OBJECTIVE To systematically review the current application of discrete choice experiment （DCE） in the value assessment and preference measurement of orphan medicinal product （OMP）， and to provide a reference for the standardized use of this methodology in China. METHODS The systematic search was conducted across Chinese and English databases including CNKI， Wanfang Data， VIP， CBM， PubMed， Web of Science， Medline， and Embase. Original studies that employed DCE to evaluate the value or preferences related to OMP were included. The methodological quality and reporting completeness of the included studies were assessed using the ISPOR Conjoint Analysis Checklist and the DIRECT Checklist， respectively. Respondent populations， attribute setting， and the relative importance of attributes were summarized and analyzed. RESULTS Eight eligible studies were included； all studies demonstrated high-quality reporting and methodological rigor. Respondents comprised the general public， patients/caregivers， policymakers， and other stakeholders. The number of DCE attributes ranged from 4 to 13 （median＝7.5）. Through thematic synthesis， these attributes were categorized into three dimensions， namely “disease-related” “treatment-related” and “economic/financial-related” along with 14 secondary criteria. The most frequently included secondary criteria were treatment efficacy （13 occurrences）， disease severity （9 occurrences）， safety （7 occurrences）， unmet medical need （6 occurrences）， and treatment cost （5 occurrences）. Rankings of relative importance identified treatment efficacy as the most valued criterion across most studies， followed by health insurance financing. CONCLUSIONS DCE applications in the value assessment of OMP have begun to converge on a relatively consistent core attribute framework and selection preference. Future research should further promote the use of DCE to inform attribute and criterion selection in multi-criteria decision analysis frameworks for OMP.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.

Objective:To construct a risk warning model for severe mycoplasma pneumoniae pneumonia(SMPP)children based on clinical data,laboratory indicators and imaging indicators.Methods:162 Mycoplasma pneumoniae pneumonia(MPP)children who were admitted in Foshan Women and Children Hospital from January 2021 to December 2023 were selected,64 SMPP children were included in severe group,the remaining 98 children were included in mild group.The general data,laboratory indicators and imaging indicators of the children were collected.The influencing factors for the occurrence of SMPP were analyzed by univariate and multivariate logistic regression models,and a risk warning model for the occurrence of SMPP children was constructed based on multivariate logistic regression model.The predictive value of the risk warning model for the occurrence of SMPP were analyzed by receiver operating characteristic(ROC)curve.Results:The proportion of 3 years old ≤ age＜6 years old,course of disease,body temperature,fever course,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),lactate dehydrogenase(LDH),cyanosis of lips,positive triconcave sign,pleural effusion,lesion site was the lower lobe,abnormal electrocardiogram and extrapulmonary manifestations in severe group were significantly higher than those in mild group(P＜0.05),there were no significant differences in gender,white blood cell count(WBC),neutrophil ratio and procalcitonin(PCT)between the two groups(P＞0.05).Multivariate logistic regression analysis model showed that,3 years old ≤age＜6 years old,high body temperature,long fever course,CRP elevated,ESR elevated,LDH elevated,cyanosis of lips,positive triconcave sign,pleural effusion,lesion site was the lower lobe,abnormal electrocardiogram and extrapulmonary manifestations were risk factors for the occurrence of SMPP(P＜0.05).ROC curve analysis showed that,the area under the curve(AUC)of the risk warning model was 0.829,the sensitivity was 84.82％,and the specificity was 78.15％,the actual prediction curve of the risk warning model was in good agreement with the prediction curve,the decision curve showed that,the threshold probability range of the model was 4.61％～88.14％.Conclusion:The risk warning model based on clinical multi parameters such as general data,laboratory indicators and imaging indicators has certain predictive value for the occurrence of SMPP.

Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To analyze and predict the biological properties and function of Treponema pallidum OmpH protein by bioinformatics methods, purify the target protein, and prepare polyclonal antibodies. Methods:From January 2024 to February 2025, the research team from the Department of Clinical Laboratory at The First Affiliated Hospital of Hunan Traditional Chinese Medical College (Hunan Province Directly Affiliated Traditional Chinese Medical Hospital) conducted a study employing integrative approaches combining bioinformatics analysis with animal experimentation. During this investigation, the coding sequence of the T. pallidum outer membrane protein H (TpOmpH) was systematically retrieved from the National Center for Biotechnology Information (NCBI) database. And the bioinformatics tools, such as Protparam, Protscale,SignalP 6.0,NetNGlyc-1.0,TMHMM2.0,NetPhos-3.1,SOPMA,AlphaFold3,IEDB,STRING,C-immsim were used to analyze and predict the biological and immunological characteristics of TpOmpH protein. The full length of TpOmpH gene was synthesized and was cloned into the pET28a to construct the recombinant plasmid pET28a-TpOmpH. The the expression of target protein was induced by IPTG and was purified using affinity chromatography. The TpOmpH protein was used to immunize mice and the anti-serum was harvested, then the titer of antibody was detected. Results:TpOmpH is a hydrophobic outer membrane protein with a molecular weight of 19.7 kDa and strong stability. The TpOmpH protein is located outside the cell membrane and contains 11 serine, 4 threonine, and 1 tyrosine phosphorylation site, but no glycosylation sites. The 77.91% of the amino acids in TpOmpH protein are alpha helix, 8.72% are extended strand, 10.47% are random coils, and 2.91% are beta turns. The tertiary structure predicted by AlphaFold3 is in its optimal state. The TpOmpH protein has 4 CTL epitopes, 4 linear epitopes, and 5 spatial epitopes. The TpOmpH protein can interact with Tp92,MutS,SurA,TPANIC_0600 and other proteins which may be involved in Tp invasion. TpOmpH protein can induce an increase in B cell count, antibody content, Th cell count, NK cell count, as well as the expression of various cytokines. High purity TpOmpH protein was obtained through Ni 2+ affinity chromatography, which is consistent with the theoretical molecular weight. TpOmpH protein can induce mice to secrete polyclonal antibodies with antibody titers higher than 1∶10 000. Conclusion:TpOmpH protein is a hydrophobic protein located on the outer membrane of Tp, can induce mice to secrete high titer antibodies, which providing experimental basis for the pathogenesis of Tp and vaccine development.