The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapa-mycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.

Objective:To evaluate the safety and efficacy of combined inflatable mediastinoscopy with laparoscopy guided by the concept of “reduced field and port” during esophagectomy for esophageal cancer.Methods:This is a retrospective cohort study. The clinical data of 497 patients with esophageal squamous cell carcinoma who underwent minimally invasive esophagectomy at the Center of Minimally Invasive Thoracic Surgery, the Second Affiliated Hospital of Naval Medical University, between January 2017 and December 2024 were retrospectively analyzed. There were 416 male and 81 female patients, with an age of (68.3±8.0) years (range: 44 to 89 years). Patients were divided into the traditional video-assisted thoracoscopic surgery group (Group A, n=354) and the combined inflatable mediastinoscopy with laparoscopic surgery group(Group B, n=143) based on the surgical approach. Furthermore, Group B was subdivided into the multiport laparoscopic group (Group B1, n=81) and the single-incision laparoscopic surgery plus one port group (Group B2, n=62). Perioperative indicators and postoperative survival differences were compared between the groups. Inter-group comparisons were performed using the independent sample t-test, χ2 test, or Fisher′s exact probability test. Survival curves were plotted using the Kaplan-Meier method, and the Log-rank test was used to analyze the survival differences between groups. Results:Compared with Group A, Group B demonstrated a significantly shorter operative time ((181.8±11.4) minutes vs. (196.7±8.1)minutes, t=16.09, P<0.01), a lower incidence of postoperative pulmonary complications (8.4% (12/143) vs. 17.8% (63/354), χ2=6.27, P=0.012), lower perioperative mortality (0 vs. 3.1%(11/354), P=0.039), and a shorter postoperative hospital stay ((16.2±2.2)days vs. (18.9±4.1)days, t=8.56, P<0.01). There was no significant difference in the anastomotic leak rate, number of lymph nodes dissected, or intraoperative blood loss between the two groups (all P>0.05). Overall survival time and recurrence-free survival time showed no significant difference between the two groups (all P>0.05). Subgroup analysis revealed no significant differences in perioperative indicators or postoperative complication rates between Group B1 and Group B2. Conclusions:Compared with traditional thoracoscopic combined with laparoscopic surgery, inflatable mediastinoscopy offered advantages in terms of lower postoperative pulmonary complication rates, shorter operative time, reduced postoperative hospital stay, and lower perioperative mortality. The “reduced field and port” concept could further minimize surgical trauma during the transmediastinal approach for esophagectomy while ensuring surgical safety and efficacy.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective To evaluate the modeling characteristics and predictive performance of models for predicting post-stroke neurological deterioration(ND)published in existing literatures.Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidance for scoping reviews,a comprehensive search was conducted in PubMed,CINAHL,Cochrane Library,Embase,Web of Science,Scopus,CNKI,Wanfang Data,and VIP databases from inception to December 15,2024.The search strategy combined Medical Subject Headings(MeSH)and free-text terms,with key words including"Stroke""Ischemic Stroke""Neurological Deterioration""Nomograms""Risk Prediction""Predictive Models""卒中""脑梗死""脑出血""神经功能恶化"and"预测模型".Base on the data extraction checklist and critical appraisal,data extraction covered three domains:(1)basic characteristics,including author,publication year,country,study design(retrospective,prospective,registry-based),sample source(single-center,multicenter),stroke subtypes(acute ischemic stroke[AIS]-conservative therapy,AIS-intravenous thrombolysis[IVT],AIS-endovascular therapy[EVT],intracerebral hemorrhage[ICH]),ND time windows(acute[≤72 h],subacute[≤ 7 d],long-term[≤90 d]),and outcome types(single/composite endpoints);(2)model evaluation metrics,including missing data handling(complete-case analysis,multiple imputation),model development methodologies(multivariate Logistic regression,least absolute shrinkage and selection operator regression,machine learning),presentation formats(nomograms,web calculators,risk prediction tool),discrimination(area under the curve,C-index),calibration(Hosmer-Lemeshow test,calibration curve and slope),clinical utility(decision curve analysis[DCA],global metrics Brier score,R2,AIC),sample size(training set,internal validation set,external validation set),sample size requirements(events per variable[EPV]≥10 to mitigate overfitting),and validation(internal/external);(3)predictor features,including selection strategies(prior knowledge-driven,univariate analysis),quantity,and attributes(demographics,medical history,physical examination,treatment intervention information,imaging/laboratory indicators).Predictive models that meet exclusion criteria from prior literature were analyzed by their discrimination,calibration,clinical utility and global metrics.Forest plots were utilized to visualize discrimination(evaluated via difference in area under the curve)of the extracted models.The prediction model risk of bias assessment tool(PROBAST)was applied to assess bias risk and clinical applicability.Occurrence frequencies of the post-stroke neurological deterioration predictors were ranked and the top 6 high-frequency predictors were extracted.Results(1)Among 3 728 screened studies,25 were included based on the inclusion and exclusion criteria.(2)Basic characteristics:retrospective(72％[18/25])and single-center(64％[16/25])designs dominated.With most models targeted on AIS(92％[23/25]),and the rest(8％[2/25])on ICH.ND was primarily defined by neurological scale changes(60％[15/25];e.g.,National Institutes of Health stroke scale[NIHSS]score increase or Glasgow coma scale[GCS]score decrease),with time windows categorized as acute(36％[9/25]),subacute(48％[12/25]),or long-term(16％[4/25]).(3)Model evaluation:multivariate Logistic regression(96％[24/25])and nomograms(88％[22/25])were predominant.Only 24％(6/25)explicitly addressed missing data handling methods,and 52％(13/25)with EPV≥10.The median area under the curve was 0.865(range:0.650-0.981).44％(11/25)of the studies reported calibration curves,and 4％(1/25)reported calibration slopes.All studies utilized DCA to validate their clinical applicability,84％(21/25)of the studies conducted internal validation,while only 32％(8/25)conducted external validation.PROBAST evaluation revealed low overall bias risk in 8％(2/25;no error across participant,predictor,outcome,or analysis domains)and low clinical applicability risk in 44％(11/25;alignment with target populations,accessible predictors,and clinically relevant outcomes)of the studies.(4)Predictors:64％(16/25)of the predictor were screened predominantly through the prior knowledge-driven based strategy.The top 6 high-frequency predictors are NIHSS score(64％[16/25]),age(36％[9/25]),blood glucose/diabetes(36％[9/25]),blood pressure/hypertension(32％[8/25]),the Alberta stroke program early CT score(20％[5/25]),and neutrophil-to-lymphocyte ratio(20％[5/25]).AIS-ND predictors emphasized readily available metrics,such as NIHSS(65％[15/23]),age(35％[8/23]),while ICH-ND primarily relied on imaging markers(e.g.,baseline hematoma volume[2/2],location[1/2]).Conclusion Current post-stroke ND predictive models demonstrate satisfactory performance on discrimination and multimodal integration,but their practical application are hindered by insufficient calibration quantification,high bias risk,and limited clinical translatability.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.