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.

Objective To provide a scientific basis for vector prevention and control in port areas, vector monitoring has been conducted continuously to characterize the composition, density, and seasonal fluctuations of vectors across 21 port-areas of Shandong province from 2017 to 2023. Methods In accordance with the Regional Vector Monitoring Plan for Frontier Ports, vector surveillance of mosquitoes, flies, cockroaches, rodents, and other disease vectors was performed. Data were analyzed to describe vector community composition and identify seasonal fluctuations. Results A total of 601 rodents belonging to 1 family, 4 genera, and 4 species were captured. Three dominant rodent species inhabit port areas. In addition, 88 104 mosquitoes were captured and classified into 3 subfamilies, 4 genera, and 12 species; 38 959 flies were trapped and classified into 8 families,31 genera, and 51 species, including 9 dominant fly species in port-areas; and 54 672 captured cockroaches were classified into 2 families,4 genera, and 4 species, with Blattella germanica as the dominant species. Conclusions Significant vector community changes(P＜0.005)have been identified after the epidemic. To improve the pertinence and efficacy of port health quarantine work, continuous and strong attention should be paid to vector compositions and population densities at Shandong ports.

Objective: To study the effects and potential mechanisms of the aquaporin 1(AQP1) inhibitor acetazolamide(AZ) on the proliferation, apoptosis, and inflammatory response of rheumatoid arthritis(RA) fibroblast-like synoviocytes(FLS). Methods: TNF-α-induced RA-FLS was served as in vitro RA model. MTT assay, IF staining, and EdU incorporation assay were applied to study AZ′s effects on RA-FLS proliferation. Hoechst staining, flow cytometry analysis of Annexin V-FITC/PI-stained cells, and mitochondrial membrane potential detection experiments were used to detect cell apoptosis. ELISA and quantitative real-time PCR methods were used to measure pro-inflammatory cytokine production. Cell autophagy was evaluated using IF staining and mCherry-GFP-LC3B puncta assay. Western blot was performed to detect the levels of autophagy, apoptosis, and proliferation-related proteins. Moreover, the role of autophagy inhibition in AZ′s effects on RA-FLS was examined by co-treating with the autophagy activator rapamycin(RAPA) or the autophagy inhibitor 3-methyladenine(3-MA). Results: AZ dose⁃dependently inhibited cell proliferation , promoted apoptosis , and reduced the production of pro⁃inflammatory cytokines in RA⁃FLS. Furthermore , AZ suppressed cytoprotective autophagy in these cells , as evidenced by decreased LC3B levels ( P < 0. 05 ) , increased p62 expression ( P < 0. 05 ) , and reduced autophagic flux ( P <0. 01) . Particularly , AZ ′s beneficial effects were reversed by RAPA⁃induced autophagy activation and enhanced by 3 ⁃MA⁃induced autophagy inhibition. Conclusion This study provides the first evidence that AZ hinders cytoprotective autophagy , thereby alleviating the hyperproliferation , apoptosis resistance , and aberrant inflammatory response of RA⁃FLS , revealing the core role of autophagy inhibition in AZ ′s anti⁃RA effects.

By using a strategy of leveraging the ability of metal-organic frameworks(MOFs)materials to precisely regulate the spatial orientation of cyclodextrins(CD),a polystyrene-modified γ-cyclodextrin metal-organic frameworks(PS-CD-MOFs)capillary coating was established and applied to the chiral separation of amino acids in open-tubular capillary electrochromatography(OT-CEC)based on the excellent film-forming property of polystyrene(PS).Characterization results by Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD)indicated that PS was successfully grafted onto the surface of CD-MOFs.The modification significantly improved the structural stability and thermal stability of CD-MOFs while maintaining the integrity of the MOFs.The PS-CD-MOFs coated capillary electrophoresis system exhibited excellent performance in separating dansylated amino acid enantiomers(Dns-D,L-AAs).Specifically,under the optimal separation conditions(Sodium dodecyl sulfate/boric acid buffer system,20 cm capillary,and 10 kV effective voltage),good separation was achieved for D,L-methionine(D,L-Met)and D,L-serine(D,L-Ser).Further quantitative analysis showed that Dns-D,L-Met presented a good linear relationship in the concentration range of 10.0-1500.0 μmol/L,with a correlation coefficient close to 0.998,demonstrating high sensitivity and repeatability.Not only did it overcome the problem that traditional CD(used as additives in capillary electrophoresis)could not precisely control the spatial orientation of chiral resolvents,but also it solved the issues of insufficient stability and bonding amount of CD-MOFs coatings by utilizing the excellent film-forming property of polymers on the inner wall of capillaries.This study provided an efficient and controllable new strategy for construction of chiral separation stationary phases.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Objective:To investigate the awareness levels of doctors from various departments regarding fertility preservation to provide reference and suggestions for further improving awareness and promoting multidisciplinary development in fertility preservation.Methods:From November to December 2023, the China Alliance of Fertility Preservation initiated this survey covering 88 hospitals in 23 cities across 20 provinces in China. The survey focused on the degree of understanding of basic concepts, technological perceptions, treatment concepts, and related challenges regarding fertility preservation. Descriptive statistics and Fisher's exact test were used to analyze the difference in awareness levels across various departments.Results:There was a significant difference in the awareness of fertility preservation guidelines among physicians from different departments ( P<0.001). Reproductive center physicians had the highest level of understanding [68.3% (41/60)]. Doctors in the reproductive centers had a higher awareness rate of the five fertility preservation techniques (ovarian tissue cryopreservation, oocyte cryopreservation, sperm cryopreservation, testicular tissue cryopreservation, and embryo cryopreservation) than that in other departments (all P<0.05). Regarding treatment concepts, more reproductive center physicians believed that psychological counselling about fertility preservation before oncological treatment was necessary ( P=0.016). Hematologists had more worries and concerns about fertility preservation treatment. Additionally, 96.7% (58/60) of reproductive center physicians expressed the need to establish effective referral mechanisms within the same city, province, or across provinces. However, 55.6% (35/63) of oncologists, 64.6% (31/48) of hematologists, and 77.8% (7/9) of pediatricians considered treating primary tumors far more important than fertility preservation. Conclusion:Doctors from different departments have varying levels of understanding regarding fertility preservation. It is necessary to strengthen the dissemination and training of fertility preservation knowledge among physicians from various departments, as well as to promote a multidisciplinary treatment model to improve efficiency, to establish a comprehensive referral mechanism to improve patients' opportunities for fertility preservation.

Purpose To investigate the role of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the diagnosis of breast cancer.Methods Fine needle aspiration cytology(FNAC)samples of 203 patients with breast cancer were selected and prepared by liquid-based cytology.The results of histopathology after neoadjuvant therapy were used as the gold standard to compare with the diagnostic results of FNAC samples,and then evaluated the diagnos-tic coincidence rate of FNAC samples.Results Of 203 axillary lymph node FNAC samples,111 cases were diagnosed as positive,38 cases were diagnosed as suspicious for positivity,and 54 cases were diagnosed as negative.The diag-nostic accuracy of FNAC was 85.2％,the sensitivity of FNAC was 98.0％,and the specificity of FNAC was 90.0％.Conclusion FNAC has high sensitivity and accuracy in the diagnosis of axillary lymph node metastasis.Sentinel lymph node biopsy is recommended for patients with negative FNAC but clinically and radiographically suspected lymph node metastasis.

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.