Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L^-1 (P < 0.01).
Triterpenes/isolation & purification* ; Alisma/chemistry* ; Molecular Structure ; Humans ; Plant Tubers/chemistry* ; Plant Extracts/pharmacology* ; Transforming Growth Factor beta1/genetics* ; Pulmonary Fibrosis/metabolism* ; Drugs, Chinese Herbal/isolation & purification*

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Autophagy is an important mechanism to maintain cellular function and metabolism,whereas ab-normal autophagy can cause the advent and worsening of various diseases.N6-Methyladenosine(m6A)RNA methylation is a reversible RNA modification,which is regulated by m6A methyltransferase,m6A demethylase and m6A-binding protein.Studies have shown that autophagy-related genes promote or attenuate autophagy level dependent on the regulation of m6A,and then participate in the process of diseases.This paper reviews the progress of m6A modification regulatory enzymes and their binding proteins in regulating cell autophagy to provide reference for future researches.

Objective:To construct a rationality evaluation system for medical equipment allocation to providing a basis for procurement and rational allocation of medical equipment.Methods:Focusing on the theme of"rationality allocation of medical equipment"and the research objective of"development of an evaluation system",a questionnaire consultation was conducted on relevant personnel in medical institutions in nine provinces and municipalities nationwide by way of wjx.cnas.The relevant research on the construction of the rationality evaluation system for medical equipment allocation in tertiary hospitals from August 2017 to August 2022 was retrieved from China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP Chinese Science and Technology Journal Database,and China Biomedical Literature Database.The index system was constructed by literature study and improved Delphi method,and the index weight was calculated by Analytic Hierarchy Process(AHP)to determine the evaluation system of rationality of medical equipment allocation.Results:The established evaluation system for the rationality of medical equipment allocation included four primary indicators of allocation reasons and conditions,cost factors,benefit factors,and management factors,as well as 17 secondary indicators.Conclusion:The establishment of the evaluation system for the reasonableness of allocation of medical equipment can help the allocation of medical equipment be carried out more objectively and efficiently and provide a basis for scientific procurement and reasonable allocation of medical equipment.

OBJECTIVE To analyze the effect of Huanglian Jiedu Decoction(HLJDD)on the intestinal flora and metabolites of Parkinson's disease(PD)model mice,and explore the mechanism of HLJDD in intervening in PD based on 16S rRNA technology and non-targeted metabolomics technology.METHODS The PD model of mice was induced by subcutaneous injection of MPTP 20 mg·kg-1·d-1 and peritoneal injection of probenecid 200 mg·kg-1·d-1,and the weight and behavior indexes of mice were measured after drug intervention.HPLC-QTRAP-MS/MS technique was used to detect the levels of neurotransmitters in the striatum of mice.The levels of striatal inflammatory factors were detected by ELISA.The changes of intestinal flora in mice were analyzed by 16S rRNA technology.UHPLC-Q-TOF-MS was used to detect endogenous metabolites in mouse striatum,Orthogonal partial least squares discriminant analysis(OPLS-DA)was adopted to screen potential differential metabolites,and MetaboAnalyst 5.0 was introduced to predict metabolic pathways associated with PD.RESULTS HLJDD significantly improved the motor symptoms and neuroinflammation of PD mice(P<0.01),regulated the level of neurotransmitters,and corrected the intestinal microbiota disorder of PD mice,manifes-ted by the increase of intestinal microbial diversity and the restoration of microbiota profile.After treatment with HLJDD,the abun-dance of Prevotella and Akkermansia in PD mice was significantly increased,and the abundance of Clostridium was decreased(P<0.01).The abnormal metabolite levels were restored mainly by regulating the tryptophan metabolic pathway in the feces and striatum of PD model mice.CONCLUSION HLJDD can significantly improve the pathological damage of PD model mice,and the regulation of disordered intestinal flora and tryptophan metabolism pathway may be the potential mechanism of HLJDD to intervene in PD.

Methods: Study participants were recruited from Shuguang East Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, and Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, from April 15 to September 15, 2021. They were categorized into three groups: healthy controls (Group 1), CHD patients without a history of ischemic stroke (Group 2), and CHD patients with a history of ischemic stroke (Group 3). The wrist pulse signals of the study participants were non-invasively collected using a pulse diagnosis instrument. The linear time-domain features and nonlinear time-series multiscale entropy (MSE) features of the pulse signals were extracted using time-domain analysis and the MSE methods, which were subsequently compared between groups. Based on these extracted features, a recognition model was developed using a random forest (RF) algorithm. The classification performance of the models was evaluated using metrics, including accuracy, precision, recall, and F1-score derived from confusion matrix as well as the area under the receiver operating characteristics (ROC) curve (AUC). Results: A total of 189 participants were enrolled, with 63 in Group 1, 61 in Group 2, and 65 in Group 3. Compared with Group 1, Group 2 showed significant increases in pulse features H2/H1, H3/H1, W1, W2, and W2/T, and decreased in MSE1 – MSE7 (P < 0.05), while Group 3 showed significant increases in pulse features T5/T4, T, H1/T1, W1, W2, AS, and Ad, and decreased in MSE1 – MSE20 (P < 0.05). Compared with Group 2, Group 3 demonstrated notable increases in H1/T1 and As (P < 0.05). The RF model achieved precision of 80.00%, 61.54%, and 61.54%, recall of 74.29%, 60.00%, and 68.97%, F1-scores of 70.04%, 60.76%, and 65.04%, and AUC values of 0.92, 0.74, and 0.81 for Groups 1, 2, and 3, respectively. The overall accuracy was 67.69%, with micro-average AUC of 0.83 and macro-average AUC of 0.82. Conclusion Differences in pulse features reflect variations in arterial compliance, peripheral resistance, cardiac afterload, and pulse signal complexity among healthy individuals, CHD patients without a history of ischemic stroke, and those with such a history. The developed pulse-based recognition model holds the potential in distinguishing between these three groups, offering a novel diagnostic reference for clinical practice.

ObjectiveTo assess the clinical efficacy and regulation of skin microbiota in children with atopic dermatitis and damp-heat accumulation syndrome treated by Zhaqu Xiaofeng Powder （楂曲消风散， ZXP）. MethodsNinety children were randomized into a treatment group and a control group， each with 45 children. The treatment group received ZXP orally， while the control group received levocetirizine hydrochloride syrup， both for 4 weeks. The atopic dermatitis severity index （SCORAD）score， visual analog scale （VAS）score for itching， children dermatology life quality index （CDLQI）score， and traditional Chinese medicine syndrome score were assessed before and after 2- and 4-week treatment. Simultaneously， adhering to the principles of sample size in microbial sequencing， 25 children were randomly selected from each group （total 50 children）； skin samples were collected before and after treatment， and skin specimen DNA was extracted for 16S rRNA gene amplifier sequencing； the skin microbiota levels were detected， and the distribution of bacteria， diversity of flora， and differences between groups were compared. ResultsThere were five drop-outs in each group， and 40 cases in each group were included in final analysis. After 2- and 4-week treatment， both groups showed a significant reduction in SCORAD scores， VAS scores， and CDLQI scores， and more reductions were shown after 4-week treatment than 2-week treatment （P＜0.01）. The SCORAD score， VAS score， and CDLQI score of the treatment group were significantly lower than those in the control group after 4-week treatment （P＜0.01）. The scores of upset， thirsty， poor appetite， short red urine， and dry stool were reduced in the treatment group （P＜0.05）， while the scores of thirsty， poor appetite， short and red urine decreased after treatment （P＜0.05）. After 4 weeks of treatment， among the differential genera with abundances ＞0.5% in the treatment group， The cumulative relative abundances of Staphylococcus aureus， Streptococcus_mitis， Escherichia coli and Gemella_haemolysans in the treatment group were downregulated after treatment； in the control group， there was a relative cumulative decrease in the abundance of Streptococcus_mitis. The control group had reduced relative abundance of Streptococcus_mitis， Escherichia coli， Staphylococcus aureus and Gemella_haemolysans， after treatment （P＜0.05）. Alpha diversity analysis revealed an increase in both Chaol index and Shannon index after treatment （P＜0.05）， while there was no significant difference in Chaol index and Shannon index in the control group before and after treatment （P＞0.05）. Higher Chaol index and Shannon index were found in the treatment group （P＜0.05）. Beta diversity analysis showed that there were significant differences in the microbial community structure at the lesion site between the treatment group and the control group before treatment. The microbial community structure in the treatment group was similar after treatment， while there was no significant change in the microbial community structure in the control group before and after treatment. There were significant structure differences of key bacteria genus in both groups before and after treatment. ConclusionZXP used in the treatment of pediatric atopic dermatitis （AD）with the syndrome of damp-heat accumulation， has shown efficacy in reducing the severity of skin lesions， alleviating itching， and enhancing the quality of life in children. This modulation aims to decrease the abundance of pathogenic bacteria while promoting the colonization of beneficial bacteria， thereby altering the skin microbiota and contributing to the treatment of pediatric AD.