The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

Objective To analyze the causes and compensation characteristics of medical damage disputes in Anhui Province in recent years,and provide reference suggestions for effectively controlling and reducing the incidence of medical errors and doctor-patient conflicts.Methods The 1 876 cases of medical damage disputes in Anhui Province from 2017 to 2022 were included in the judgment documents network,and their occurrence years and causes of disputes were analyzed.Results The number of medical malpractice cases did not decrease significantly,and the average amount of compensation continued to increase;the top three causes of disputes were improper treatment or surgery(54.6%),and the average first place of actual compensation was improper medication or adverse drug reactions,and in terms of hospital level,1 009 cases(53.8%)were concentrated in tertiary public hospitals,the average actual compensation amount of private hospitals ranked first;the top three departments were surgery(44.62%);the highest incidence of damage was death(40.2%),and the average compensation amount for first-class disability was the highest.Hospitals were mainly responsible for secondary responsibilities(38.7%).Conclusion The contradiction between doctors and patients is still serious,so it is necessary to promote the construction of tight medical association and medical community,guide the allocation of medical resources,pay attention to risk sharing and management optimization,and reduce the incidence of medical damage disputes.

Objective To explore the role of miR-204-3p in silicosis and to elucidate the mechanism by which it affects silicosis fibers by regulating silica dust-induced alveolar epithelial-mesenchymal transition(EMT)in rats.Methods Forty SD rats were divided randomly into 4 groups:Control,Silicosis,AAV-Control,and AAV-miR-204-3p groups.The pathology of lung tissue damage was detected by hematoxylin and eosin(HE)and Masson staining.Relative expression levels of miR-204-3p and EMT marker genes in lung tissues from rats in each group were analyzed by real-time fluorescence reverse transcription quantitative PCR(RT-qPCR),and protein expression levels of EMT-related markers in lung tissues were detected by Western blot.Results The alveolar structure was damaged,the lung septa showed interstitial fibrosis,and expression levels of mesenchymal markers were elevated in the Silicosis group compared with the Control group(P＜0.05,P＜0.01,P＜0.001).The alveolar structure was more complete,the EMT process was alleviated,fibrosis was improved,and mesenchymal marker expression was reduced in the AAV-miR-204-3p group compared with the AAV-Control group(P＜0.05,P＜0.01,P＜0.001).Conclusions Free silica dust induces EMT in rat lung tissue.Overexpression of miR-204-3p can attenuate the EMT process induced by free silica dust in rats,and may thus affect silicosis fibrosis.

Objective To analyze the research status,development trends and hotspots in the field of corticomuscular coherence(CMC).Methods Relevant literatures on CMC from 1999 to 2024 were retrieved from the Web of Science Core Collection.CiteSpace 6.3R1 was ued to evaluate publications across multiple dimensions,including publication volume,countries/regions,institutions,authors,cited journals,cited references and keywords.Research hotspots and fron-tier dynamics were identified through keyword co-occurrence,clustering and bursting.Results A total of 447 articles were included.The overall publication trend for CMC research showed a fluctuating up-ward trajectory,peaking in 2023.China led in publication volume but exhibited relatively low centrality and inter-national collaboration.Germany led the way in academic influence.Aalto University and the University of Lon-don served as academic hubs for CMC research.The most influential research team,led by Mathieu Bourgui-gnon,focused on the physiological mechanisms and motor control applications of CMC.The Journal of Physiolo-gy-London was identified as the most impactful journal in the CMC field.CMC research spaned from molecular mechanisms to system-level behavior,delving into the interdisciplinary nexus of neuroscience and motor science while gradually extending to foundational studies in psychology and biology.High-interest keywords included synchronization,motor cortex and precision grip task.Current research hotspots encompassed connectivity,reor-ganization and activation.Future research was predicted to focus on advancements in CMC technology,interven-tions for neurological disorders,brain-muscle interaction mechanisms and signal processing.Conclusion CMC research has rapidly progressed in recent years,becoming a pivotal direction in motor function assess-ment and neurorehabilitation.Future studies should focus on optimizing CMC analytical techniques to enhance their application in brain-computer interfaces and personalized rehabilitation.Additionally,interdisciplinary col-laboration and international exchange should be strengthened to improve research quality and global impact.

Objective To analyze the research status,development trends and hotspots in the field of corticomuscular coherence(CMC).Methods Relevant literatures on CMC from 1999 to 2024 were retrieved from the Web of Science Core Collection.CiteSpace 6.3R1 was ued to evaluate publications across multiple dimensions,including publication volume,countries/regions,institutions,authors,cited journals,cited references and keywords.Research hotspots and fron-tier dynamics were identified through keyword co-occurrence,clustering and bursting.Results A total of 447 articles were included.The overall publication trend for CMC research showed a fluctuating up-ward trajectory,peaking in 2023.China led in publication volume but exhibited relatively low centrality and inter-national collaboration.Germany led the way in academic influence.Aalto University and the University of Lon-don served as academic hubs for CMC research.The most influential research team,led by Mathieu Bourgui-gnon,focused on the physiological mechanisms and motor control applications of CMC.The Journal of Physiolo-gy-London was identified as the most impactful journal in the CMC field.CMC research spaned from molecular mechanisms to system-level behavior,delving into the interdisciplinary nexus of neuroscience and motor science while gradually extending to foundational studies in psychology and biology.High-interest keywords included synchronization,motor cortex and precision grip task.Current research hotspots encompassed connectivity,reor-ganization and activation.Future research was predicted to focus on advancements in CMC technology,interven-tions for neurological disorders,brain-muscle interaction mechanisms and signal processing.Conclusion CMC research has rapidly progressed in recent years,becoming a pivotal direction in motor function assess-ment and neurorehabilitation.Future studies should focus on optimizing CMC analytical techniques to enhance their application in brain-computer interfaces and personalized rehabilitation.Additionally,interdisciplinary col-laboration and international exchange should be strengthened to improve research quality and global impact.

Objective To explore the role of miR-204-3p in silicosis and to elucidate the mechanism by which it affects silicosis fibers by regulating silica dust-induced alveolar epithelial-mesenchymal transition(EMT)in rats.Methods Forty SD rats were divided randomly into 4 groups:Control,Silicosis,AAV-Control,and AAV-miR-204-3p groups.The pathology of lung tissue damage was detected by hematoxylin and eosin(HE)and Masson staining.Relative expression levels of miR-204-3p and EMT marker genes in lung tissues from rats in each group were analyzed by real-time fluorescence reverse transcription quantitative PCR(RT-qPCR),and protein expression levels of EMT-related markers in lung tissues were detected by Western blot.Results The alveolar structure was damaged,the lung septa showed interstitial fibrosis,and expression levels of mesenchymal markers were elevated in the Silicosis group compared with the Control group(P＜0.05,P＜0.01,P＜0.001).The alveolar structure was more complete,the EMT process was alleviated,fibrosis was improved,and mesenchymal marker expression was reduced in the AAV-miR-204-3p group compared with the AAV-Control group(P＜0.05,P＜0.01,P＜0.001).Conclusions Free silica dust induces EMT in rat lung tissue.Overexpression of miR-204-3p can attenuate the EMT process induced by free silica dust in rats,and may thus affect silicosis fibrosis.

Objective To analyze the causes and compensation characteristics of medical damage disputes in Anhui Province in recent years,and provide reference suggestions for effectively controlling and reducing the incidence of medical errors and doctor-patient conflicts.Methods The 1 876 cases of medical damage disputes in Anhui Province from 2017 to 2022 were included in the judgment documents network,and their occurrence years and causes of disputes were analyzed.Results The number of medical malpractice cases did not decrease significantly,and the average amount of compensation continued to increase;the top three causes of disputes were improper treatment or surgery(54.6%),and the average first place of actual compensation was improper medication or adverse drug reactions,and in terms of hospital level,1 009 cases(53.8%)were concentrated in tertiary public hospitals,the average actual compensation amount of private hospitals ranked first;the top three departments were surgery(44.62%);the highest incidence of damage was death(40.2%),and the average compensation amount for first-class disability was the highest.Hospitals were mainly responsible for secondary responsibilities(38.7%).Conclusion The contradiction between doctors and patients is still serious,so it is necessary to promote the construction of tight medical association and medical community,guide the allocation of medical resources,pay attention to risk sharing and management optimization,and reduce the incidence of medical damage disputes.

Background Long-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. Objective To observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. Methods Forty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL⁻¹) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Results The anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P<0.05), and the relative expression level of miR-204-3p in lung tissue of the miR-204-3p intervention group was increased (P＜0.05). The results of immunohistochemistry showed that compared with the control group, the expression levels of Fibronectin and Collagen I in lung tissue of the silicosis model group were increased (P＜0.05). Compared with the silicosis model group, the relative expression levels of Fibronectin and Collagen I in lung tissue of the rats in the miR-204-3p intervention group were significantly decreased (P<0.05). The results of RT-qPCR and Western blot showed that compared with the control group, the relative protein and gene expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of the silicosis model group increased (P＜0.05). Compared with the silicosis model group, the relative gene and protein expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in the miR-204-3p intervention group were decreased (P＜0.05). Conclusion Silica dust can cause lung fibrosis in rats, and overexpression of miR-204-3P in vivo can reduce silicosis fibrosis in rats caused by silica dust.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.