BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Traditional Chinese medicine formula (TCMF) represents a fundamental component of Chinese medical practice, incorporating medical knowledge and practices from both Han Chinese and various ethnic minorities, while providing comprehensive insights into health and disease. The foundation of TCMF lies in its holistic approach, manifested through herbal compatibility theory, which has emerged from extensive clinical experience and evolved into a highly refined knowledge system. Within this framework, Chinese herbal medicines exhibit intricated characteristics, including multi-component interactions, diverse target sites, and varied biological pathways. These complexities pose significant challenges for understanding their molecular mechanisms. Contemporary advances in artificial intelligence (AI) are reshaping research in traditional Chinese medicine (TCM), offering immense potential to transform our understanding of the molecular mechanisms underlying TCMFs. This review explores the application of AI in uncovering these mechanisms, highlighting its role in compound absorption, distribution, metabolism, and excretion (ADME) prediction, molecular target identification, compound and target synergy recognition, pharmacological mechanisms exploration, and herbal formula optimization. Furthermore, the review discusses the challenges and opportunities in AI-assisted research on TCMF molecular mechanisms, promoting the modernization and globalization of TCM.
Artificial Intelligence ; Drugs, Chinese Herbal/pharmacokinetics* ; Humans ; Medicine, Chinese Traditional ; Animals

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*

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

BackgroundNon-suicidal self-injury （NSSI） represents a prevalent clinical feature among adolescent patients with major depressive disorder. Existing research has suggested that interoceptive awareness might be linked to NSSI behaviors， but investigations into this association among adolescent patients with major depressive disorders remain limited. ObjectiveTo elucidate the correlation between NSSI behaviors and interoceptive awareness in adolescent patients with major depressive disorder， and to identify influencing factors of NSSI behaviors， in order to provide clinical prevention and treatment strategies. MethodsA total of 125 adolescent patients who met the diagnostic criteria for major depressive disorder as outlined in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the Fourth People's Hospital of Hefei from December 2022 to June 2024. These participants were subsequentially categorized into NSSI behavior group （n=60） and non-NSSI behavior group （n=65） based on the presence or absence of NSSI behaviors. Additionally， a control group comprising 40 healthy adolescents was concurrently assembled for comparison. The Hamilton Depression Scale-17 item （HAMD-17） was used to assess the depressive symptoms of adolescent patients with major depressive disorder， and the Multidimensional Assessment of Interoceptive Awareness version 2- Chinese （MAIA-2） was used to evaluate the interoceptive awareness level of all subjects. Pearson correlation analysis was employed to examine the correlation between HAMD-17 scores and MAIA-2 scores. Binary Logistic regression analysis was conducted to identify the influencing factors of NSSI behaviors in adolescent patients. Then the receiver operating characteristic （ROC） curve was drawn to verify the predictive efficacy of MAIA-2 scores for NSSI behaviors in adolescent patients with major depressive disorder. ResultsSignificant differences were identified across six MAIA-2 subscales （noticing， not distracting， not worrying， attention regulation， emotional awareness， body listening） and the MAIA-2 total score among the three groups （F=18.475， 20.631， 6.044， 5.621， 18.456， 12.889， 12.741， P<0.01）. Correlation analysis underscored a notable negative correlation between the MAIA-2 total score and the HAMD-17 total score， as well as its scores on subscales pertaining to weight and cognitive impairment factors（r=-0.315， -0.203， -0.278， P<0.05）. Binary Logistic regression results indicated that longer disease duration （OR=1.112， 95% CI： 1.043–1.206） and higher HAMD-17 total score （OR=2.071， 95% CI： 1.361–3.150） were risk factors for NSSI behavior in adolescents with depressive disorder， while a higher MAIA-2 total score was a protective factor against NSSI behavior in this population （OR=0.580， 95% CI： 0.407–0.828）. The MAIA-2 total score demonstrated a relatively high predictive value for NSSI behaviors in adolescent patients with major depressive disorder （AUC=0.793）. ConclusionNSSI behaviors in adolescent patients with major depressive disorder are closely related to the disease course， severity of depression， and specific interoceptive awareness patterns. Moreover， interoceptive awareness may serve as a predictive indicator for the occurrence of their NSSI behaviors. ［Funded by the National Key Clinical Specialty Construction Project of China； Anhui Provincial Clinical Key Specialty Construction Project； the Hospital-Level Scientific Research Project of the Fourth People's Hospital of Hefei （number， HFSY2022YB07）］

Objective: To explore the relationship between psychological resilience and attention bias towards negative information in secondary vocational school students, so as to provide reference for developing their mental health work. Methods: In May, 2024, 177 secondary vocational students were selected from the technical secondary vocational school by convenient sampling method. The experiment utilized a mixed experimental design of 2 (group: high psychological resilience group, low psychological resilience group) ×2 (type of stimulus: negative stimulus, neutral stimulus). Adolescents were divided into the high psychological resilience group ( n =32) and the low psychological resilience group ( n =31) based on their scores from the Adolescent Psychological Resilience Scale. Both groups completed the classical dot probing task, with correct rate, reaction time serving and attention biasvalues as primary indicators to assess attention bias. Repeated measures ANOVA was used to compare the reaction time and accuracy of attention bias tasks between two groups of participants, and Pearson correlation analysis was performed on the five dimensions of psychological resilience and attention bias values. Results: The low resilience group exhibited significantly faster response time to negative stimuli compared to neutral stimuli [(579.11±85.44, 586.13±78.92)ms, F (1,61)=5.93, P <0.05]. Additionally, the accuracy of responses to negative stimuli in the low resilience group was significantly lower than that of neutral stimuli [(0.93±0.12, 0.95±0.09), F (1,61)=12.81, P <0.01]. Attention bias values were significantly higher in the low resilience group (7.03±18.43) compared to the high resilience group (-2.54±13.39) ( t =2.36, P <0.05). Pearson correlation analysis revealed a marginally significant negative correlation between the interpersonal assistance (2.85±0.77) and attention bias values (2.20±16.65) ( r=-0.25, P <0.05). Conclusion Secondary vocational school students with low psychological resilience showed a significant attention bias towards negative emotional stimuli, which may render them more susceptible to such stimuli.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To evaluate an ultrasound-based deep learning radiomics nomogram(DLR_Nomo-gram)for non-invasively differentiating between type Ⅰ and type Ⅱ epithelial ovarian cancer(EOC)before surgery.Methods In this study,a cohort of 195 patients diagnosed with EOC was analyzed.Participants were randomly divided into a training set and a testing set at an 8∶2 ratio.Following data preprocessing,region of interest(ROI)delineation,feature extraction and selection,as well as the clipping and extraction of the maximum section sonogram for each sample,three initial models were developed:the radiomics signature(Rad_Sig),the deep transfer learning signature(DTL_Sig),and the clinical signature(Clinic_Sig).Subsequently,an integrated model—referred to as the DLR_Nomogram—was constructed by combining Rad_Sig,DTL_Sig,and Clinic_Sig,and was presented in the form of a nomogram.The performance of the model was evaluated using the receiver operating characteristic(ROC)curve and the corresponding area under the curve(AUC).Results In the testing set,the DLR_Nomogram demonstrated superior predictive performance(AUC:0.951,95%CI:0.876～1.000)compared to Rad_Sig(AUC:0.709,95%CI:0.539～0.880),DTL_Sig(AUC:0.842,95%CI:0.712～0.972),and Clinic_Sig(AUC:0.916,95%CI:0.827～1.000).The Hosmer-Lemeshow goodness-of-fit test for the DLR_Nomogram resulted in a p-value exceeding 0.05,indicating adequate model calibration.Moreover,decision curve analysis revealed that the DLR_No-mogram offers a higher net clinical benefit across a defined range of threshold probabilities.Conclusions The ultrasound-based DLR_Nomogram exhibits a robust ability to differentiate between Type Ⅰ and Type Ⅱ EOC,and may serve as a valuable clinical tool for guiding individualized preoperative diagnostic and therapeutic decision-making.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.