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.

To clarify the current situation of ketosis in dairy cattle on large-scale pastures in China and provide new insights,a questionnaire survey was conducted to analyze the incidence,preven-tion,treatment methods,and associated costs of ketosis in 79 large-scale pastures.The results showed that the average incidence of ketosis in dairy cows was 3.97％,with a cure rate of 92.40％.The order of importance of methods for preventing and controlling ketosis was as follows:feed for-mulation optimization＞blood ketone monitoring＞negative energy balance monitoring＞feed in-take monitoring＞milk yield monitoring.The most important treatment methods are intravenous glucose＞propylene glycol butyl phosphate＞vitamins＞choline.The most important diagnostic methods are blood ketone testing＞milk ketone testing＞negative energy balance testing＞clinical symptoms＞blood glucose testing.Economic analysis revealed that treatment costs were lower on larger farms and higher milk yields farms.Continuous optimization of feeding management,preven-tion,and control measures should be implemented on large-scale farms in China to reduce the oc-currence of ketosis in dairy cows.Additionally,more effective diagnostic and treatment methods should be employed to improve the cure rate and overall farm income.

AIM:To investigate the effect of plasmin on epithelial sodium channel γ-subunit(γ-ENaC)acti-vation in mouse M-1 cells and the role of nuclear factor-κB(NF-κB).METHODS:Mouse M-1 cells were divided into three experimental parts.In the first part,the cells were divided into a control group,a plasmin group,and a plasmin+BAY 11-7082(NF-κB inhibitor)group to explore the effects of plasmin on inflammatory factors and γ-ENaC.In the sec-ond part,the cells were divided into a control group,a BAY 11-7082 group and a BAY 11-7082+plasmin group.M-1 cells were pretreated with BAY 11-7082 to explore the role of NF-κB in the regulation of γ-ENaC expression by plasmin.In the third part,the cells were divided into a control group,a plasmin group and an interleukin-6(IL-6)group.M-1 cells were treated with plasmin or IL-6 to explore the regulatory effect of IL-6 downstream of NF-κB on γ-ENaC.After drug interven-tion,the levels of IL-6,tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1)and IL-1β in cell culture supernatants were detected by ELISA.The protein levels of phosphorylated inhibitor of nuclear factor-κB α(p-IκBα)/IκBα,p-NF-κB p65/NF-κB p65,and γ-ENaC was detected by Western blot.The distribution of γ-ENaC on the membrane was detected by immunofluorescence staining.RESULTS:Compared with control group,the levels of IL-6,TNF-α,MCP-1 and IL-1β in the supernatants of cells treated with 10 mg/L plasmin for 24 h were increased(n=3,P<0.01),the protein levels of p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC were increased(n=5,P<0.01),and the distribution of γ-ENaC on the membrane was increased.Compared with plasmin group,the levels of IL-6,TNF-α,MCP-1,IL-1β,p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC,and the γ-ENaC distribution on the membrane were lowered in plasmin and BAY 11-7082 coculture group(n=3,P<0.05 or P<0.01).Compared with control group,the ratio of p-NF-κB p65/NF-κB p65 decreased in BAY 11-7082 group(n=5,P<0.05),whereas there was no significant change in γ-ENaC.After stimulation with plasmin,the levels of p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC in-creased(n=5,P<0.05 or P<0.01),and the γ-ENaC distribution on the membrane increased.Treatment with IL-6,downstream of NF-κB,increased the protein expression of γ-ENaC(n=5,P<0.05)and the distribution of γ-ENaC on the membrane after 24 h of intervention.CONCLUSION:The regulation of γ-ENaC expression by plasmin in mouse M-1 cells is related to the abnormal increase in inflammatory factors after NF-κB activation.

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.

AIM:To investigate the effect of plasmin on epithelial sodium channel γ-subunit(γ-ENaC)acti-vation in mouse M-1 cells and the role of nuclear factor-κB(NF-κB).METHODS:Mouse M-1 cells were divided into three experimental parts.In the first part,the cells were divided into a control group,a plasmin group,and a plasmin+BAY 11-7082(NF-κB inhibitor)group to explore the effects of plasmin on inflammatory factors and γ-ENaC.In the sec-ond part,the cells were divided into a control group,a BAY 11-7082 group and a BAY 11-7082+plasmin group.M-1 cells were pretreated with BAY 11-7082 to explore the role of NF-κB in the regulation of γ-ENaC expression by plasmin.In the third part,the cells were divided into a control group,a plasmin group and an interleukin-6(IL-6)group.M-1 cells were treated with plasmin or IL-6 to explore the regulatory effect of IL-6 downstream of NF-κB on γ-ENaC.After drug interven-tion,the levels of IL-6,tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1)and IL-1β in cell culture supernatants were detected by ELISA.The protein levels of phosphorylated inhibitor of nuclear factor-κB α(p-IκBα)/IκBα,p-NF-κB p65/NF-κB p65,and γ-ENaC was detected by Western blot.The distribution of γ-ENaC on the membrane was detected by immunofluorescence staining.RESULTS:Compared with control group,the levels of IL-6,TNF-α,MCP-1 and IL-1β in the supernatants of cells treated with 10 mg/L plasmin for 24 h were increased(n=3,P<0.01),the protein levels of p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC were increased(n=5,P<0.01),and the distribution of γ-ENaC on the membrane was increased.Compared with plasmin group,the levels of IL-6,TNF-α,MCP-1,IL-1β,p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC,and the γ-ENaC distribution on the membrane were lowered in plasmin and BAY 11-7082 coculture group(n=3,P<0.05 or P<0.01).Compared with control group,the ratio of p-NF-κB p65/NF-κB p65 decreased in BAY 11-7082 group(n=5,P<0.05),whereas there was no significant change in γ-ENaC.After stimulation with plasmin,the levels of p-IκBα/IκBα,p-NF-κB p65/NF-κB p65 and γ-ENaC in-creased(n=5,P<0.05 or P<0.01),and the γ-ENaC distribution on the membrane increased.Treatment with IL-6,downstream of NF-κB,increased the protein expression of γ-ENaC(n=5,P<0.05)and the distribution of γ-ENaC on the membrane after 24 h of intervention.CONCLUSION:The regulation of γ-ENaC expression by plasmin in mouse M-1 cells is related to the abnormal increase in inflammatory factors after NF-κB activation.

Objective To analyze the geographical distribution characteristics of TCM syndromes of coronary heart disease in the elderly based on the literature;To summarize the characteristics of TCM syndromes of coronary heart disease patients in different geographical areas;To provide evidence-based data for the standardization of TCM syndromes and syndrome differentiation treatment of coronary heart disease in the elderly.Methods Literature on TCM syndrome of coronary heart disease in the elderly was retrieved from CNKI,Wanfang Data,VIP,CBM and PubMed,from the establishment of each database to December 31,2024.The common TCM syndrome types,syndrome frequency and regional distribution of coronary heart disease in the elderly were statistically analyzed.Results Forty articles were included,with a total number of 6 447 cases and a male-to-female ratio of 1.1∶1.The top 5 highest percentage of co-morbidities of coronary artery disease in the elderly were 1 308 cases of hypertension(24.11%),1 022 cases of type 2 diabetes mellitus(18.84%),787 cases of respiratory disease(14.51%),517 cases of heart failure(9.53%),and 348 cases of hyperlipidemia(6.41%).The top 5 TCM syndromes in elderly patients with coronary heart disease included 779 cases of qi deficiency and blood stasis(12.08%),692 cases of qi-yin deficiency(10.73%),367 cases of phlegm-blood stasis(5.69%),363 cases of heart blood stagnant blockade(5.63%),and 343 cases of qi stagnation and blood stasis(5.32%).The distribution of TCM syndromes in different regions was characterized by qi deficiency,blood stasis and phlegm stasis in the northeast;qi deficiency,blood stasis and qi yin deficiency in the north;qi deficiency,blood stasis and phlegm internal obstruction in the east;qi and yin deficiency and heart blood stasis in the central;qi deficiency,blood stasis and phlegm stasis in the south;phlegm and yin paralysis obstruction,qi and yin deficiency in the southwest;stasis blockage of the cardiac veins,qi yin deficiency in the northwest.The overall trend was that the number of syndromes in the north was higher than that in the south;the number of syndromes in the east,centre and west was decreasing.The distribution of yin deficiency syndrome was highest in the southwest(23.33%)and lowest in the east(10.93%);yang deficiency syndrome was highest in the southwest(13.30%)and lowest in the central(3.32%);qi deficiency and blood stasis syndrome was highest in the northeast(32.89%)and lowest in the northwest(7.24%);the distribution of qi-yin deficiency was highest in the southwest(23.33%)and lowest in the east(7.22%);the distribution of phlegm and stasis syndrome was highest in the northeast(25.67%)and lowest in the east(1.69%).The overall generalization was that deficiency,stasis and phlegm were the main syndrome factors.Conclusion The main symptoms of coronary heart disease in the elderly manifest as a mixture of deficiency and excess,qi deficiency and blood stasis syndrome is the most syndrome type of coronary heart disease in the elderly and is mainly distributed in the northeast.The distribution of TCM syndromes has regional characteristics.

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*

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*