Mineral oil contaminants composed of saturated hydrocarbons(MOSH)and aromatic hydrocarbons(MOAH)are commonly found in edible oils and related processed foods.Currently,the analysis of mineral oils primarily employs the liquid chromatography-gas chromatography-flame ionization detector(LC-GC-FID)method.Liquid chromatography is used to purify and separate MOSH and MOAH from interfering substances,and the interface technology transfers MOSH or MOAH into different GC channels for quantitative analysis.The MOSH and MOAH chromatograms typically exhibit an irregular hump shape,with sharp peaks above the hump representing natural hydrocarbon interferences,which usually do not affect the identification of the hump profile.However,when the purification of interferences is incomplete,they can form one or more gaps above the hump,interfering with the accurate judgment and delineation of the hump profile,and leading to poor reproducibility of analysis results of mineral oil.In this study,an algorithm that mimicked the manual drawing of the hump shape or contour was proposed for automatically determining the mineral oil hump contour(i.e.,the lower envelope line).The algorithm used a multiple second-order difference quotient filtering method to identify and remove the gaps above the hump.The method involved first searching and determining the lowest value of the mineral oil hump,which was the valley point sequence,and then applying second-order difference quotient filtering to the valley point sequence.Compared to the hump,the second-order difference quotient of sharp peaks was a significantly larger negative value.By filtering out the points in the valley point sequence with larger negative second-order difference quotients(or multiple second-order difference quotients),the sharp peaks above the hump were removed.To verify the accuracy of the algorithm,42 different types of samples,including edible oils and milk powders were analyzed,using both the automatic algorithm and manual methods.The results showed that there were no significant differences in the detected mineral oil contents between these two methods.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To establish dynamic nomogram models for postoperative recurrence and survival risk of patients with AFP-negative hepatocellular carcinoma(ANHC)based on multimodal clinical data,to identify ANHC-specific prognostic biomarker combinations by integrating tumor biological characteristics and treatment response parameters through machine learning,and to provide an individualized risk assessment tool for overcoming the limitations of traditional serum biomarkers.Methods A retrospective analysis was performed for 421 ANHC patients who underwent hepatectomy in Eastern Hepatobiliary Surgery Hospital from April 2012 to December 2018,and they were randomly divided into training group with 210 patients and validation group with 211 patients.The univariate and multivariate Cox proportional-hazards regression models were used to identify independent prognostic factors and establish a nomogram model,and the receiver operating characteristic(ROC)curve,the calibration curve,and the decision curve analysis were used to assess the performance of the model.Related indicators were measured,including prealbumin(PA),white blood cell count(WBC),tumor size,and microvascular invasion.The chi-square test or the Fisher's exact test was used for comparison of categorical variables between two groups,and the independent-samples t test or the Mann-Whitney U test was used for comparison of continuous variables between two groups.Results The multivariate analysis showed that multiple tumors(hazard ratio[HR]=3.30,P<0.001),WBC(HR=1.05,P=0.005),blood glucose(HR=1.15,P=0.026),CA19-9(HR=1.17,P=0.005),and tumor size(HR=1.17,P<0.001)were independent risk factors for disease-free survival(DFS),while PA(HR=0.99,P=0.022)was a protective factor.Incomplete tumor capsule(HR=0.60,P=0.009),age(HR=1.02,P=0.035),prothrombin time(PT)(HR=1.27,P=0.023),CA19-9(HR=1.01,P<0.001),and tumor size(HR=1.15,P<0.001)were independent risk factors for overall survival(OS).The DFS nomogram achieved an AUC of 0.74(95%confidence interval[CI]:0.64-0.84)in the training group and 0.67(95%CI:0.57-0.77)in the validation group,while the OS nomogram had an AUC of 0.76(95%CI:0.64-0.88)and 0.73(95%CI:0.60-0.87),respectively.The calibration curve and the decision curve analysis showed that the models had good predictive accuracy and clinical practicability.Conclusion Preoperative indicators,including tumor number,PA,WBC,and tumor size,can effectively predict postoperative recurrence in ANHC patients,while tumor capsule integrity,age,and PT are significantly associated with OS.The nomogram models established have good performance and can provide a basis for individualized prognostic assessment.

Objective:To construct a framework for evaluating the quality of health economic evaluation methodology based on the pragmatic clinical trial.Methods:An evaluation framework was constructed based on existing quality evaluation tools for health economic evaluation other quality evaluation tools.The weights of each item in the framework were determined by the Delphi method,and the weighted average was calculated using the expert authority coefficient.Results:A total of 23 experts were consulted,and the expert authority coefficients were 0.88 and 0.90,respectively.The results of the Wilcoxon signed-rank test showed no statistically signifi-cant differences among the expert opinions in two rounds(P＞0.05).Finally,a framework with 3 dimensions and 8 items was estab-lished.Conclusion:The evaluation framework has high scientificity and reliability.

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Relevant literature on mobile medical devices combined with the ecological momentary assessment(EMA)method applied to lung cancer patient caring was collected from some databases of CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,CINAHL and Web of Science.The method of scoping review was used to sort out the general characteristics of the included literature,types and application of mobile medical devices,assessment content elements and outcome indicators.The feasibility and validity of mobile medical devices combined with the EMA method for the symptom assessment of lung cancer patients were described,whose advantages in monitoring during lung cancer caring and application prospects were elaborated.The problems of mobile medical devices during practical application were pointed out and some countermeasures were put forward accordingly.References were provided for personalized remote caring of lung cancer patients and development of intelligent multi-modal mobile devices.[Chinese Medical Equipment Journal,2025,46(10):71-77]

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.