The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

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

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

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*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To compare the interaction efficiency of three human-machine interaction modes with hand-touch control,eye movement control and voice control,based on a multi-channel human-machine interaction system in flight mission scenarios.Methods 20 pilots took part in the study and completed the first level(relatively simple)and second level(relatively complex)interactive experimental tasks in three human-computer interaction modes based on specific flight mission scenarios.The interaction efficiency indicators included the system's interaction time,response time,fusion calculation time,and number of errors.After the experiment was completed,the pilots conducted a subjective evaluation,which included the suitability of the interaction mode to the task,consistency with expected usage,fault-tolerance,effective feedback,and the tendency of the interaction mode to be applied in future flight fields.Results There were generally significant differences in interaction efficiency between hand-touch control,voice control,and eye movement control in flight mission scenarios,but the differences differed in first-level and second-level interaction tasks.Based on the comprehensive interaction experimental tasks at all levels,the experimental results obtained included:(1)the interaction time of hand-touch control was the shortest,the interaction time of voice control was the longest,and the main effect of the interaction mode was significant(F=18.214,P<0.001,η2=0.565);(2)The response time of hand-touch control was the shortest,while the response time of eye movement control was the longest.The main effect of interaction mode was significant(F=153.085,P<0.001,η2=0.944);(3)The fusion calculation time for hand-touch control was the shortest,while the fusion calculation time for voice control was the longest.The main effect of the interaction mode was significant(F=41.702,P<0.001,η2=0.777);(4)The errors in voice control were the least,while those in eye movement control were the most.The main effect of interaction mode was significant(χ2=22.845,P<0.001,φ=1.097);(5)The subjective evaluation scores of pilots on voice control were higher than those on eye movement control,and all had statistical significance(P<0.001,P<0.01).Conclusions This study focuses on flight interaction tasks and compares the interaction efficiency of three interaction modes of hand-touch control,voice control,and eye movement control,through a combination of experiments and subjective evaluations.The differences in various interaction efficiency indicators among different interaction modes are found,and the interaction modes have a significant impact on interaction efficiency.Hand-touch control has a significant advantage in interaction time efficiency,voice control has an advantage in accuracy for simple tasks,while eye movement control has relatively weak time efficiency and accuracy;Compared to eye movement control,pilots exhibit higher evaluations and tendencies towards voice control.The research results can provide reference for the future design,evaluation,and application of multi-modal interaction systems.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

Objective To explore the correlations between triglyceride glucose index(TyG)and its derivatives TyG-body mass index(BMI)and TyG-alanine transaminase(ALT)with the risk of lean metabolic associated fatty liver disease(MAFLD).Methods A total of 207 patients diagnosed with lean MAFLD and 100 lean healthy controls who received annual health examination in Health Management Center of our hospital from Jul.to Dec.2023 were enrolled.Plasma lipids,blood glucose,liver function,TyG,TyG-BMI and TyG-ALT were compared between the 2 groups.The influencing factors of lean MAFLD were analyzed by univariate and multivariate logistic regression models.All subjects were divided into 4 subgroups(Q1-Q4)according to the quartile of TyG and its derivatives,and the prevalence of lean MAFLD in each subgroup was observed.The receiver operating characteristic(ROC)curves of TyG,TyG-BMI and TyG-ALT for lean MAFLD were plotted to evaluate the prediction efficiency.Results Of the 8 764 health examination cases included,2 350(26.8％)had MAFLD,of which 207 were lean MAFLD(8.8％,207/2 350).Compared with the lean healthy controls,the patients in the lean MAFLD group were older,with more male and high BMI,and their fasting blood glucose,total cholesterol,triglyceride,low density lipoprotein-cholesterol,ALT,aspartate transaminase,γ-glutamyl transpeptidase,alkaline phosphatase,total bilirubin,TyG,TyG-BMI and TyG-ALT were significantly increased,while high density lipoprotein-cholesterol was significantly decreased(all P＜0.01).Logistic regression analysis showed that age,male,and elevated ALT level were independent risk factors for lean MAFLD.The prevalence of lean MAFLD in the Q4 subgroup of TyG was significantly higher than that in the Q1 and Q2 subgroups(34.3％[71/207]vs 10.6％[22/207]and 24.2％[50/207],both P＜0.05).The prevalence rates of lean MAFLD in the Q4 subgroup of TyG-BMI and the Q4 subgroup of TyG-ALT were significantly higher than those in the corresponding Q1,Q2,and Q3 subgroups(35.3％[73/207]vs 8.2％[17/207],24.6％[51/207],and 31.9％[66/207];33.8％[70/207]vs 14.0％[29/207],23.2％[48/207],and 29.0％[60/207];all P＜0.05).The area under curve(AUC)of TyG-BMI in predicting lean MAFLD was 0.869 0(95％confidence interval[CI]0.825 5-0.912 6,P＜0.001),which was higher than that of TyG(AUC=0.818 8[95％CI 0.768 0-0.869 6,P＜0.001])and TyG-ALT(AUC=0.772 5[95％CI 0.718 7-0.826 2,P＜0.001]).Conclusion TyG,TyG-BMI,and TyG-ALT are associated with lean MAFLD,and have predictive value for lean MAFLD.TyG and its derivatives are easy to calculate and cheap,and can be used for preliminary clinical assessment of lean MAFLD.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.