modification of marine natural products to enhance their potency,selectivity,and pharmacological properties.Furthermore,it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs,including issues related to supply,sustainability,synthesis,and clinical translation.Finally,the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy.
基金supported by the National Natural Science Foundation of China (Nos. 82173674 and 82204195)。
文摘Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future,aiming to provide valuable insights and references for the continued advancement of peptidebased drugs.
文摘With the continuous advancement of cancer treatment methods, plasma combined with drug therapy has garnered widespread attention as an emerging therapeutic strategy. This paper elaborates on the generation and characteristics of plasma, as well as its mechanisms of action on cancer cells when used alone, including the production of reactive oxygen and nitrogen species, and damage to cancer cell membranes, and organelles. It emphasizes the synergistic mechanisms observed when plasma is combined with various anticancer drugs (e.g., chemotherapeutic agents, targeted drugs, and immunotherapies). The analysis focuses on enhancing drug uptake, promoting the activation of drug action targets, and improving the tumor microenvironment. These insights provide a theoretical basis for optimizing plasma-drug combination therapy for cancer.
基金Supported by Natural Science Foundation of Chongqing(No.CSTB2024NSCQ-MSX0900No.CSTB2023NSCQ-MSX0593).
文摘AIM:To assess and rank the efficacy of various nonsteroidal anti-inflammatory drugs(NSAIDs)in preventing postoperative macular edema(PME)after cataract surgery.METHODS:A comprehensive search was conducted across PubMed,Embase,Cochrane Library,and Web of Science databases.Randomized controlled trials(RCTs)comparing different NSAIDs and control treatments for the prevention of PME were included.Data from the studies were synthesized using the“gemtc”package in R.Risk of bias was assessed with the Cochrane RoB 2 tool,and heterogeneity was evaluated using the global I2 statistic.Surface under the cumulative ranking curve(SUCRA)values were calculated for each treatment.RESULTS:Of 132 identified records,9 RCTs met the inclusion criteria.The Network Meta-analysis indicated that nepafenac had the highest efficacy in preventing PME,followed by artificial tear substitute,ketorolac,diclofenac,and bromfenac.The league table comparisons and rankograms corroborated these findings,with nepafenac consistently ranking highest.Heterogeneity analysis yielded high I2 values,indicating substantial variability across studies.CONCLUSION:This Network Meta-analysis suggests that nepafenac is the most effective NSAID for preventing PME following cataract surgery.Given the substantial heterogeneity observed,further high-quality RCTs are required to confirm these findings and explore the sources of variability.Clinicians should consider these results when selecting NSAIDs for PME prophylaxis in cataract surgery patients.
基金supported by the Independent Research and Development Projects Foundation of Shanghai InnoStar Bio-Techology Co.,Ltd.(H23ZZYF01 and H24ZZYF01).
文摘Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.
基金Collaborative Innovation Program of Jiangsu Pharmaceutical Vocational College(Grant No.20239120)。
文摘The aim of this study is to evaluate the characteristics and patterns of adverse drug reactions(ADRs)associated with antineoplastic drugs and provide insights for safer chemotherapy practices.Based on 979 ADR cases reported in our hospital from January 1,2022,to December 31,2023,an analysis was conducted.Statistical analysis of the data revealed that 72.73%of these ADR incidents occurred in a hospital setting.The incidence of ADRs was higher in female patients compared to males,with the majority of cases(59.14%)observed in individuals aged 51-70 years.Intravenous administration was the predominant route linked to ADRs,accounting for 69.66%of the cases.Serious ADRs represented 9.30%of the total,including one instance where symptoms did not improve despite drug discontinuation or treatment.Cytotoxic antineoplastic drugs were responsible for 97.85%of all ADRs,with oxaliplatin being the most frequently implicated agent(19.82%).Gastrointestinal system involvement was the most common ADR manifestation,observed in 60.79%of cases.These findings underscored the necessity of enhanced monitoring for ADRs associated with cytotoxic antineoplastic drugs,particularly platinum-based agents.Comprehensive risk assessments and tailored treatment plans should be implemented during chemotherapy to minimize the occurrence of ADRs and safeguard patient safety.
基金supported by the National Natural Science Foundation of China(82170375,U23A20395)1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University(ZYGD23021,23HXF-H009)Sichuan Science and Technology Program 2023NSFSC1645。
文摘Background Hypertension is associated with an increased risk of calcific aortic valve stenosis(CAVS).However,the directionality of causation between blood pressure traits and aortic stenosis is unclear,as is the benefit of antihypertensive drugs for CAVS.Methods Using genome-wide association studies(GWAS)summary statistics,we performed bidirectional two-sample univariable mendelian randomization(UVMR)to assess the causal associations of systolic blood pressure(SBP),diastolic blood pressure(DBP),and pulse pressure(PP)with CAVS.Multivariable mendelian randomization(MVMR)was conducted to evaluate the direct effect of hypertension on CAVS,adjusting for confounders.Drug target mendelian randomization(MR)and summary-level MR(SMR)were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk.Inverse variance weighting was the primary MR method,with sensitivity analyses to validate results.Results UVMR showed SBP,DBP,and PP have causal effects on CAVS,with no significant reverse causality.MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders.Drug-target MR analyses indicated that calcium channel blockers(CCBs),loop diuretics,and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk.SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk,while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk.Conclusions Hypertension has a causal relationship with CAVS.Managing SBP in hypertensive patients with CCBs may prevent CAVS.ARBs might exert protective effects on CAVS independent of blood pressure reduction.The relationship between diuretics and CAVS is complex,with opposite effects through different mechanisms.
基金funded by the Beijing Natural Science Foundation(grant number 9232010)Capital's Funds for Health Improvement and Research(grant number 2022-2-4079).
文摘Background:Atherosclerotic cardiovascular disease remains the leading cause of death worldwide.This study aims to explore the impact of national volume-based procurement(NVBP)on Chinese patent medicines and provide evidence for improving policies and promoting rational drug use.Methods:The study was based on data from the China National Health Insurance Agency that spanned January 2019 to December 2020.Descriptive analysis was conducted using volume and expenditure as variables.Interrupted time series analysis was applied to further analyze Chinese patent medicines.Results:The unit prices of atorvastatin and rosuvastatin decreased by 25%-96%,whereas the prices of Zhibitai and Xuezhikang fluctuated slightly.The affordability is measured as the monthly expenditure on treatment divided by the daily wage.After policy implementation,the affordability of atorvastatin and rosuvastatin improved from 0.242 to 0.014 and from 0.247 to 0.019,respectively.The defined daily doses(DDDs)for atorvastatin and rosuvastatin also increased,whereas total expenditures decreased in hospitals of all levels.Both at the national level and at all levels of hospital,the policy had no significant impact on expenditures for Zhibitai and Xuezhikang and their defined daily doses.Conclusions:The NVBP saved costs in the short term by incorporating high-quality,widely used lipid-lowering drugs.Notably,the policy impacted lipid-lowering chemical drugs,whereas Chinese patent medicines remained largely unaffected.Doctors'use of Chinese patent medicines did not decline,highlighting the clinical specificity of these medicines.
文摘Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.
基金Supported by a grant from the Talent Exchange Service Center of National Health Commission(RCLX2315049)。
文摘1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and constitutes a major global health problem.^([1])The number of new cases in China accounted for 46.6%of the global liver cancer cases,and 47.1%of the global liver cancer deaths occurred in China.^([2])
文摘Background:immune checkpoint inhibitors(ICIs)have revolutionized the treatment of metastatic urothelial carcinoma(mUC),significantly improving survival outcomes.However,a subset of patients do not respond to ICIs,prompting research into potential predictive factors.Commonly prescribed medications such as corticosteroids,proton-pump inhibitors(PPIs),antibiotics(Abs),antihypertensives,and analgesics may influence ICI effectiveness.Methods:we conducted a literature search on PubMed to investigate the impact of concomitant medications on the outcomes of patients with mUC,treated with ICIs.We selected the most relevant studies and performed a narrative review.Results:corticosteroids,PPIs and Abs have been associated with reduced survival in ICI-treated patients,including those with mUC.In contrast,antihypertensive agents like renin-angiotensin system inhibitors and betablockers may enhance ICI efficacy,though evidence remains inconclusive.The impact of other medications,such as statins,metformin,and analgesics,on ICI outcomes is less clear,with some data suggesting a detrimental impact on immune response.Conclusions:this narrative review synthesizes current evidence on how concomitant medications affect outcomes in mUC patients treated with ICIs.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
文摘Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.
基金supported by the National Natural Science Foundation of China(No.21801153)Natural Science Foundation of Shandong Province(No.ZR2023MB065)+1 种基金Academic promotion program of Shandong First Medical University(No.2019LJ003)High-level Overseas Talent Workstation of Shandong Province.
文摘Green synthesis of drugs is of paramount importance for current public health and a prerequisite to new drugs exploiting.Nowadays,novel strategies of disease diagnosis and therapies are in blooming development as remarkable advances have been achieved which are all highly depended on drug development.Under the current requirements to high production capacity and novel synthesis methods of drugs,green synthesis based on strategies with different ways of empowering,advanced catalysts and unique reaction equipment are attracting huge attention and of great challenging.Higher quality products and environmentally friendly synthesis conditions are becoming more and more important for manufacturing process which has new requirements for catalyst materials and synthesis processes.Polyoxometalates(POMs)are class of transition metals-oxygen clusters with precise molecular structures and superior physicochemical properties which have made longstanding and important applications upon research community of functional materials,catalysis and medicine.In this review,the recent advances of polyoxometalates based strategies for green synthesis of drugs are summarized including POMs based catalysts,alternative reaction equipment based novel synthesis protocols.The significance of POMs to pharmaceutical and industrial field is highlighted and the related perspective for future development are well discussed.
