Objective: To evaluate the performance of platelet efficacy score (PEscore) in predicting platelet transfusion efficacy in hematological patients. Methods: A total of 485 patients with hematological diseases, including 298 males (62.09±15.45 years) and 187 females (59.17±16.52 years) who received platelet transfusion from January 1, 2021 to December 31, 2024 were enrolled in this study. Clinical data of the patients such as diagnosis, gender, age, number of platelet transfusion, and platelet antibody data were analyzed to investigate the incidence and influencing factors of platelet transfusion refractoriness in hematological patients at our hospital. ROC curve was used to evaluate the performance of PEscore model in predicting platelet transfusion efficacy. The predictive performance of PEscore model was validated by calculating its sensitivity, specificity, and accuracy in 115 clinical cases. Results: The incidence of platelet transfusion refractoriness in 485 cases was 29.90% (145/485). Significant differences (P<0.05) were observed between the effective and ineffective platelet transfusion groups regarding the following factors: diagnosis: lymphoma [55.32% (26/47) vs 44.68% (21/47)], the number of previous platelet transfusions [≥25: 60.78% (31/51) vs 39.22% (20/51)], platelet antibody screening result [positive: 33.76% (53/157) vs 66.24% (104/157)], and platelet transfusion volume (×10 /L) [>6: 62.71% (74/118) vs 37.29% (44/118)]. The area under the ROC curve of PEscore was 0.876. The cut-off points and corresponding sensitivity and specificity were 19.90.59% and 69.44%, respectively. The results of clinical application showed that the sensitivity, specificity and accuracy of the PEscore model for predicting platelet transfusion were 87.50%, 93.41% and 92.17%, respectively. Conclusion: The incidence of platelet transfusion refractoriness in hematological patients is relatively high. PEscore prediction model has a good performance in predicting the effect of platelet transfusion, which can provide a reliable basis for predicting the effect of platelet transfusion in hematological patients before blood transfusion.

Objective Logistic regression model was used to analyze the risk factors of liver cancer in patients with hepatitis B virus-related cirrhosis. Methods A retrospective analysis was performed on 504 patients with hepatitis B cirrhosis who were treated in a hospital from April 2021 to April 2024. The occurrence of liver cancer was counted. The risk factors of liver cancer in patients with HBV-related cirrhosis were analyzed by logistic regression analysis. Results Among the 504 patients with hepatitis B cirrhosis, 101 patients developed liver cancer and 403 patients did not develop liver cancer, which were included in the liver cancer group (n=101) and the non-liver cancer group (n=403).. Among hepatitis B cirrhosis, the incidence rate of liver cancer was 20.04%. Compared with the non-liver cancer group, the proportion of patients with long-term drinking history, family history of liver cancer, history of diabetes mellitus, antiviral therapy, and HBV-DNA load>104 were higher in the liver cancer group (P<0.05). logistic regression analysis found that long-term drinking history (OR=3.077, 95%CI: 1.130-8.378, P=0.028), history of diabetes mellitus (OR=3.747, 95%CI: 1.765-7.954, P=0.001), no antiviral therapy (OR=3.466, 95%CI: 1.337-8.985, P=0.011) and HBV-DNA load>104 (OR=3.149, 95%CI: 1.353-7.328, P=0.008) could independently affect the occurrence of liver cancer in patients with hepatitis B cirrhosis. Conclusion According to logistic regression analysis, long-term drinking history, history of diabetes mellitus, no antiviral therapy, and HBV-DNA load>104 are risk factors for liver cancer in patients with HBV-related cirrhosis.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium ; Musa ; Phylogeny ; Trichodermin ; Hypocreales

Objective To investigate the expression and clinical relevance of heterogeneous nuclear ribonucleoproteins F(HNRNPF)in prostate cancer and its effect on the proliferation,migration and invasion of prostate cancer cells.Methods The expression and immune infiltration characteristics of HNRNPF in prostate cancer and its correlation with the clinicopathological characteristics of prostate cancer patients were analyzed using TCGA database and GEO database.The HNRNPF gene was silenced by RNA interference in prostate cancer cell PC-3 and DU145,then the changes in cell proliferation ability was detected by CCK-8,EdU and colony formation assays,and the changes in cell migration and invasion abilities were detected by Transwell and wound-healing assays.Results The expression of HNRNPF was significantly increased in prostate cancer compared with normal prostate tissue and significantly associated with T stage,Gleason score,prostate specific antigen and the infiltration level of multiple immune cells of prostate cancer patients.The prostate cancer patients with high expression of HNRNPF had shorter overall survival and disease-specific survival.HNRNPF silencing decreased the proliferation,migration,and invasion abilities of prostate cancer cells PC-3 and DU145.Conclusion HNRNPF is a gene that is highly expressed in prostate cancer,has significant clinical relevance,and can promote the proliferation,migration,and invasion of prostate cancer cells.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

BACKGROUND:The renin-angiotensin system plays a key role in the occurrence and development of hypertension,in which angiotensin(1-7)has antihypertensive effect and reversely regulates the adverse effects of angiotensin Ⅱ.Exercise rehabilitation therapy is an important non-pharmaceutical means to prevent and treat hypertension;however,whether angiotensin(1-7)and exercise have a synergistic effect is not yet clear. OBJECTIVE:To explore the effect of angiotensin(1-7)supplementation combined with exercise therapy on cardiac remodeling in rats with renal hypertension and to investigate the possible mechanism of angiotensin(1-7)and its receptor signal axis. METHODS:Sixty male Sprague-Dawley rats were selected,of which 12 rats were randomly selected as normotensive group and the remaining 48 rats were used to make animal models of renal hypertension using two-kidney one-clip method and were then randomly divided into hypertension control group,hypertension exercise group,angiotensin(1-7)group and combined treatment group.One week after successful modeling,different interventions were given(for a period of 6 weeks)as follows:the hypertension exercise group was subjected to a running training on an electric treadmill,the angiotensin(1-7)group was perfused with angiotensin(1-7)by implanting Alzet microosmotic pump subcutaneously on the back of the rats,and the combined treatment group was perfused with angiotensin(1-7)after running training,while the normotensive group and hypertension control group were caged quietly.At 48 hours after the last training session,the tail artery blood pressure was measured with a non-invasive sphygmomanometer;the heart structure and function were detected by echocardiography;the left ventricular myocardium was taken for histopathological observation by hematoxylin-eosin and Masson staining,and the cardiomyocyte cross-sectional area and collagen volume fraction were obtained by image analysis software as markers of myocardial hypertrophy and fibrosis,respectively;the content of angiotensin(1-7)in the heart was detected by high performance liquid chromatography;the mRNA expression of cardiac embryonic genes,atrial natriuretic peptide and β-myosin heavy chain,was detected by real-time fluorescence quantitative PCR;and the protein expression of cardiac Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was measured by western blot assay. RESULTS AND CONCLUSION:Compared with the normotensive group,blood pressure increased(P<0.05),cardiac function had no significant changes(P>0.05),cardiomyocyte cross-sectional area and collagen volume fraction increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was upregulated(P<0.05),angiotensin(1-7)content and protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was downregulated(P<0.05)in the hypertension control group.Compared with the hypertension control group,blood pressure decreased(P<0.05),cardiac function improved(P<0.05),collagen volume fraction decreased(P<0.05),cardiomyocyte cross-sectional area and angiotensin(1-7)content showed no significant changes(P>0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the hypertension exercise group;except for an increase in myocardial angiotensin(1-7)content(P<0.05),other parameters had no statistical significance(P>0.05)in the hypertension angiotensin(1-7)group.Compared with the hypertension exercise group,blood pressure decreased(P<0.05),cardiomyocyte cross-sectional area and cardiac function had no significant changes(P>0.05),collagen volume fraction decreased(P<0.05),angiotensin(1-7)content increased(P<0.05),mRNA expression of atrial natriuretic peptide and β-myosin heavy chain was downregulated(P<0.05),and the protein expression of Mas receptor,angiotensin Ⅱ type 2 receptor and endothelial nitric oxide synthase was upregulated(P<0.05)in the combined treatment group.To conclude,supplementation of angiotensin(1-7)alone cannot improve cardiac remodeling in rats with renal hypertension,but it can enhance the efficacy of exercise.The mechanism is related to the improvement of angiotensin(1-7)receptor deficiency and restoration of its signaling pathway function.

Diabetic kidney disease(DKD)is a high incidence microvascular complication caused by diabetes mellitus(DM).Persistent high glucose induces oxidative stress in the body.nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1)can play an anti-inflammatory and anti-oxidative role by inhibiting the accumulation of extracellular matrix in glomerular mesangium,inhibiting epithelial-mesenchymal transition in renal tubular epithelial cells,and inhibiting iron apoptosis,so as to improve renal function damage and delay the process of DKD.This article reviews the relationship between Nrf2/HO-1 pathway and DKD and the effect of traditional Chinese medicine active ingredients on DKD through Nrf2/HO-1 signaling pathway,in order to provide a basis for the development of new drugs.

During the occurrence and development of various heart diseases,continuous deterioration of myocardial fibrosis leads to remodeling and dysfunction of the cardiac structure.As a newly discovered mechanically sensitive ion channel,Piezo1 has opened up a new field of research on cellular mechanical transduction.Piezo1 combines a fine force transducer with Ca2+ influx and participates in the regulation of cellular mechanical transduction,thereby regulating cellular biological functions.Recent studies have shown that the biomechanical changes induced by myocardial injury regulate the expression of Piezo1 in cardiomyocytes and cause an imbalance in calcium homeostasis,which plays an important role in the positive feedback loop of myocardial fibrosis.This review summarizes the theoretical basis and related studies of Piezo1 in regulating cardiac fibrosis and suggests that the Piezo1 channel may become a new target for the treatment of cardiac fibrosis,thereby providing a new research horizon for the prevention and treatment of cardiac fibrosis.