OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Yttrium-90 selective internal radiation therapy (⁹⁰Y-SIRT) is a treatment technique that delivers radioactive microspheres precisely to the arterial vascular bed of neoplasms, utilizing beta radiation to administer a high local dose of radiation to the neoplasm tissues. This technology has demonstrated significant efficacy in patients with unresectable pirmary liver cancers and liver metastases. This article systematically reviews the development history and clinical application status of ⁹⁰Y-SIRT in the treatment of liver cancer, and looks forward to future development directions.

AIM To study the chemical constituents from Inula japonica Thunb.and their anti-asthmatic activity.METHODS Separation and purification were performed using silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The effect of compounds on the release rate of β-Hex was evaluated by substrate coloration method.RESULTS Twenty-three compounds were isolated and identified as dehydrodontic acid(1),vitexin(2),alternariol(3),globuxanthone(4),1,3,6,7-tetrahydroxyxanthone(5),hydroxyhydrolapachol(6),isoscopoletin(7),elephanmollen(8),benzoylcholine(9),hoconobiflavone(10),clovandiol(11),hydroxydihydrobovolide(12),5,7-dihydroxycoumarin(13),scopoletin(14),orlichenol glucoside(15),urolignoside(16),9-angeloyloxythymol(17),6,3′,4′-trihydroxyaurone(18),flufuran(19),sweroside(20),guajadial(21),5,7,4′-trimethoxy-4-phenylcoumarin(22),dibutylphthalate(23).After intervention with compounds 9 and 16,the release rates of β-Hex were(56.64±2.37)％and(58.07±2.29)％,respectively.CONCLUSION Compounds 1-23 are isolated from Ⅰ.japonica for the first time.Compounds 9 and 16 have anti-asthmatic activity.

Objective:To investigate the risk factors influencing mortality in neonates undergoing continuous renal replacement therapy (CRRT).Methods:This retrospective study included 34 neonates with a corrected age of≤28 days who received CRRT at the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, from January 2019 to December 2023. The neonates were divided into a mortality group ( n=16) and a survival group ( n=18) based on whether they died during CRRT. Pre-CRRT blood biochemical indices, general condition, CRRT treatment modes, parameters, and related complications were analyzed using t-tests, Wilcoxon signed-rank tests, and Chi-square tests. Logistic stepwise regression analysis was used to screen for risk factors associated with CRRT mortality. Results:The mortality rate among the 34 neonates was 48.6% (16/34), with a median CRRT age of 17 days (range: 2-33 days). Eleven neonates (32.3%) were preterm, with the youngest gestational age being 27 weeks and the lowest weight before CRRT initiation being 1 700 g. The mortality group had lower urine output 6-12 hours before CRRT initiation and lower critical illness scores compared to the survival group [0.05 (0.02-1.00) ml/(kg·h) vs. 0.50 (0.20-1.05) ml/(kg·h), (64.50±7.10) scores vs. (77.67±3.65) scores, Z or t values were 10.97 and 3.91, respectively]. However, the vasoactive inotropic score (VIS), proportion of coma, and levels of blood potassium, alanine aminotransferase, aspartate aminotransferase, blood ammonia, blood lactic acid, and activated partial thromboplastin time (APTT) were higher in the mortality group compared to the survival group [ (86.88±15.80) scores vs. (55.56±24.31) scores, 11/16 vs. 1/18, (7.02±1.73) mmol/L vs. (5.88±1.53) mmol/L, 274.55(132.50-664.98) U/L vs. 31.10(19.03-110.70) U/L, 688.20 (449.73-3 618.13) U/L vs. 96.65 (44.15-439.00) U/L, 232.75 (70.33-1 310.85) μmol/L vs.77.70 (49.78-919.05) μmol/L, (11.17±3.36) U/L vs. (7.99±2.67) U/L, and (99.57±39.74) s vs. (60.97±31.25) s, with t, χ2, or Z values of－4.39, 14.81,－2.03,－2.72,－11.81,－3.89,－3.06, and－3.17, respectively] (all P<0.05). Logistic regression analysis revealed that pre-treatment VIS value ( OR=1.150, 95% CI: 1.035-1.278), and blood ammonia level ( OR=1.004, 95% CI: 1.002-1.009) were independent risk factors for mortality (both P<0.05). Conclusions:Neonatal CRRT mortality is associated with pre-treatment VIS scores and blood ammonia levels. Attention should be paid to a rapid decreases in urine output, the intensity of vasopressor support, and elevated levels of blood ammonia, blood lactic acid, transaminases, and APTT at the initiation of treatment.

AIM To investigate the clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung.METHODS One hundred and fifty-six patients were randomly assigned into control group(78 cases)for 7-day administration of azithromycin,and observation group(78 cases)for 7-day administration of both Yifei Tongluo Decoction and azithromycin.The changes in clinical effects,disappearance time of local symptoms,mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,pulmonary function indices(PEF,VPTEF,MMF,TPTEF),inflammatory factors(sB7-H3,Cgp-39,sICAM-1,CCL5),immune function indices(RBC-C3bR,RBC-ICR,CD3+,CD4+)and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05),along with shorter disappearance time of local symptoms(P＜0.05).After the treatment,the two groups displayed decreased mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,inflammatory factors,RBC-ICR(P＜0.05),and increased pulmonary function indices,RBC-C3bR,CD3+,CD4+(P＜0.05),especially for the observation group(P＜0.05).No obvious difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung,Yifei Tongluo Decoction combined with azithromycin can safely and effectively alleviate clinical symptoms,improve pulmonary functions,and reduce body inflammatory responses.

Objective Magnetic resonance angiography(MRA)offers a non-invasive and radiation-free advantage in detecting and diagnosing intracranial artery stenosis;however,it is associated with high equipment costs.Transcranial color-coded Duplex ultrasound(TCCD)combined with contrast-enhanced ultrasound(CEUS)presents advantages such as non-invasiveness,real-time dynamic monitoring,and low cost.Nevertheless,there were no reports comparing the sensitivity,specificity,diagnostic agreement with MRA,or health economic evaluation of TCCD combined with CEUS for detecting major intracranial artery stenosis.Methods From April 2023 to August 2024,a total of 55 patients suspected of having intracranial artery stenosis or occlusion were recruited at Beijing Tiantan Hospital,Capital Medical University.Both TCCD combined with CEUS and MRA were performed to evaluate the degree of stenosis in the terminal segment of the internal carotid artery,M1 and M2 segments of the middle cerebral artery,A1 and A2 segments of the anterior cerebral artery,P1 and P2 segments of the posterior cerebral artery,and the V4 segment of the vertebral artery.Intracranial artery stenosis was categorized into three groups:normal/mild,moderate,and severe/occlusion.Sensitivity,specificity,and consistency between the two methods were calculated.The Wilcoxon signed-rank test was used to compare the differences in examination costs and diagnostic time.Results Fifty-five high-risk patients(110 cerebral hemispheres in total)with suspected cerebrovascular stenosis were included(median age:46 years;69.0%male).TCCD combined with CEUS and MRA were performed simultaneously.TCCD combined with CEUS showed high sensitivity and specificity in diagnosing intracranial artery stenosis,with good consistency compared to MRA.The highest diagnostic consistency was observed in the M2 segment(Kappa=0.704)and A2 segment(Kappa=0.650),while the M1 segment showed moderate consistency(Kappa=0.569).The average cost of TCCD combined with CEUS was 240 CNY with a diagnostic duration of 21 min,compared to 722 CNY and 287 min for MRA(P<0.001,effect sizer=0.89-0.91).Conclusion Compared to MRA,TCCD combined with CEUS demonstrates higher consistency in screening for stenosis in the M2 segment of the middle cerebral artery and the A2 segment of the anterior cerebral artery.It is also more cost-effective.However,MRA has advantages in assessing deep intracranial vessels.A synergistic use of both methods can optimize the allocation of diagnostic resources for intracranial artery stenosis.It is recommended that primary healthcare institutions adopt TCCD as the initial screening tool,and,with standardized training and technical upgrades,combine it with CEUS.Complex cases should be referred for detailed evaluation by using MRA.

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.