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.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

ObjectiveTo enhance teaching in postoperative cancer rehabilitation, this study developed an integrative Chinese-Western medicine postoperative oncology rehabilitation system, termed the medical oncology generative pre-trained transformer (MedOncoGPT). By introducing MedOncoGPT as an intelligent assistant, an integrated teaching model combining Chinese and Western medicine was established. The study evaluated its impact on students’ integrative clinical reasoning and practical abilities, providing support for instructional reform in related courses. MethodsUsing teaching resources as the knowledge base, MedOncoGPT was built upon the open-source ChatGLM model and incorporated Low-Rank Adaptation (LoRA) fine-tuning and retrieval-augmented generation (RAG) techniques to address postoperative integrative oncology scenarios. The system was applied in courses and clinical clerkships related to integrative oncology. In alignment with course objectives, a five-stage instructional process—pre-class preparation, in-class inquiry, simulated multidisciplinary consultation, clinical reinforcement, and teaching reflection—was designed to guide students in completing syndrome differentiation, comprehensive assessment, and follow-up planning within real or simulated case contexts. Comparative analyses of student engagement, syndrome differentiation thinking, evidence-based awareness, and interdisciplinary integration skills before and after the teaching reform were conducted using questionnaires, course assessments, classroom observations, and semi-structured interviews. ResultsFollowing the implementation of MedOncoGPT, students demonstrated improved performance in case analysis, prescription formulation, and integrative Chinese-Western medical evaluation compared with those receiving traditional instruction. Classroom participation and the relevance of student inquiries also increased. Self-assessment results indicated high levels of satisfaction with respect to clarity of integrative clinical reasoning, ability to retrieve and apply guideline-based evidence, and awareness of appropriate use of intelligent tools in clinical decision-making. More than 92% of students reported that the system facilitated understanding of abstract theoretical concepts presented in textbooks. Instructors noted that the system helped reduce lesson preparation time, enriched typical case materials and discussion scenarios, and promoted the translation of research findings into classroom teaching. Pilot data showed that, with MedOncoGPT assistance, the mean time for initial syndrome differentiation decreased from 18.4 min to 12.1 min, and the agreement rate increased from 68.3% to 82.5%. In the teaching pilot, the experimental group achieved a higher mean score on the final case analysis assessment than the control group (82.6 vs. 74.3). ConclusionThe integration of MedOncoGPT into teaching on postoperative integrative cancer rehabilitation enabled the establishment of a stable instructional process within existing curricula and enhanced students’ integrative clinical reasoning and evidence-based practice capabilities. The approach demonstrates positive potential for advancing the integration of research, clinical practice, and education and represents a valuable exploratory strategy for instructional reform in courses on integrative Chinese-Western medicine.

Objective:To construct a predictive model for mortality in patients with multiple trauma combined with thoracic injuries and evaluate its predictive value.Methods:A retrospective cohort study was conducted to analyze the clinical data of 184 patients with multiple trauma combined with thoracic injuries admitted to the International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from April 2019 to December 2023, including 129 males and 55 females, aged 19-85 years [(46.1±13.7)years]. According to the prognostic outcomes at 3-month follow-up after discharge, the patients were divided into survival group ( n=145) and death group ( n=39). Data were recorded in both groups at admission, including gender, age, and cause of injury, laboratory tests such as systolic blood pressure, oxygen saturation (SaO 2), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), and lactate, combined injuries such as the number of combined injuries, number of rib fracture, bilateral rib fracture, first-rib fracture, sternum fracture, thoracic vertebral fracture, bilateral pulmonary contusion, bilateral pneumothorax, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, skull fracture, skull base fracture, cervical vertebral fracture, brain herniation, cerebral contusion, lumbar vertebral fracture, pelvic and abdominal cavity hematoma, liver injury, kidney injury, spleen injury, clavicle fracture, scapular fracture, femoral fracture, and pelvic fracture, and injury scores such as shock index (SI), modified shock index (MSI), injury severity score (ISS), revised trauma score (RTS), Glasgow coma score (GCS), and thoracic trauma severity (TTS) score. Univariate binary logistic regression analysis was used to screen for risk factors of death in patients with multiple trauma combined with thoracic injuries. LASSO regression and multivariate logistic regression analysis were employed to identify predictive variables and independent risk factors for mortality in those patients and to construct a regression equation. A nomogram prediction model based on the regression equation was developed using R language. Receiver operating characteristic (ROC) curves were plotted to evaluate the discrimination of the model. The ROC curves were internally validated using the Bootstrap method with 1 000 resamples. The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test. The clinical application value of the model was evaluated using decision curve analysis (DCA) and clinical impact curve (CIC) analysis. Results:There were statistically significant differences between the survival group and the death group in systolic blood pressure, SaO 2, NLR, lactate, number of combined injuries, subarachnoid hemorrhage, subdural hematoma, skull fracture, skull base fracture, brain herniation, liver injury, SI, MSI, ISS, RTS, GCS, and TTS ( P<0.05 or 0.01). The results of the univariate binary logistic regression analysis showed that the above-mentioned related variables except for systolic blood pressure were all significantly associated with death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Five predictive variables, TTS, GCS, brain herniation, ISS, and lactate were obtained in LASSO regression analysis. The results of the multivariate logistic regression analysis showed that GCS ( OR=0.70, 95% CI 0.58, 0.83), brain herniation ( OR=46.18, 95% CI 4.27, 499.26), TTS ( OR=1.71, 95% CI 1.30, 2.24), and lactate ( OR=1.35, 95% CI 1.01, 1.80) were independent risk factors for death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Based on the aforementioned independent risk factors, a regression formula was constructed as follows: P=e x/(1+e x), with the x=-0.36×"GCS"+3.83×"brain herniation"+0.53×"TTS"+0.30×"lactate levels"-11.03. The area under the ROC curve (AUC) of the predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on the equation was 0.97 (95% CI 0.93, 1.00). The AUC was internally validated using the Bootstrap method with 1 000 samples, resulting in an AUC of 0.97 (95% CI 0.91, 1.00). The results of the H-L goodness-of-fit test showed that the bias-corrected calibration curve of the model was in good consistence with the actual curve and both of them were close to the ideal curve. In the evaluation of the clinical application value of the predictive model, the DCA results showed that the predictive model could achieve good clinical net benefit. The CIC results showed that when the threshold probability was greater than 0.7, the model-identified high-risk patients for death highly matched the patients who actually died. Conclusion:The predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on GCS, brain herniation, TTS, and lactate has good predictive performance and clinical application value.

Objective:To establish a Zika virus-infected suckling SD rat model with type Ⅰ interferon receptor deficiency（SD-Ifnar1 -/-［cc］）and provide a novel animal model for investigating Zika virus pathogenesis and developing therapeutic strategies. Methods:Seventeen-day-old male SD-Ifnar1 -/-［cc］rat pups were randomly divided into experimental and control groups（ n=6）. The experimental group received an intraperitoneal injection of Zika virus strain SZ-wiv01（5×10 4 PFU/rat，200 μl），while the control group received an equal volume of phosphate-buffered saline（PBS）. Animals were euthanized via CO 2 asphyxiation on days 12 and 15 post-infection（dpi），and brain，spleen，liver，and testis tissues were harvested. Viral loads and cytokine expression levels were quantified using quantitative real-time PCR qRT-PCR），and histopathological evaluation was performed via HE staining. Results:qRT-PCR analysis revealed no detectable Zika virus RNA（Ct >35）in control tissues. In the experimental group，viral RNA（Ct <35）was detected in the brain，spleen，liver，and testis by day 12，with stable viral loads across tissues by day 15（ P>0.05）. Cytokine profiling demonstrated significant upregulation in the brain at day 12：IFN-β（5.58-fold， P<0.01），IL-6（7.11-fold， P<0.01），and CCL5（3.79-fold， P<0.01）. By day 15，these levels remained elevated（IFN-β：3.07-fold；IL-6：4.04-fold；CCL5：5.22-fold；all P<0.01）. In the liver，IFN-β mRNA decreased to 20% of the control level by day 15（ P<0.05），while IL-6 declined to 24% and CCL5 mRNA dropped to 38% by day 12. No significant cytokine changes were observed in the spleen（ P>0.05）. Testicular tissues exhibited reduced IFN-β mRNA levels（43% of control at day 12，31% at day 15； P<0.05）. Histopathological analysis revealed marked splenomegaly with disrupted splenic corpuscle architecture and lymphocyte depletion，significant inflammatory cell infiltration in hepatic portal areas，and testicular structural disorganization with inflammatory infiltration in Zika-infected rats. Conclusions:The SD-Ifnar1 -/-［cc］suckling rat model is successfully established and validated. This model recapitulates systemic Zika virus infection，tissue-specific pathology，and immune response dynamics，providing a robust platform for elucidating viral pathogenesis and advancing antiviral drug development.

This study established a droplet digital PCR(ddPCR)EvaGreen assay and probe methods for Schistosoma japonicum detection,and evaluated their application in detecting early infections in the S.japonicum host oncomelania and mice.Primers and corresponding probes for both ddPCR methods were designed and synthesized,and plasmids containing target sequences were constructed.The sensitivity of the two methods was tested through detection of the corresponding plasmids,and infectious and mixed oncomelania genomic DNA.Their specificity was evaluated by the detection of genomic DNA of negative oncomelania,Schistosoma mansoni,Clonorchis sinensis,Spirometra mansoni,and S.japonicum(as a positive control).The ddPCR probe method was evaluated by detection of early infection of oncomelania exposed tomiracidium with various ratios and incubation times,and the early migration and distribution of cercaria or schistosomula in mouse hosts infected with 200 cercaria via abdominal skin contact.According to standard curves constructed through the detection of plasmid serial dilutions,the regression equation for the EvaGreen assay was y=-0.839 9x+7.050 9,with a correlation coefficient R2=0.988 1,and the regression equation for the probe method was y=-1.047 5x+7.255 1,with a correlation coefficient R2=0.999 8.The lowest limit of plasmid detection with the probe method was between 38.94 cp/μL and 194.74 cp/μL.Both methods successfully detected positive reactions in the genomic DNA samples of infectious oncomelania at concentrations above 0.002 ng/μL and in the genomic DNA of each group of oncomelania mixtures.No significant differences between probe methods were observed in the detection values in the control group and the genomic DNA of negative oncomelania,S.mansoni,C.sinensis,and S.mansoni.However,the detection value of genomic DNA of negative oncomelania(291 ng/μL)with the EvaGreen assay was(20.3±4.39)cp/μL,a value significantly higher than the(1.5±0.1)cp/μL observed in the control group.For detection of early infection in oncomelania,the probe method detected Schistosoma japonicum DNA after 30 s incubation at room temperature with a≥5∶1 ratio of miracidium to oncomelania;the detection value peaked after a short time(5 min),and the peak value showed a fold increase similar to the increase in the miracidium to oncomelania ratio.Detection of early stage infection in mice with the probe method revealed that the schistosomula entered the lungs on day 2 and the liver on day 4,and continually migrated within the organs with abundant blood supply(spleen,kidney,and brain)in the first 9 days;moreover,a tendency toward ectopic parasitism was observed in the heart and pancreas on day 9,and a constantly negative control level was observed in the testes.The ddPCR probe method was more accurate and specific than the EvaGreen assay in the detection of plasmids,and infectious and mixed oncomelania,and the latter showed non-specific reactions in negative oncomelania detection.In a practical application,the probe method was demonstrated to be sensitive,to effectively reflect the early infection of oncomelania,and to reveal schistosomula migration and distribution in multiple organs of infected mice.

This study was aimed at investigating differentially expressed genes(DEGs)in Clonorchis sinensis(C.sinensis)meta-cercariae and newly excysted juveniles(NEJs)cultured in vitro for 1 hour or 3 hours,through transcriptomic analysis.Our objective was to explore the mechanisms underlying host invasion.Metacercariae were digested and isolated from Pseudorasbora parva infected with C.sinensis.The metacercariae excysted and developed into NEJs in vitro.Subsequently,the mRNA of metacercariae and NEJs cultured in vitro for 1 hour or 3 hours was extracted for transcriptomic sequencing analysis to screen for DEGs,and to conduct GO and KEGG analyses.A protein-protein interaction network(PPI)was constructed to identify hub genes.A total of 1 218 DEGs were de-tected.The main enriched GO terms of DEGs included transcription regulator activity and gated channel activity(primarily K+).The KEGG pathways significantly enriched in DEGs included cholesterol metabolism,lysosome,synthesis,secretion,and action of para-thyroid hormone.ZFAND4-2,BIRC6,and other genes were screened and identified as hub genes through PPI network analysis.Addi-tionally,abundant differential expression of cathepsin-related genes,including Cathepsin L and Cathepsin F,were observed before and after excystment in C.sinensis.Therefore,significant transcriptional level changes occurred in the metacercariae of C.sinensis be-fore and after excystation,and enrichment was observed primarily in signaling pathways,such as activation of growth and material me-tabolism,that regulate parasite growth and development.Meanwhile,biological events conducive to parasite invasion,migration,and adhesion were triggered.

AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.

Objective:To prepare rabbit polyclonal antibody against human FAM21 and analyze antibody specificity.Methods:Using the plasmid encoding human FAM21 full-length gene as a template,the nucleotide sequence of its 2 431～3 006 base was amplified by PCR and connected to the pGEX-6p-1 prokaryotic expression vector to construct pGEX-6P-1-FAM21 recombinant plasmid expressing the 811～1 002 amino acid fragment of FAM21.The recombinant plasmid was transformed into BL21(DE3)compe-tent Escherichia coli and was expressed inductively,and the protein was purified using GST fusion protein purification magnetic beads.The purified GST fusion protein was used as an antigen to immunize New Zealand rabbits,and the collected antiserum was purified by an agarose column containing GST protein.The specificity of antibody was detected by Western blot and immunofluorescence assay in stable FAM21 knockdown HeLa cells.Results:The pGEX-6p-1-FAM21 prokaryotic expression plasmid was successfully constructed and induced to express in BL21(DE3)competent Escherichia coli.The purified GST fusion protein had a molecular weight of approxi-mately 50 kD,and the purified antibody titer from immunized New Zealand rabbits was greater than 1∶128 000,with high specificity.Conclusion:The pGEX-6p-1-FAM21 prokaryotic expression plasmid is successfully constructed,and the rabbit polyclonal antibody against human FAM21 is prepared for Western blot and immunofluorescence assay.

Objective The aim of this study was to analyze the proportion of disability adjusted life years(DALYs)attributed to aging population in common digestive system malignancies in China,and predict the proportion and the trends of DALYs attributed to aging proportion from 2022 to 2046.Methods Based on the Global Burden of Disease Study 2021,the DALY data of esophageal cancer,stomach cancer,colorectal cancer,pancreatic cancer,liver cancer,gallbladder and biliary tract cancer of Chinese people aged≥25 years from 1990 to 2021 were selected.The age-period-birth models were used to predict the DALY of malignant tumors from 2022 to 2046.The changes of DALY from 1990 to 2046 were decomposed into population growth,population aging,and age-specific DALY rate changes,and analyze the proportion of DALY changes attributable to population aging and its change trend.Results From 1990 to 2021,the DALY change rates of esophageal cancer,stomach cancer,colorectal cancer,pancreatic cancer,liver cancer,gall-bladder and biliary tract cancer in Chinese people aged≥25 years were 18.20％,-0.34％,98.10％,164.16％,58.21％and 90.62％,respectively.Compared with 2021,the proportion of DALY changes attributed to population aging for six types of malignant tumors in 1990 was from-38.32％to-19.72％.The top three cancer types with the highest attribution ratios were stomach cancer(-38.32％),esophageal cancer(-38.07％),gallbladder and biliary tract cancer(-29.78％).The expected change rates of DALY for the six types of malignant tumors from 2021 to 2046 were 20.72％,11.50％,58.19％,57.38％,21.36％and 48.39％,respective-ly.By compared with 2021,the proportion of DALY changes of six malignant tumors attributed to population aging in 2046 was from 18.82％to 47.83％,and the top three cancers attributed to the proportion were gallbladder and biliary tract cancer(47.83％),color-ectal cancer(43.07％)and pancreatic cancer(38.76％).From 2022 to 2046,the proportion of DALY changes attributed to aging pop-ulation for the six types of malignant tumors would continue to rise(P＜0.001).The proportions of colorectal cancer and pancreatic cancer attributed to population aging and the proportion of age-specific DALY rate were both positive and rising(P＜0.001),which would eventually promote the further increase of DALY.Conclusion Population aging has become the main driving factor for the growth of DALY in digestive system malignant tumors in China.The impact on DALY of colorectal cancer and pancreatic cancer will be prominent in the future.Targeted prevention and control strategies should be developed to actively respond to population aging.