Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

In recent years, with the continuous advancement of related research, the clinical value of clot waveform analysis (CWA) in the diagnosis and management of thrombotic diseases has become increasingly prominent. As a dynamic coagulation monitoring technology based on optical principles, CWA overcomes the limitations of traditional coagulation tests (e.g., APTT, PT), which rely on single time-point parameters, in identifying hypercoagulable states, predicting thrombotic risk, and monitoring anticoagulant efficacy. By analyzing the kinetic profiles of the coagulation cascade, CWA provides multidimensional insights. This article elucidates the theoretical basis and principles of CWA, systematically reviews its applications in arterial/venous thrombosis, other hypercoagulability-related disorders, and anticoagulation therapy monitoring, and synthesizes recent advances of CWA for thrombotic diseases. Specifically, multiple studies demonstrate that CWA-APTT parameters (e.g., peak height Min1, Min2, Delta) can sensitively detect hypercoagulability. Combining CWA with the Padua score significantly enhances the predictive power for venous thromboembolism (VTE) risk assessment. CWA shows clinical utility in evaluating hypercoagulability in patients with acute myocardial infarction (AMI) and acute cerebral infarction (ACI), where parameters such as Min1, Min2, and Max2 exhibit greater sensitivity than conventional APTT. These metrics may predict AMI complications and guide clinical management. Additionally, CWA demonstrates value in diverse scenarios including pregnancy, inflammation-associated hypercoagulability (e.g., COVID-19, Kawasaki disease), and rare thrombotic conditions (e.g., chronic spontaneous urticaria). Beyond diagnostic and risk-stratification advantages, CWA serves as a novel tool for personalized anticoagulation monitoring. Its derivative technology, clot-fibrinolysis waveform analysis (CFWA), extends applications to fibrinolysis assessment—aiding in identifying coagulation status in deep vein thrombosis (DVT) patients, tracking coagulation/fibrinolysis dynamics in COVID-19, and evaluating efficacy of anticoagulant/antifibrinolytic therapies. Nevertheless, despite its unique strengths, challenges such as device dependency, insufficient standardization, and heterogeneity in parameter interpretation hinder widespread clinical adoption, necessitating further investigation. Future directions include establishing multidimensional thrombotic risk assessment systems integrating CWA and developing AI-powered automated CWA analysis platforms to enhance clinical accessibility.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Objective:To systematically evaluate the effectiveness and feasibility of aerobic exercise intervention in schizophrenia patients.Methods:Randomized controlled trials on exercise interventions for patients with schizophrenia were searched in eight databases from built up to March 2023, including China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP), WanFang Data, China Biomedical Literature Database, PubMed, Cochrane Library, EMBASE and Web of Science. The positive and negative symptom scale (PANSS) and its sub-scales were used as primary outcome indicators, and the negative symptom scale (SANS) and body mass index (BMI) were used as secondary indicators, and Meta-analysis was performed using R 4.1.0 and Stata 14.0.Results:Forty-seven studies including 3 139 patients with schizophrenia were included. Results of a network Meta-analysis based on 24 studies showed that aerobic exercise may be the most effective measure for reducing total PANSS scores in patients with schizophrenia. Compared to conventional treatment, combining aerobic exercise intervention improved patients' PANSS total score (MD= -5.09, 95% CI: -5.90~-4.28), SANS (MD= -12.17, 95% CI: -14.25~-10.10), and BMI (MD=-1.59, 95% CI: -1.93~-1.25). Meanwhile, subgroup analysis showed that 2 months of intervention was more appropriate (MD=-6.12, 95% CI: -7.22~-5.02) and the weekly total exercise time for 140-260 min was more appropriate (MD=-8.59, 95% CI: -12.93~-4.25) in terms of total PANSS score. The adherence rates between the trial and control groups showed no significant difference between the aerobic exercise intervention combined with conventional treatment and conventional treatment alone( P>0.05). Conclusion:Aerobic exercise intervention is an effective measure to relieve the symptoms of schizophrenia patients and has good compliance among inpatients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To study the stability and morphological changes of the convexity sulci in normal fetuses between 20 and 32 weeks, and to explore the simplified grade for evaluating the convexity sulci development and analyzing its clinical significance.Methods:This study was a cross-sectional analysis. A total of 551 cases of normal singleton pregnancies between 20 and 32 weeks of gestation were retrospectively collected, who underwent routine ultrasound examinations at Shenzhen Maternity and Child Healthcare Hospital from September 2019 to June 2022. The display of the far-field convexity sulci on the transcalvarial axial plane was observed as 0 for not displayed and 1 for displayed.Further, based on the morphology and number of convexity sulci, they were classified into five grades: no sulcus displayed (grade 0), one sulcus (grade 1), two sulci (grade 2), three sulci (grade 3), and four or more sulci (grade 4). The gestational age at examination and pregnancy outcomes were recorded. The distribution characteristics of gestational weeks for each grade of the convexity sulci were analyzed, and the gestational week distribution of the left and right convexity sulci was compared to analyze bilateral symmetry. The Weighted Kappa coefficient was used to analyze inter-observer and intra-observer consistency, and curve regression analysis was employed to establish a model for predicting grade based on gestational weeks.Results:Before 25 weeks of gestation, the convexity of the fetal cranial vertex was completely smooth.The central sulcus consistently appeared after 26 weeks, while the superior frontal sulcus, intraparietal sulcus, postcentral sulcus, and precentral sulcus consistently appeared between 28 and 31 weeks. Among these, the superior frontal sulcus had a lower display rate before 29 weeks. By 32 weeks, all convexity sulci of the cranial vertex should be visible. Three hundred and eleven fetuses were graded for the left, and 240 fetuses were graded for the right. The developmental grade of the convexity sulci increased from Grade 0 to Grade 4 as the gestational age progressed. Grade 0 appeared between 20-26 weeks, grade 1 between 25-28 weeks, grade 2 between 26-28 weeks, grade 3 between 27-30 weeks, and grade 4 between 27-32 weeks. The distribution of grade did not differ significantly between the left and right sides of grade 0, 1, 3 and 4 (all P>0.05), while there was a significant difference in the distribution of gestational age between the convexity sulci of grade 2 ( P<0.05). The Weighted Kappa coefficients for intra-observer and inter-observer consistency were 0.94 and 0.86, respectively, indicating strong consistency. Conclusions:The simplified grade for assessing the development of convexity sulci in normal fetuses on the transcalvarial axial plane via prenatal ultrasound can provide a preliminary evaluation of the maturation of convexity sulci in fetuses between 20 and 32 weeks of gestation.

Twelve compounds were isolated from Liquidambaris Resina by silica gel column chromatography and thin layer chromatography. Their structures were identified on the basis of spectral data, electron capture detector data, and physicochemical properties as(2'R, 3'R)-2',3'-dihydroxy-hydrocinnamyl-(E)-cinnamate(1),(E)-cinnamyl-(E)-cinnamate(2), cinnamic acid(3), 28-norlup-20(29)-en-3-one-17β-hydroperoxide(4), erythrodiol(5), 13β,28-epoxy-30-hydroxyolean-1-en-3-one(6),(3β)-olean-12-ene-3,23-diol(7), 2α,3α-dihydroxy-olean-12-en-28-oic acid(8), 28-hydroxyolean-12-en-3-one(9), 3-epi-oleanolic acid(10), 3-oxo-oleanolic acid(11), and hederagenin(12). Compound 1 was a new cinnamic acid ester derivative and compounds 2-4,6-8, and 12 were isolated from Liquidambaris Resina for the first time. Compounds 4, 5, 10, and 12 exerted inhibitory effects on the proliferation of human umbilical vein endothelial cells(HUVEC) with the IC_(50) values of(17.43±2.17),(35.32±0.61),(27.50±0.80), and(46.30±0.30) μmol·L~(-1), respectively.
Humans ; Oleanolic Acid ; Endothelial Cells ; Esters ; Cinnamates ; Triterpenes/chemistry* ; Molecular Structure

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.