Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global population.From the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous system.These diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual death.Despite the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining currency.This last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

Recognition and quality mapping of traditional herbal drugs:way forward towards artificial intelligence

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.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Research on Anti-bacterial Effects of 5 Kinds of Chinese Herb Extracts on Ameromonas hydrophila in vitro

[Objective] The aim was to study the anti-bacterial effects of 5 kinds of Chinese herb extracts on Ameromonas hydrophila in vitro. [Method] in vitro anti-bacterial effects of 5 kinds of Chinese herb extracts like Galla Chinensis,Syzygium aromaticum,Salvia miltiorrhiza,Punica granatum L. and Terminalia chebula Retz on Ameromonas hydrophila were studied; furthermore,cure rates of the Chinese herb extracts with better anti-bacterial effects were determined to find out the optimal drug dosage. [Result] Under the same experimental conditions,Galla Chinensis,Punica granatum and Terminalia chebula Retz had relatively strong anti-bacterial effects on Ameromonas hydrophila,among them the anti-bacterial effect of Galla Chinensis was significantly higher than those of the others （P0.05）. The optimal treatment dose of Galla Chinensis treating bacterial septicemia caused by Aeromonas hydrophila was that they were treated with medicated bath for 40 min by 0.5 mg/ml Galla Chinensis extract,and the cure rate was 100%. [Conclusion] The research provides a scientific drug basis for the control and prevention of outbreak bacterial diseases of fish.

Anti-fungal and anti-bacterial activities of ethanol extracts of selected traditional Chinese medicinal herbs

Objective:To evaluate in ritro antimicrobial activities of selected 58 ethno-medicinal plant extracts with a view to assess their therapeutic potential.Methods:A total of 58 traditional Chinese medicinal plants were carefully selected based on the literature review and their traditional use.The antimicrobial activities of ethanol extracts of these medicinal plants were tested against fungi(Aspergillus funigaius),yeast(Candida albicans),gram-negative(Acirelobacter haumannii and Pseudornnruis aeruginosa)and gram-positive bacteria(Staphglococcus aureus).The activities were tested at three different concentrations of 1.00,0.10 and 0.01 mg/mL.The data was analysed using Gene data Screener program.Results:The measured antimicrobial activities indicated that out of the 58 plant extracts,15 extracts showed anti-fungal activity and 23 extracts exhibited anti-bacterial activity.Eight plant extracts have exhibited both anti-bacterial and anti-fungal activities.For instance,Eucommia ulmoides,Pohgonum cuspidcrtum,Poria cocas and Uncaria rhineophylla showed activity against both bacterial and fungal strains,indicating their broad spectrum of activity.Conclusions:The results revealed that the ethanol extracts of 30 plants out of the selected 58 possess significant antimicrobial activities.It is interesting to note that the findings from the current study are consistent with the traditional use.A clear correlation has also been found between the antimicrobial activity and the flavonoid content of the plant extracts which is in agreement with the literature.Hence.the results presented here can be used to guide the selection of potential plant species for the isolation and structure elucidation of novel antimicrobial compounds in order to establish the structure-activity relationship.This in turn is expected to lead the way to the discovery of novel antimicrobial agents for therapeutic use.

Anti-bacterial studies on Hemigraphis colorata(Blume) H.G.Hallier and Elephantopus scaber L.

Objective:To examine the ethanol,aqueous,chloroform,benzene,acetone and petroleum ether extracts of Hemigraphis colorata(H.colorata) leaves and stem and Elephantopus scaber (E.scaber) leaves,root and flower for the presence of phyto-constituents and screened the antibacterial activity against the selected pathogens.Methods:The fresh materials were shade dried and powdered using the tissue blender.The dried and powered materials(50 g) were extracted successively with 200 mL of aqueous,acetone,benzene,chloroform,etganol.and petroleum ether by using Soxhlet extractor for 8 h at a temperature not exceeding the boiling point of the solvent.Aqueous,acetone,benzene,chloroform,ethanol.and petroleum ether extracts were prepared from powdered materials were used for preliminary phytnehemical and antimicrobial studies using standard methods.Results:The crude aqueous,acetone,benzene,chloroform, ethauol.and petroleum ether extracts E.scaber leaves,flower and root and H.colorata leaves and stem demonstrated that out of(5×6×12 = 360) tests for the presence or absence of the above compounds.188 tests gave positive results and the remaining 172 gave negative results. The results of the phvtochemical screening revealed that phenol(12/12).carbohydrates(9/12). steroids(8/12).saponins and coumarins(7/12).tannins(6/12),proteins(5/12).earboxylic acid and flavonoids(4/12).xanthoproteins(3/12) and alkaloids(2/12) presence in the crude aqueous, acetone,benzene,chloroform,ethanol.and petroleum ether extracts of H.colorata leaves and stem.The crude aqueous,acetone,benzene,chloroform,ethanol.and petroleum ether extracts E.scaber leaves,flower and root displayed the presence of phenol(18/18).tannin(17/18). carbohydrates(16/18).steroids(14/18),oarboxylic acid and coumarins(12/18).saponins(10/18), xanthoprotein(9/18).flavonoids(7/18).protein(4/18) and alkaloids(2/18).The root ethanolic extracts of E.scaber illustrated the highest zone of inhibition against three pathogens viz.. Staphylococcus aureus(S.aureus)(24 mm).Escherichia coli(E.coli)(16 mm) and Psemlomonas aeruginosa {P.aeruginosa)(13 mm).The chlorofrom extracts of E.scaber showed the highest zone of inhibition against Bacillus cereus(B.ceretus)(12 mm).The leaves ethanolic extracts of E.scaber demonstrated the highest zone of inhibition against three pathogens viz.,Enterococcus faecalis (E.faecalis)(18 mm).Proteus mirabilis(P.mirabilis)(17 mm).Salmonella Typhi(S.typhi)(14 mm) and Enterobacter sp.(11 mm) While the benzene extracts of H.colorata demonstrated maximum zone of inhibition against the pathogen Acinetobucter sp.(14 mm) and S.aureus (12 mm).Conclusions:It is hoped that this study would direct to the establishment of some compounds that could be used to invent new and more potent antimicrobial drugs of natural origin.

Phytochemical and anti-bacterial activity of epidermal glands extract of Christella parasitica (L.) H. Lev.

Objective:To study the morphology,biochemistry and bioactivity of the epidermal glands of the glandular morphotype of Christella parasitica(C.parasitica)(L.) H.Lev.Methods: Morphological studies on epidermal glands were earned out by using light microscope and scanning electron microscope.To prepare the extract,the shade-dried fronds of glandular morphotype were soaked in acetone.For antibacterial studies paper disc method was followed by using various pathogenic bacteria.Results:Detailed micromorphological,phytochemical and bioactivity studies on a medicinal fern C.parasitica(L.) H.Lev.showed its inlraspecific variation in antibacterial activity.The presence or absence of the epidermal glands was the key factor for antibacterial activity in the morphovariants of this species.The epidermal glands were orange-coloured,stalked and elongated ones of about 84.2μm×45μm,and distributed on the undersurface of cosla,coslules and veins in croziers,young and mature leaves.Frequency of glands varied from 15/cm on costa in mature leaves to 140/cm on costules in croziers.The acetone extract of the glands showed antibacterial activities and also toxic effect against mosquito larvae and tadpoles of frog.Preliminary phytochemical analysis and HPLC studies of the gland extract showed the presence of various kinds of terpenoids,alkaloids,tannins,saponins and flavonoids in it.Conclusions:The present study shows that epidermal glands of the glandular morphotype of C. parasitica(L.) H.Lev.have several bioactive compounds and such rare moiphovariant should be conserved in nature.The next step is to isolate the pure compounds and to screen the bioactivity of individual compounds of the epidermal glands.

Effect of K1, K2 Anti-Bacterial Agents on Tobacco Ralstonia Solanacearum

The tobacco Ralstonia Solanacearum were both cultured on nutrient agar plates and inoculated in seedling stage of tobacco, then treated with K1 and K2, two anti-bacterial agents, at a serial con-centrations to study their inhibitory efficiency. The result indicated that K1 can inhibit R. Solanacearum growth entirely, at the concentration range from 1/50 to 1/5000. K2 can reach the same result at the concentration range from 1/50 to 1/50000. Compared with the control plates, K1, at the concentration 1/50000, had no significant differences, and the average number of colony per plate was 112-115. The immature tobacco shown wilt as soon as inoculated with R. Solanacearum, and recovered gradually after using K1, K2. The densities of microbial suspension, handled by K1, K2 within 10 hs, were both significantly lower than the controlled ones. The optical microscopy also shown that handled microbial body differed from the controlled, whose body was regular short, rod shape as opposed to the handled ones with irregular rod shape and damaged body. All the results indicated that K1 and K2 both had inhibitory effects on tobacco R. Solanacearum, and K2 was more efficient than K1.

In vitro anti-biofilm and anti-bacterial activity of Junceella juncea for its biomedical application

Objective:To investigate the anti-biofilm and anti-bacterial activity of Junceella juncea(J.juncea)against biofilm forming pathogenic strains.Methods:Gorgonians were extraeted with methanol and analysed with fourier transform infrared spectroscopy.Biofilm forming pathogens were identified by Congo red agar supplemented with sucrose.A quantitative spectrophotometric method was used to monitor in vitro biofilm reduction by microtitre plate assay.Anti-bacterial activity of methanolic gorgonian extract(MGE)was carried out by disc diffusion method followed by calculating the percentage of increase with crude methanol(CM).Results:The presence of active functional group was exemplified by FT-IR spectroscopy.Dry,black,crystalline colonies confirm the production of extracellular polymeric substances responsible for biofilm formation in Congo red agar.MGE exhibited potential anti-biofilm activity against all tested bacterial strains.The anti-bacterial activity of methanolic extract was comparably higher in Salmonella typhii followed by Escherichia colt,Vibrio cholerae and Shigella flexneri.The overall percentage of increase was higher by 50.2%to CM.Conclusions:To conclude,anti-biofilm and anti-bacterial efficacy of J.juncea is impressive over biofilm producing pathogens and are good source for novel anti-bacterial compounds.

Design,synthesis and bioevaluation of N-hydroxyquinolinones as potential anti-plasmodial,anti-bacterial and iron(Ⅱ)-chelating agents

OBJECTIVE To establish a small compound library via a versatile synthetic route for the investigation of natural-inspiring compounds containing N-hydroxypyridones motif as potential anti-plasmodial,anti-bacterial and iron(Ⅱ)-chelating agents.METHODS An amidation/cyclization approach was adopted to synthesize a library of N-hydroxyquinolinones.The anti-plasmodial susceptibility of lab clone 3D7 P.falciparum was measured using aprotocol modified from the WHO microtest.The minimum bactericidal concentration(MBC)values were determined against Escherichia coli and Staphylococcus arueus.Nine compounds were selected to test their iron(Ⅱ)-chelating abilities.The iron(Ⅱ)-chelating ability was determined by measuring the absorbance of ferrozine-iron complex at 562 nm.RESULTS A new route for the facile synthesis of a library of N-hydroxyquinolinones based on one-pot palladium catalyzed C-N amidation/dehydrocyclizationsequence was implemented.Four compounds show anti-plasmodial activities with the range of 1.1-1.4μmol·L-1,50% chelation abilities of the nine selected compounds were shown to be 0.24-0.29mmol·L-1.CONCLUSION Alibrary of N-hydroxyquinolinones was synthesized via a novel synthetic route.The anti-plasmodial and anti-bacterial activities of these compounds were evaluated.Four compounds show potent anti-plasmodial activities Nine compounds were examined for their propensities to undergo iron chelation and these compounds were shown to be promising iron(Ⅱ)chelators as compared to EDTA.

Strategies for translating proteomics discoveries into drug discovery for dementia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

Peptide drugs: a new direction in cancer immunotherapy

Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.

Microglia in drug addiction:A perspective from neuroimmunopharmacology

Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.

Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

Biocompatible silver nanoparticles: An investigation into their protein binding efficacies, anti-bacterial effects and cell cytotoxicity studies

Green synthesis of silver nanoparticles(AgNPs)has garnered tremendous interest as conventional methods include the use and production of toxic chemicals,products,by-products and reagents.In this regard,the synthesis of AgNPs using green tea(GT)extract and two of its components,(-)-epigallocatechin gallate(EGCG)and(+)-catechin(Ct)as capping/stabilizing agents,is reported.The synthesized AgNPs showed antibacterial activity against the bacterial strains Staphylococcus aureus and Escherichia coli,along with anticancer activity against HeLa cells.After administering nanoparticles to the body,they come in contact with proteins and results in the formation of a protein corona;hence we studied the interactions of these biocompatible AgNPs with hen egg white lysozyme(HEWL)as a carrier protein.Static quenching mechanism was accountable for the quenching of HEWL fluorescence by the AgNPs.The binding constant(Kb)was found to be higher for EGCG-AgNPs((2.309±0.018)×104 M-1)than for GT-AgNPs and Ct-AgNPs towards HEWL.EGCG-AgNPs increased the polarity near the binding site while Ct-AgNPs caused the opposite effect,but GT-AgNPs had no such observable effects.Circular dichroism studies indicated that the AgNPs had no such appreciable impact on the secondary structure of HEWL.The key findings of this research included the synthesis of AgNPs using GT extract and its constituent polyphenols,and showed significant antibacterial,anticancer and protein-binding properties.The-OH groups of the polyphenols drive the in situ capping/stabilization of the AgNPs during synthesis,which might offer new opportunities having implications for nanomedicine and nanodiagnostics.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.