Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

A young female patient with acne and elevated testosterone level underwent plasma steroid hormones testing and found a significant increase in aldosterone. We excluded testing interference and verified the absence of hypertension, hypokalemia, and adrenal occupancy, as well as primary and secondary hyperaldosteronism. During follow-up, a temporal correlation was found between aldosterone levels and the use of drospirenone and ethinylestradiol tablets. It was observed that the combination of drospirenone and ethinylestradiol could lead to the increase of aldosterone level and the concentration ratio of aldosterone to direct renin through different mechanisms. Drospirenone exerts an antagonistic effect on mineralocorticoid receptor to prevent the development of hypertension or hypokalemia. In clinical practice, it is necessary to pay attention to the effect of this drug on screening markers for primary aldosteronism. In the laboratory examination, when female patients with no symptoms of hypertension and hypokalemia but with elevated aldosterone levels are encountered, it can be verified whether they have a history of use of compound estrogen-progestin such as drospirenone and ethinylestradiol tablets, and appropriate tips are provided in the report.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ² test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Liver Neoplasms/pathology* ; Retrospective Studies ; Infusions, Intra-Arterial ; Treatment Outcome

Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.

Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.

Objectives: To examine the impact of probiotics on the lung development of preterm birth of Bama pig. Methods: From April 2020 to October 2021, this animal experimental research was performed by setting up preterm (birth at gestation 104 d), full-term (birth at gestation 113 d), preterm with probiotics (birth at gestation 104 d treated with probiotics given at 3 d after birth), and full-term with probiotics (birth at gestation 113 d treated with probiotics given at 3 d after birth) groups and using the preterm Bama minipig model, the body weights were recorded and lung, ileum, and intestinal content samples were collected at birth, 4 days, 9 days, and 21 days after births of the piglets in preterm and full-term groups, the same samples were collected on 9 days after births of the piglets in preterm with probiotics and full-term with probiotics groups. The body weight and radial alveolar counts (RAC) were compared to evaluate the lung development of the piglets. The lengths of ileal villus were compared to evaluate the development of ileum. The composition structures of bacteria in ileum were analyzed by 16 S rRNA sequencing. The statistical analyses between different groups were performed by t test. Results: There were totally 30 piglets (16 female piglets and 14 male piglets) involving 12 piglets in preterm and full-term groups respectively and 3 piglets in preterm with probiotics and full-term with probiotics groups respectively. The body weights of the piglets in preterm group were lower than those in full-term group at 4, 9 and 21 d after birth ((507±27) vs. (694±56) g, (620±35) vs. (1 092±154) g, (1 660±210) vs. (2 960±418) g,t=2.96, 2.99, 2.78, all P<0.05). The alveolarization of the preterm piglets at 9 days after birth was significantly lower than that of the full-term piglets at the equivalent time point (4.00±0.29 vs. 6.11±0.35, t=4.64, P<0.01). The bacteria genus with the highest abundance in ileum were all different between the preterm and the full-term groups at 4, 9 and 21 d after birth (4 d Escherichia-Shigella (26.63%) and Enterococcus (30.48%) respectively;9 d Turicibacter (35.94%) and Lactobacillus (27.33%) respectively;21 d Escherichia-Shigella (28.02%) and Lactobacillus (46.29%) respectively). The heights of ileal villus of the preterm piglets at 9 d after birth were significantly lower than those of the full-term minipigs at the equivalent time point ((297±21) vs. (411±32) μm, t=3.01, P=0.007).There were both no differences in the body weight and alveolarization ((692±36) vs. (767±67) g, 5.44±0.34 vs. 5.89±0.26, t=0.74, 1.04, both P>0.05) between the piglets in preterm with probiotics group and those in full-term with probiotics group. Turicibacter was the dominant genus in the piglets of both preterm with probiotics and the full-term with probiotics groups. The heights of ileal villus of the piglets in preterm with probiotics group were significantly longer that those of the piglets in preterm group ((371±13) vs. (297±21) μm, t=3.04, P=0.006), and were both not significantly different from those of the piglets in full-term with probiotics group and full-term group ((371±13) vs. (338±12) and (411±32) μm, t=1.90, 1.15, both P>0.05). Conclusions: Premature birth could impact the lung alveolarization of piglets. The probiotics could improve the lung alveolarization of preterm minipigs by promoting the development of ileum.
Animals ; Body Weight ; Female ; Humans ; Lung ; Male ; Pregnancy ; Premature Birth ; Probiotics/therapeutic use* ; Swine ; Swine, Miniature

Aim To reveal the aetion mechanism of Trillium tschonoskii Maxim (TTM) in the treatment of myoeardial ischemia ( MI) by using network pharma¬cology combined with molecular docking.Methods Compounds of TTM were detected and fished out from TCMID, TCM@TAIWAN , BATMAN-TCM database, and the literature data from PubMed , CNK1, and WAN- FANGD database.PharmMapper database was used to find the targets related to compounds, and DISGeNET, GeneCards, DrugBank and OMIM databases were used to find the targets related to Ml.The predictive targets of TTM in the treatment of Ml were obtained.Cytosca- ope 3.1.2 Software and String database were used to build compound-target network and PP1 network.Gene ontology ( GO ) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathway enrichment analysis were performed by utili¬zing the CludterProfiler Software package of RStudio software.The molecular docking was used for verifying the results of network analysis.Results The 10 active compounds of TTM were screened , and 13 core targets of Ml were predicted, such as ALB, EGFR, MAPK1 , CASP3,ESR1 ,etc.A total of 28 Ml-related signaling pathways were fished out.The results of molecular docking showed that the core active ingredients had good binding activity with the key targets.Conclusion TTM may play a role in the treatment of Ml through regulating multiple ingredients, multiple pathways, and multiple targets.