BackgroundObsessive-compulsive disorder （OCD） carries a considerable disability burden. Intolerance of uncertainty （IU） is associated with the severity of obsessive-compulsive symptoms， yet its neural underpinnings remain unclear. The cerebellum has been implicated in uncertainty processing and demonstrates structural and functional abnormalities in OCD， but direct evidence linking its spontaneous activity to the relationship between IU and obsessive-compulsive symptoms is still lacking. ObjectiveTo explore the pathway through which spontaneous cerebellar neural activity mediates the relationship between IU and obsessive-compulsive symptoms in OCD patients， with the aim of providing a new perspective for understanding the neural mechanisms of OCD. MethodsA total of 51 patients with OCD who visited the Mental Health Center outpatient clinic of the General Hospital of Ningxia Medical University from November 2022 to November 2024 and met the diagnostic criteria for OCD according to the International Classification of Diseases， tenth edition （ICD-10）. During the same period， 43 community-based volunteers matched for gender and age were enrolled as the control group. Resting-state functional magnetic resonance imaging data were collected from two groups. Amplitude of low-frequency fluctuation （ALFF） analysis was used to compare whole-brain spontaneous neural activity between two groups. Clinical assessments were conducted using the Yale-Brown Obsessive Compulsive Scale （Y-BOCS） and the Intolerance of Uncertainty Scale-12 （IUS-12）. Pearson correlation analysis was used to examine correlations between cerebellar ALFF values and scale scores in OCD patients. Using IU as the independent variable， obsessive-compulsive symptoms as the dependent variable， and ALFF values from between-group difference brain regions as the mediator， Process 4.0 for SPSS 24.0 （model 4） was used to examine the mediating role of these ALFF values between IU and obsessive-compulsive symptoms. The Bootstrap method was used to test the mediation effect. ResultsA total of 47 OCD patients and 40 controls completed this study. Compared with the control group， the OCD group showed decreased ALFF values in the right cerebellar Crus Ⅱ （t=-5.254， FWE-corrected P<0.01）. Correlation analysis revealed that ALFF value in the right cerebellar Crus Ⅱ was negatively correlated with Y-BOCS total score （r=-0.851）， compulsive behavior subscale score （r=-0.647）， IUS-12 total scores （r=-0.617）， and prospective IU subscale scores （r=-0.717） in OCD group （P<0.01）. Prospective IU subscale scores were positively correlated with Y-BOCS total scores （r=0.811） and compulsive behavior subscale score （r=0.535） （P<0.01）. Mediation analysis showed that ALFF value in the right cerebellar Crus Ⅱ region partially mediated the effect of prospective IU on obsessive-compulsive behavior， with a mediation effect of 0.064 （95% CI： 0.004–0.136）， accounting for 24.57% of the total effect. ConclusionPatients with OCD showed reduced spontaneous neural activity in the right cerebellar Crus Ⅱ region， which was significantly associated with IU and obsessive-compulsive symptoms. This region partially mediated the effect of IU on compulsive behaviors. ［Funded by Basic Conditions and Innovation Platform Construction Project of Ningxia Hui Autonomous Region in 2023 （number， 2022YXGCJS001）］

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective:To evaluate the safety and efficacy of secondary transport on extracorporeal membrane oxygenation (ECMO) for critically ill children.Methods:This was a retrospective cohort study. Data from 222 pediatric patients who underwent ECMO transport from May 2019 to May 2024 at 5 ECMO centers and Chinese Database of Pediatric Extracorporeal Life Support Organization were collected. The cases were divided into primary and secondary transport groups by nature of transport. The clinical data, including demographics, ECMO indications, transport distance, pre-transport lab results, prognosis and complications were analyzed. Two independent samples t-test, Wilcoxon test, and χ2 test or Fisher′s exact probability method were used to compare the differences between 2 groups and evaluate the safety and efficacy of secondary transport. Results:Among the 222 children transported with ECMO, there were 135 males and 87 females, with an age of 3.0 (0.2, 7.0) years. There were 202 cases in the primary transport group and 20 cases in the secondary transport group. All secondary transport patients had failed attempts at weaning ECMO before transfer. The patients in the secondary transport group were older, had higher rates of surgical cannulation, circulatory support, and pre-ECMO lactate levels compared to the primary transport group (7.0 (2.8, 10.0) vs. 3.0 (0.2, 6.0) years old, 55.0% (11/20) vs. 3.6% (7/202), 80.0% (16/20) vs. 41.6% (84/202), (10±4) vs. (7±6) mmol/L, Z=3.41, χ 2=66.31, 10.99, t=2.24, all P<0.05). In the secondary transport group, the vasoactive-inotropic scores of patients on circulatory support and the oxygenation index for patients requiring respiratory support were higher than those in the primary transport group (83±33 vs. 82±68, 51.0±1.8 vs. 37.4±10.2, t=2.36, 2.63, respectively; both P<0.05). There were no statistically significant differences between the 2 groups in sex, transport distance, pre-ECMO creatinine, arterial blood gas BE values, and ECMO duration (all P>0.05). No life-threatening complications occurred during the transport in either group. Two patients in the secondary transport group underwent heart transplantation, and 1 patient underwent radiofrequency ablation. The overall survival rate between the 2 groups showed no statistically significant difference (45.0% (9/20) vs. 55.4% (112/202), χ2=1.15, P>0.05). Conclusions:Secondary ECMO transport for critically ill children don't increase mortality or life-threatening complications during transport. ECMO patients who cannot receive effective treatment locally can benefit from secondary transport to an advanced ECMO center provides further treatment opportunities.

Objective To develop an expert consensus on the subcutaneous injection of targeted drugs for breast cancer,to guide clinical nursing practice.Methods A consensus building group was established to create the initial draft of the consensus based on a review of literature.From December 2023 to February 2024,a total of 84 experts from various fields including breast cancer clinical nursing or medical practice,pharmacology,cancer hospital nursing or medical management were invited to participate in 2 rounds of expert letter consultations.Additionally,an on-site expert discussion meeting and an online expert finalization meeting were conducted to finalize the draft"consensus".Results The finalized consensus includes sections covering basic drug introduction,drug injection nursing(injection personnel,injection preparation,injection points,observation and recording after injection),nursing care for adverse reactions,patient education and follow-up.Conclusion This consensus is scientific and practical.It can serve as a valuable reference for clinical practice related to subcutaneous therapy using targeted drugs for breast cancer.

The lung collaterals form a network that branches from the lung meridian, traversing the lung system and extending across the body′s surface. Lung collateral disease refers to the structural alterations or dysfunction in these collaterals caused by external or internal pathogens. Research into the structural and physiological functions of children′s lung collaterals, as well as the pathogenesis and syndrome differentiation for treating lung collateral diseases in children, holds significant value in guiding the prevention and treatment of pediatric respiratory conditions. Drawing on the theory of collateral disease, the clinical insights of both historical and contemporary physicians, and modern research findings—while considering the unique physiological and pathological characteristics of children′s respiratory systems—this study provides a foundational summary of the morphology and spatial distribution of children′s lung collaterals. The characteristics of these collaterals are highlighted as thin, sparse, short, narrow, brittle, and tender. From this structural understanding, the unique physiological functions of children′s lung collaterals are analyzed. The study further explores the interactions between pathogenic factors and lung collaterals, elucidating the pathogenesis and progression of children′s lung collateral diseases. It proposes treatment principles centered on "seeking treatment in the collaterals and employing the method of unblocking collaterals, "which align with the unique features of pediatric lung collaterals. Common treatment approaches, and relevant prescriptions for managing these diseases are summarized. This paper lays the foundation for a theoretical system encompassing the structure, function, pathogenesis, and syndrome differentiation for treating children′s lung collateral diseases. It offers valuable insights for the clinical diagnosis and management of pediatric respiratory diseases linked to collateral dysfunction and serves as a reference for the systematic development of a broader theoretical framework for children′s collateral diseases.

Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.

The scientific interpretation of the theory of medicinal properties of TCM is a research hotspot in the modernization of TCM. It is of great value to clarify the property and degree of cold and heat in Chinese materia medica for guiding clinical precise medication. In recent years, the research on the cold and heat properties of Chinese materia medica has been carried out at the animal, cell and molecular levels. Based on the objective material basis of medicinal properties, from the perspective of biological effects such as thermodynamics and multiomics; with the help of infrared thermal imaging and other technologies for analysis; forming a variety of research models such as "property-structure relationship". Related research has developed from a single material component or index to a new model that tends to integrate multi-source information and multi-dimensional data. However, how to deal with the problems of large sample size, strong redundancy, high heterogeneity, and how to integrate multi-dimensional information are still research difficulties. With its powerful computing and learning ability, machine learning can show good discrimination and prediction ability in the study of cold and hot properties of Chinese materia medica, and play an important role in the study of cold and hot properties of Chinese materia medica. At present, the most widely used algorithms are linear discriminant analysis, Logistic discriminant analysis, support vector machine, decision tree, random forest and so on. The data dimension of the existing research needs to be enriched, the algorithm has room for further optimization, and a more detailed discriminant model of cold and hot properties of Chinese materia medica needs to be established.

Objective:To construct a health education checklist for safety management of oral antitumor drugs in tumor patients, so as to provide a guidance for clinical nurses in practice, thereby improving the drug safety of patients taking oral antitumor drugs.Methods:Based on the cognition-behavior theoretical framework, a preliminary draft of a health education checklist for safety management of oral antitumor drugs in tumor patients was developed through literature review. The Delphi method was used to conduct consultations with 17 experts from July to September 2024 to revise and add or delete the contents of the checklist based on the experts' assignments of importance to the indicators at each level and the textual comments made.Results:A total of two rounds of expert consultation were conducted. The final established health education checklist for safety management of oral antitumor drugs in tumor patients included 4 primary and 28 secondary indicators. In the two rounds of consultation, the positive coefficient of experts was 100.0%, the coefficient of expert authority was 0.93, the coefficients of variation for the two rounds of expert ratings were 0 to 0.173 and 0 to 0.151, and the coefficients of Kendall's concordance were 0.141 (χ 2=74.461, P<0.001) and 0.113 (χ 2=59.549, P=0.002) , respectively. Conclusions:The health education checklist for safety management of oral antitumor drugs in tumor patients has good scientific, reliable and clinical practical value, which can provide scientific, standardized and convenient practical guidance for clinical nurses to implement health education on drug safety management for patients taking oral antitumor drugs.