Both cathartic colon （CC） and cathartic-dependent constipation （CDC） are caused by the abuse of stimulant laxatives， while their concepts are not completely the same.Starting from the disease name of CC， this article traced the origin and evolution of the concept of CC， summarizes and compared the similarities and differences between CC， CDC， and slow transit constipation （STC）， and called for strict differentiation among the three.Furthermore， this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine （TCM） syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established， and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally， the paper provides an overview of current research on CDC in both Western medicine and TCM contexts， identifies future research directions， and suggests research pathways for refining and advancing CDC studies.

ObjectiveTo observe the clinical efficacy of the Yiqi Yangyin Huoxue prescription （YYHP） in the treatment of cathartic colon （CC） and its effects on fecal short-chain fatty acids （SCFAs）， and to explore the correlations among CC severity indicators and between these indicators and patient history. MethodsAccording to the inclusion and exclusion criteria， 98 patients meeting the diagnostic criteria of both traditional Chinese and Western medicine for CC with the syndrome of Qi-Yin deficiency complicated by blood stasis were randomly assigned to an observation group and a control group. The observation group received YYHP granules， while the control group received lactulose. Both medications were administered twice daily， one sachet each time， half an hour after breakfast and dinner， with a treatment course of 8 weeks. The primary constipation symptom score， Patient Assessment of Constipation Quality of Life （PAC-QOL） score， and TCM syndrome score were assessed before and after treatment and at the 8^th week after the end of treatment. The overall clinical effective rate， as well as the efficacy attenuation index and degree， were evaluated. Fecal SCFA levels were measured using gas chromatography-mass spectrometry （GC-MS）. Spearman correlation analysis was performed to explore the correlations among CC severity indicators and between these indicators and patient history. ResultsThe overall clinical effective rate in the observation group （95.83%） was higher than that in the control group （78.72%） （P<0.05）. After treatment， the total scores for primary constipation symptoms， PAC-QOL， and TCM syndromes decreased in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. The severity of all primary constipation symptoms was alleviated in both groups （P<0.05）. In terms of "excessive straining and difficult defecation"， "anal heaviness， incomplete evacuation， and bloating sensation"， "abdominal distension"， and "defecation frequency"， the observation group showed better efficacy than the control group （P<0.05）. Scores of the four PAC-QOL dimensions and the scores and severity of primary and secondary TCM symptoms were reduced in both groups （P<0.05）， with more significant reductions in the observation group （P<0.05）. After treatment， acetic acid， propionic acid， butyric acid， and total SCFAs in the observation group increased significantly （P<0.05）. The efficacy attenuation index and degree in the observation group were lower than those in the control group （P<0.05）. No severe adverse reactions occurred in either group， and there was no statistically significant difference in the incidence of adverse reactions between the two groups. Positive correlations of varying degrees were observed among the total scores of primary constipation symptoms， PAC-QOL， and TCM syndromes， as well as between these scores and the history of stimulant laxative use， disease duration， and age. ConclusionYYHP can effectively alleviate the primary constipation symptoms in CC patients， improve quality of life， and ameliorate TCM syndromes， with good safety. It also has the advantage of a lower rebound degree after drug withdrawal， and its mechanism may be related to increasing fecal SCFA levels. Long-term abuse of stimulant laxatives may aggravate the severity of CC and prolong the disease course.

ObjectiveThe most prevalent mRNA modification, N6-methyladenosine (m⁶A) plays an important role in various RNA metabolism, including gene expression and translation. By recruiting different “reader” proteins and their cofactors, m⁶A modification can affect messenger RNA (mRNA) degradation, splicing, nuclear export and translation. However, the selective mechanism by which m⁶A sites regulate mRNA translation through m⁶A reader YTHDF1 binding remains poorly understood, due to a lack of computational methods for identifying context-specific m⁶A sites that regulate translation. To address this, we developed a novel computational framework named m⁶ATEpre, the first tool designed to predict cell-specific m⁶A sites that regulate translation efficiency. Methodsm⁶ATEpre integrates multi-omics data, introduces a novel feature representation strategy for m⁶A site sequences, and employs an autoencoder to effectively capture embedded feature representations. Specifically, m⁶ATEpre first integrated MeRIP-seq data and PAR-CLIP data through overlapping m⁶A sites with YTHDF1 binding sites and identified YTHDF1-mediated m⁶A sites. Then, m⁶ATEpre detected the translation gene by analyzing the Ribo-seq data under YTHDF1 knockdown vs control condition. Genes whose translation is mediated by YTHDF1 in an m⁶A-dependent manner were identified by a significant decrease in translation efficiency upon YTHDF1 knockdown. Next, we proposed a binary vector indicating the presence or absence of YTHDF1 binding motifs to characterize each m⁶A site sequence. This represents a novel feature representation strategy for m⁶A sites. m⁶ATEpre utilized the autoencoder to extract the potentially important feature representations and constructed a multilayer perceptron neural networks model to predict potential m⁶A sites that regulating translation efficiency. ResultsA comprehensive evaluation of m⁶ATEpre was conducted through a series of experiments. We compared its performance against that of a similar prediction task model, as well as other classifiers. The results indicate that m⁶ATEpre achieved the best prediction performance. In addition, we analyzed different feature representation strategies and performed ablation experiments to validate the rationality of the model design. The results demonstrate that our proposed feature representation strategy has a greater advantage in improving prediction performance. In the HeLa cell line, bioinformatic analysis of the metagene distribution and sequence minimum free energy of m⁶A sites regulating translation efficiency (m⁶A-reg-TE sites) revealed their specific properties in translation regulation. Functional enrichment analysis indicated that m⁶A-reg-TE genes are associated with specific biological processes and KEGG pathways. By integrating the binding sites of YTHDF1 co-factors with m⁶A-reg-TE sites, we revealed that YTHDF1-mediated and m⁶A-dependent translation efficiency regulation requires the cooperation of multiple translation-regulatory RNA-binding proteins among its co-factors in the HeLa cell line. Furthermore, we extended our predictions to the dataset of the HEK293T cell line. Similarly, bioinformatic analysis of the metagene distribution and functional enrichment revealed the cell-specific characteristic of these predicted m⁶A-reg-TE sites in HEK293T cells. Likewise, integrated analysis of multiple YTHDF1 co-factors and m⁶A-reg-TE sites predicted in the HEK293T cell line reveals their m⁶A-dependent cooperation in regulating translation efficiency. Conclusionm⁶ATEpre is a timely tool that will advance our understanding of the mechanisms of m⁶A regulation in translation efficiency. The source code and datasets used in this work can be downloaded from https://www.scidb.cn/s/bAZZFr.

Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

ObjectiveTo conduct a theoretical study on the medical-rehabilitation integration. MethodsStarting from the background, objectives and content of the medical-rehabilitation integration, this study analyzed its innovative points from the dimensions of conceptual innovation, organizational innovation, model innovation and technological innovation. Results and ConclusionThe medical-rehabilitation integration is an innovation in medical services that takes conceptual innovation as the forerunner, organizational innovation as the foundation, model innovation as the carrier and technological innovation as the core.

[摘 要] 目的：探讨lncRNA核内富集丰富转录本1（NEAT1）调控miR-1287-5p/DNA损伤诱导转录本4（DDIT4）轴对卵巢癌SKOV3细胞增殖、凋亡和侵袭的影响及其机制。方法：收集2023年6月至2024年6月期间湖北医药学院附属随州医院手术切除的27例卵巢癌患者的癌及癌旁组织标本，以及正常人卵巢上皮细胞IOSE80和卵巢癌细胞系SKOV3、CAOV3和A2780，RT-qPCR检测卵巢癌组织与细胞中lncRNA NEAT1、miR-1287-5p及DDIT4 mRNA表达。将SKOV3细胞分为Ctrl组、si-NC组、si-NEAT1组、si-NEAT1 + anti-miR-NC组、si-NEAT1 + anti-miR-1287-5p组、si-NEAT1 + vector组、si-NEAT1 + OE-DDIT4组。CCK-8法、克隆形成实验、流式细胞术、Transwell实验分别检测各组细胞增殖、凋亡及侵袭能力，WB法检测细胞中DDIT4、细胞周期蛋白D1（cyclin D1）、p53、迁移侵袭增强子1（MIEN1）蛋白水平。双萤光素酶报告基因验证lncRNA NEAT1与miR-1287-5p/DDIT4靶向结合关系，RNA pull-down实验、RNA免疫沉淀实验分别验证lncRNA NEAT1与miR-1287-5p、miR-1287-5p与DDIT4的靶向结合关系。另设pcDNA组（转染空载体pcDNA3.1）和pc-NEAT1 组（转染pcDNA-NEAT1）以验证NEAT1过表达效应。结果：卵巢癌组织中lncRNA NEAT1、DDIT4 mRNA表达水平显著高于癌旁组织（P < 0.05），而miR-1287-5p表达显著低于癌旁组织（P < 0.05）。敲低lncRNA NEAT1后，与Ctrl组和si-NC组相比，si-NEAT1组lncRNA NEAT1表达、DDIT4 mRNA表达均显著降低（均P < 0.05），miR-1287-5p 表达显著升高（P < 0.05）；而过表达lncRNA NEAT1则下调miR-1287-5p表达并上调DDIT4表达，呈现与敲低实验相反的调控效应；敲低lncRNA NEAT1后，克隆形成数、细胞增殖活性、细胞侵袭数均显著降低（均P < 0.05），细胞凋亡率显著升高（P < 0.05）；DDIT4、cyclin D1、MIEN1蛋白表达均显著降低（均P < 0.05），p53蛋白表达显著升高（P < 0.05）。进一步实验证实，anti-miR-1287-5p或OE-DDIT4均可减弱si-NEAT1对SKOV3细胞增殖和侵袭的抑制作用，同时减弱其对细胞凋亡的促进作用。lncRNA NEAT1靶向调控miR-1287-5p/DDIT4。结论：lncRNA NEAT1通过靶向调控miR-1287-5p/DDIT4轴促进SKOV3细胞增殖和侵袭，抑制细胞凋亡。

Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

BackgroundRumination can play a certain degree role of psychological adjustment in cancer patients. Previous studies have focused on studying the level of rumination in a single type of cancer patient， but there is a lack of comprehensive investigation and influencing factor research on rumination levels in different types of cancer patients. ObjectiveTo explore the level of rumination and its influencing factors among middle-advanced cancer inpatients， so as to provide certain guidance for targeted psychological care in clinical practice. MethodsFrom January 2021 to December 2022， a systematic sampling technique was used to recruit 346 patients with TNM stage III or above tumors hospitalized in Nuclear Industry 416 Hospital， Chengdu Sixth People's Hospital and the First People's Hospital of Yibin. All individuals were assessed using Perceived Social Support Scale （PSSS） and the Chinese version of Event-Related Ruminant Inventory （C-ERRI）， and Logistic regression analysis was utilized to identify the influencing factors of rumination. ResultsIn terms of C-ERRI， patients scored （15.59±5.61） on intrusive rumination and （14.59±5.43） on deliberate rumination. Education levels of junior high school/high school/vocational training school （OR=0.817， P<0.01） and junior college and above （OR=0.579， P<0.05） were the protective factors of intrusive rumination， whereas annual personal incomes of <10 000 yuan （OR=4.918， P<0.01） or 10 000~50 000 yuan （OR=2.076， P<0.01） and low （OR=6.882， P<0.01） or middle （OR=3.114， P<0.01） level of social support were the risk factors of intrusive rumination. For deliberate rumination， education levels of junior high school/high school/vocational training school （OR=0.574， P<0.01） and junior college and above （OR=0.449， P<0.05） were the protective factors， and low （OR=1.391， P<0.01） or middle （OR=1.161， P<0.05） levels of social support were the risk factors. ConclusionThe level of intrusive rumination of inpatients with middle-advanced cancer is related to education level， economic status and social support， furthermore， the level of deliberate rumination is related to the educational level and social support. ［Funded by Medical Research Project of Chengdu Health Commission （ number， 2020119）］

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.