Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

Objective To explore the peak moment characteristics of lower limb joints,as well as the contribution rate and compensation mechanism of lower limb joints when older adults with a history of falls cross obstacles at different paces.Methods Thirty healthy older adults and 30 eldely fallers were recruited.The Qualisys infrared high-speed motion capture system and the Kistler three-dimensional force platform were used to collect the biomechanical data of the older adults when they crossed an obstacle with a height of 15％of their height at three walking speeds(1.05,1.41,1.74 m/s).The data were then modeled and analyzed using Visual 3D software.Results As walking speed increased,the peak knee extension moment,peak ankle plantar flexion moment,and double peak value of hip flexion moment in healthy group all increased significantly(P＜0.05).Compared with healthy group,the double peak values of hip flexion moment in faller group were significantly smaller than those in healthy group(P＜0.05).During walking at moderate speed,the contribution rate of the left hip joint in faller group was significantly higher than that of healthy group(P=0.025),while the contribution rate of the ankle joint was significantly lower(P=0.044).The margin of stability in the anterior-posterior direction at the moment of ground contact of the stance leg and the stride leg increased with walking speed(P=0.007,P=0.002).Conclusions Compared with healthy older adults,the elderly fallers have lower peak torque,peak ground reaction force,and dynamic stability in the anterior-posterior direction.As the walking speed increases,the mechanical parameters and the margin of stability of older adults increase significantly,and walking stability is improved.Compared with healthy older adults,elderly fallers usually rely more on the contribution of hip joint movements and reduce the involvement of ankle joints.It is recommended to incorporate fast walking exercises into the daily fall prevention exercise program for older adults,with combination of coordinated training of the hip,knee,and ankle joints.

Objective To explore the peak moment characteristics of lower limb joints,as well as the contribution rate and compensation mechanism of lower limb joints when older adults with a history of falls cross obstacles at different paces.Methods Thirty healthy older adults and 30 eldely fallers were recruited.The Qualisys infrared high-speed motion capture system and the Kistler three-dimensional force platform were used to collect the biomechanical data of the older adults when they crossed an obstacle with a height of 15％of their height at three walking speeds(1.05,1.41,1.74 m/s).The data were then modeled and analyzed using Visual 3D software.Results As walking speed increased,the peak knee extension moment,peak ankle plantar flexion moment,and double peak value of hip flexion moment in healthy group all increased significantly(P＜0.05).Compared with healthy group,the double peak values of hip flexion moment in faller group were significantly smaller than those in healthy group(P＜0.05).During walking at moderate speed,the contribution rate of the left hip joint in faller group was significantly higher than that of healthy group(P=0.025),while the contribution rate of the ankle joint was significantly lower(P=0.044).The margin of stability in the anterior-posterior direction at the moment of ground contact of the stance leg and the stride leg increased with walking speed(P=0.007,P=0.002).Conclusions Compared with healthy older adults,the elderly fallers have lower peak torque,peak ground reaction force,and dynamic stability in the anterior-posterior direction.As the walking speed increases,the mechanical parameters and the margin of stability of older adults increase significantly,and walking stability is improved.Compared with healthy older adults,elderly fallers usually rely more on the contribution of hip joint movements and reduce the involvement of ankle joints.It is recommended to incorporate fast walking exercises into the daily fall prevention exercise program for older adults,with combination of coordinated training of the hip,knee,and ankle joints.

Objective:To investigate the influencing factors of green procurement for medical equipment,so as to provide theoretical basis and policy insights for promoting practices of green procurement for medical institutions.Methods:Based on literature review and expert interviews,a questionnaire about influencing factors of green procurement for medical equipment was formulated,which was used to conduct questionnaire survey for medical institutions of secondary and tertiary grades in Shandong province.The questionnaire included the measured indicators and basic information of medical institutions from four dimensions:pressure of external system(7 items),leadership support(4 items),organizational inertia(5 items),and collaboration degree of stakeholder(5 items).The Likert 5-level scale was adopted to conduct scoring of questionnaire,and the differences in various influencing factors between secondary grade hospital and tertiary grade hospital were compared and analyzed.Results:The scores of tertiary grade hospital were respectively 4.00(3.14,4.82),4.25(4.00,5.00),and 3.60(3.00,4.00)at pressure of external system,leadership support(4 items),organizational inertia(5 items)of three dimensions,and they were 3.86(3.11,4.14),4.00(3.75,5.00),and 3.20(2.80,3.80)at secondary grade hospital,and the differences of them between secondary grade hospital and tertiary grade hospital were significant(Z=-2.243,-2.654,-2.538,P<0.05).There was not significant difference at the dimension of collaboration degree of stakeholder between secondary and tertiary hospitals(P>0.05).Conclusion:A series of measures,such as adopting policy support with differentiation,establishing multi-level incentive mechanisms,reducing organizational change resistance,and improving multi-party coordination mechanisms,can further promote green procurement of medical institutions.

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*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model. Methods Ferroptosis genes were obtained from FerrDb database, and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database. Transcriptome-Wide Association Study, colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes; Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes. Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer. Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients. The expression levels of genes in pan-cancer were analyzed through the TIMER database. Two prognostic models were conducted, Model 1 included age and tumor stage, while Model 2 incorporated age, tumor stage, and prognostic genes. The predictive capabilities of the two models were compared. Results A total of 91 candidate genes related to ferroptosis were obtained. Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer. CA9, SCD, TFRC, QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients (P＜0.05), while PTPN6, ALOXE3, HELLS, IFNG, MIOX, ALOX12B, DUOX1, ALOX15, AQP3 and IDO1 were protective factors (P＜0.05). The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers, among which TFRC was associated with the largest number of cancer types. Kaplan-Meier analysis showed that HELLS, DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer. The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478, and the AUC of Model 2 was 0.854 and 0.595. Model 2 (C-index = 0.727) had better predictive ability than Model 1 (C-index = 0.502). Conclusion The prognostic model composed of 15 prognostic-related genes selected based on bioinformatics has better predictive performance for the survival outcomes of cervical cancer patients, providing important reference value for the prognostic assessment of cervical cancer patients.

Objective: To analyze the association of eating dining locations and their association with nutritional status among Chinese children aged 6-17 years,so as to provide reference for guiding children s reasonable diet. Methods: Stratified random cluster sampling was used to select children aged 6 to 17 years from 28 cities and rural areas of 14 provinces in East, North, Central, South, Southwest, Northwest, Northeast of China, and a total of 52 535 children were included in the study from 2019 to 2021. Information including dining locations, demographic characteristics, dietary intakes and physical activity were collected through a questionnaire survey. Fasting body height and weight were measured in the morning. Unordered multiclass Logistic regression analysis was conducted to assess the relationship between dining locations and nutritional status in children. Results: Regarding children s dining locations, 66.3% ate breakfast at home,25.8% ate breakfast at school,7.9% ate breakfast outside (small dining tables, restaurants, stalls, etc.); 67.7% ate dinner at home,29.0% ate dinner at school,3.3% ate dinner outside; and 63.6% ate lunch at school,30.8% ate lunch at home,5.7% ate lunch outside. The prevalence rates of overweight/obesity and undernutrition were 28.6% and 9.3%, respectively. The adjusted multiclass Logistic regression analysis (controlling for age, region, parental education, household income, total energy intake, and moderate-to-vigorous physical activity) demonstrated that, compared to eating at home, school based breakfast and dinner consumption was associated with significantly lower overweight/obesity risks for both genders (boys: breakfast OR =0.70, 95% CI =0.65-0.75; dinner OR =0.80, 95% CI = 0.74- 0.86; girls: breakfast OR = 0.89 , 95% CI = 0.82-0.96; dinner OR =0.88, 95% CI =0.81-0.95), whereas eating lunch away from home significantly increased overweight/obesity risks (boys: OR =1.32, 95% CI =1.17-1.48; girls: OR =1.43, 95% CI =1.26- 1.62 ), with all associations being statistically significant ( P <0.05). After adjusting for confounding factors, boys who ate breakfast away from home showed a significantly reduced risk of undernutrition ( OR =0.80,95% CI =0.66-0.97), while those consuming lunch away from home had an increased risk ( OR =1.26, 95% CI =1.01-1.57) ( P <0.05). Conclusions The choice of dining locations for children is becoming more diverse, and a relatively high proportion of children eat meals outside the home and at school. Eating out have a higher risk of malnutrition for children. School feeding may be beneficial to children s physical health.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Objective:To investigate the influencing factors of green procurement for medical equipment,so as to provide theoretical basis and policy insights for promoting practices of green procurement for medical institutions.Methods:Based on literature review and expert interviews,a questionnaire about influencing factors of green procurement for medical equipment was formulated,which was used to conduct questionnaire survey for medical institutions of secondary and tertiary grades in Shandong province.The questionnaire included the measured indicators and basic information of medical institutions from four dimensions:pressure of external system(7 items),leadership support(4 items),organizational inertia(5 items),and collaboration degree of stakeholder(5 items).The Likert 5-level scale was adopted to conduct scoring of questionnaire,and the differences in various influencing factors between secondary grade hospital and tertiary grade hospital were compared and analyzed.Results:The scores of tertiary grade hospital were respectively 4.00(3.14,4.82),4.25(4.00,5.00),and 3.60(3.00,4.00)at pressure of external system,leadership support(4 items),organizational inertia(5 items)of three dimensions,and they were 3.86(3.11,4.14),4.00(3.75,5.00),and 3.20(2.80,3.80)at secondary grade hospital,and the differences of them between secondary grade hospital and tertiary grade hospital were significant(Z=-2.243,-2.654,-2.538,P<0.05).There was not significant difference at the dimension of collaboration degree of stakeholder between secondary and tertiary hospitals(P>0.05).Conclusion:A series of measures,such as adopting policy support with differentiation,establishing multi-level incentive mechanisms,reducing organizational change resistance,and improving multi-party coordination mechanisms,can further promote green procurement of medical institutions.