Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

Liquid-liquid phase separation(LLPS)is the process where intracellular biomolecules rapidly form reversible high concentrations of liquid-phase condensates,resulting in the compartmentalization and the formation of intracellular membraneless organelles.LLPS is involved in various biological processes and pathologic processes,such as neurodegenerative diseases and cancers.Long noncoding RNAs(lncR-NAs)have been revealed to be closely related to phase separation.It has become a research hotspot in life science recently,because it provides new insight into the mechanism of lncRNAs.In this review,we focuses on the effect of lncRNA SLERT on the phase separation of nucleolar fibrillar center/dense fibrillar component(FC/DFC)by interacting with DDX21 protein as a molecular chaperone;LINC00657(NO-RAD)forms NP bodies with PUM proteins,which drives PUM protein liquid droplets and inhibits its ac-tivity,and promotes genomic stability;DilncRNA regulates DNA damage response small RNAs(DDR-NAs)and LLPS of p53 binding protein 1(53BP1)in response to DNA damage,and lncRNA LINP1 phase separation droplets bind to Ku protein to promote DNA damage repair;LncRNA SNHG9,MELTF-AS1 and MALR drive LATS1,YBX1 and ILF3 protein LLPS respectively to promote cancer,while GIR-GL and lncFASA act as tumor suppressor genes in cancer development through regulating the phase sepa-ration of CAPRIN1 and PRDX1 respectively;LncRNA XIST drives X chromosome inactivation by LLPS.In a word,we summarize the latest research progress about the functional roles of lncRNAs in FC/DFC nucleolus,genomic stability and DNA damage and repair,cancer and X-chromosome inactivation through regulating LLPS.This paper shows that lncRNAs can participate in multiple pathophysiological processes by regulating LLPS,which is expected to provide a new direction for the treatment of LLPS-mediated diseases.

Objective:To assess the feasibility and efficacy of transperineal laser ablation(TPLA)with single laser fiber in treating benign prostatic obstruction(BPO).Methods:From April 2021 to March 2024,a total of 13 BPO patients were selected from Beijing Friendship Hospital.TPLA was performed using a single laser fiber,which was guided by transrectal biplane ultrasound.The single laser fiber was used to undergo TPLA under the guidance of trans-rectal dual-plane ultrasound.The intraoperative time,ablation time,energy consumption,indwelling time of catheter,and complications were observed.The postoperative 6 months was chosen as the cut-off point of follow-up,and the pre and postoperative changes of international prostate symptom score(IPSS),quality of life index(QoL),prostate volume(PV),residual urine volume(RUV)and the maximum urine flow rate(Qmax)were compared.Results:All 13 patients successfully underwent TPLA with single laser fiber.The average operation time was(55.1±18.3)min,and the average ablation time was(16.3±1.7)min,and average energy consumption was(3951.6±459.7)J,and the median value of indwelling time of catheter was 7(7,10)days.The number of postoperative complication was 2 cases,and both them belonged to Clavien-Dindo grade II complication.At the postoperative 6th month,the IPSS,QoL,PV,Qmax and RUV of all patients were improved,all of which were better than preoperative these indicators,and the differences were significant(t=12.102,-3.228,-3.181,-2.581,-2.936,P<0.05).Conclusion:The application of single laser fiber in conducting TPLA operation is feasibility at technical aspect,and it can achieve the therapeutic goals of improving patients'symptoms and enhancing their quality of life.Although its operational time is slightly longer than that of using multiple fibers simultaneously,it can effectively reduce the cost of expenditure for consumables.

Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases