Objective:To construct a temperature-sensitive hydrogel (PF-CA@AS-IV hydrogel) composed of Pluronic F-127 (PF-127)/calcium alginate (CA) loaded with astragaloside IV (AS-IV), and to explore its repair effect and potential mechanism on diabetic skin ulcers (DSU).Methods:The PF-CA@AS-IV hydrogel loaded with AS-IV and gelling at 37 ℃ was prepared. Its temperature sensitivity, rheological properties, and morphology were characterized. A rat model of DSU was established, and the rats were randomly divided into blank control group, model group, AS-IV spray group, PF-CA hydrogel group, and PF-CA@AS-IV hydrogel group ( n=5 each). After 21 days of intervention, the wound healing rate of each group was evaluated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of granulation tissue, and immunohistochemistry was applied to detect the expression level of CD34, a marker of new blood vessels. Results:Rheological analysis showed that the storage modulus (G′) of PF-CA@AS-IV hydrogel began to exceed the loss modulus (G″) at 33 ℃, and a stable three-dimensional network structure was formed at 37 ℃. Scanning electron microscopy confirmed its loose and porous microstructure. Animal experiment results indicated that compared with the blank control group, the model group had a significantly lower wound healing rate, massive infiltration of inflammatory cells, and fewer new capillaries and CD34 expression (all P<0.05). Compared with the model group, each treatment group can promote wound healing, reduce inflammatory infiltration and increase the positive expression of CD34 to varying degrees (all P<0.05), and the curative effect of PF-CA@AS-IV hydrogel group is the most significant, which is better than that of AS-IV spray group and PF-CA hydrogel group (all P<0.05). Conclusions:PF-CA@AS-IV hydrogel can effectively regulate inflammatory response and promote angiogenesis through sustained release of AS-IV, thereby accelerating DSU healing, and has good translational potential in the field of chronic wound repair.

The spatio-temporal heterogeneity of breast cell subsets forms the fundamental biological basis for physiological development and pathological progression, including tumorigenesis; however, its complex regulatory mechanisms are not yet fully elucidated. With its high-resolution capabilities, single-cell RNA sequencing (scRNA-seq) technology offers a powerful tool for dissecting this cellular heterogeneity. This technology enables the construction of high-precision breast cell atlases, the accurate identification of distinct cell subsets, and the reconstruction of differentiation trajectories from stem/progenitor cells to functional epithelial cells. By resolving the transcriptional regulatory networks that govern cell fate determination, intercellular communication patterns, and dynamic microenvironmental interactions, scRNA-seq has unveiled the molecular foundations of breast development and provided new perspectives on the pathogenesis of related diseases such as breast cancer and macromastia. Furthermore, scRNA-seq demonstrates significant potential for discovering early molecular markers of disease, deciphering tumor heterogeneity, and elucidating mechanisms of therapeutic resistance. The continued application of scRNA-seq for dissecting breast cell heterogeneity, combined with its integration with multi-modal data such as spatial omics, promises to provide critical evidence and new insights for revealing the molecular mechanisms of breast development-related diseases and for formulating precision therapeutic strategies.
Humans ; Single-Cell Analysis/methods* ; Female ; Breast Neoplasms/pathology* ; Sequence Analysis, RNA/methods* ; Breast/cytology*

Objective:To construct a temperature-sensitive hydrogel (PF-CA@AS-IV hydrogel) composed of Pluronic F-127 (PF-127)/calcium alginate (CA) loaded with astragaloside IV (AS-IV), and to explore its repair effect and potential mechanism on diabetic skin ulcers (DSU).Methods:The PF-CA@AS-IV hydrogel loaded with AS-IV and gelling at 37 ℃ was prepared. Its temperature sensitivity, rheological properties, and morphology were characterized. A rat model of DSU was established, and the rats were randomly divided into blank control group, model group, AS-IV spray group, PF-CA hydrogel group, and PF-CA@AS-IV hydrogel group ( n=5 each). After 21 days of intervention, the wound healing rate of each group was evaluated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of granulation tissue, and immunohistochemistry was applied to detect the expression level of CD34, a marker of new blood vessels. Results:Rheological analysis showed that the storage modulus (G′) of PF-CA@AS-IV hydrogel began to exceed the loss modulus (G″) at 33 ℃, and a stable three-dimensional network structure was formed at 37 ℃. Scanning electron microscopy confirmed its loose and porous microstructure. Animal experiment results indicated that compared with the blank control group, the model group had a significantly lower wound healing rate, massive infiltration of inflammatory cells, and fewer new capillaries and CD34 expression (all P<0.05). Compared with the model group, each treatment group can promote wound healing, reduce inflammatory infiltration and increase the positive expression of CD34 to varying degrees (all P<0.05), and the curative effect of PF-CA@AS-IV hydrogel group is the most significant, which is better than that of AS-IV spray group and PF-CA hydrogel group (all P<0.05). Conclusions:PF-CA@AS-IV hydrogel can effectively regulate inflammatory response and promote angiogenesis through sustained release of AS-IV, thereby accelerating DSU healing, and has good translational potential in the field of chronic wound repair.

Objective:This study aimed to investigate the clinical features and prognosis of Pseudomonas aeruginosa infection in patients with hematologic malignancies.Methods:This study retrospectively analyzed the clinical data of 197 patients with hematologic malignancies complicated with P. aeruginosa infection who were hospitalized in the Department of Hematology from January 01, 2019, to December 31, 2021. Patients were categorized into a susceptible group (CSPA infection group) and a drug-resistant group (CRPA infection group) based on their sensitivity to carbapenems, comparing the differences in clinical features between the two groups, and analyzing the risk factors and prognosis of CRPA infection.Results:Logistic regression analysis revealed that hospitalization days of >50 days ( P=0.010, OR=3.581, 95% CI 1.356-9.457), history of antibiotic exposure ( P=0.008, OR=4.394, 95% CI 1.358-6.238), more than two courses of chemotherapy before infection ( P=0.006, OR=2.911, 95% CI 1.358-6.238) were independent risk factors for developing CRPA. The mortality rates were 12.8% (18/140) and 28.1% (16/57) in patients with CRPA and CSPA, respectively ( P=0.010). Logistic regression analysis revealed that bloodstream infection (BSI) ( P=0.039, OR=5.286, 95% CI 1.091-25.621) was an independent risk factor for hematologic malignancies and death from CRPA infection. Conclusion:Hospitalization for >50 days, history of antibiotic exposure, and >2 courses of chemotherapy before infection were independent risk factors for CRPA infection. Hematologic malignancies with CRPA infection had a high mortality rate, of which BSI was an independent risk factor for 30-day mortality from hematologic malignancies with CRPA infection.

Objective:This study aimed to investigate the clinical value of glucocorticoids in patients with neutropenic severe pneumonia at moderate to high risk according to the Pneumonia Severity Index (PSI) in patients with hematologic diseases.Methods:Clinical data were collected from 534 patients at the Fujian Medical University Union Hospital from October 2016 to December 2018. We evaluated the changes in inflammatory cytokines, treatment failure, in-hospital mortality, and other outcomes, adjusting for potential confounders through propensity score matching.Results:Patients were categorized into glucocorticoids ( n=176) and control ( n=358) groups. The glucocorticoid group demonstrated higher levels of C-reactive protein, procalcitonin, and interleukin-6, alongside higher PSI scores. The differences in comorbidities diminished, except for inflammatory cytokine levels, with a notable reduction in inflammatory cytokines observed in the glucocorticoid group, after matching 125 pairs based on propensity scores. Late treatment failure was more prevalent in the glucocorticoid group (39.2% vs 24.8%, P=0.015), but this was primarily caused by radiographic progression. The incidences of respiratory failure, mechanical ventilation, and septic shock were similar between the groups. Logistic regression analyses revealed that glucocorticoids reduced the risk of treatment failure ( OR=0.367, 95% CI 0.165-0.818, P=0.014). The 30-day in-hospital mortality rates were comparable (8.0% in glucocorticoids vs 7.2% in controls, P=0.811), with indications that glucocorticoids may exert a protective effect on mortality. The PSI score was determined as the sole independent risk factor for 30-day in-hospital mortality ( OR=1.077, 95% CI 1.032-1.123, P=0.001). No evidence indicated that glucocorticoids increased the incidence of hyperglycemia, gastrointestinal bleeding, or 30-day infection recurrence. Conclusion:Glucocorticoids reduce inflammatory cytokine levels and are potentially related to decreased treatment failure and mortality in patients with neutropenic pneumonia classified as PSI Ⅳ and Ⅴ among hematological patients.

Objective:To investigate the effects and mechanism of metformin on the wound healing of full-thickness skin defects in diabetic rats.Methods:This study was an experimental study. Eighteen 8-week-old male Sprague Dawley rats were divided into control group, diabetes group, and diabetes+metformin group according to complete random grouping method, with 6 rats in each group. The latter two groups of rats were used to create diabetic models, and then four circular full-thickness skin defect wounds with a diameter of 5 mm were made on the back of 18 rats. Metformin F-127 hydrogel was applied only to the wounds of rats in diabetes+metformin group. The wound healing status on post injury day (POD) 7 and 13 was observed and the wound healing rate was calculated. The wound tissue on POD 7 and 13 was collected for hematoxylin-eosin staining to measure the length of re-epithelialized epidermis and calculate the change rates in diameters of epidermal and dermal wounds, for immunohistochemical staining to detect the relative expressions of keratin 10 and proliferating cell nuclear antigen (PCNA), and for Western blotting to detect the protein expressions of keratin 10 and PCNA. The sample size in all the above experiments was 8 except that in the last experiment was 3. The correlations between the relative expressions of keratin 10 and PCNA in wound tissue in three groups of rats and their wound healing rates, and the correlation between the relative expressions of keratin 10 and PCNA in wound tissue were analyzed.Results:On POD 7, the wound healing rates of rats in diabetes group and diabetes+metformin group were 81.48% (77.89%, 85.53%) and 93.04% (92.51%, 94.24%), which were significantly lower than 100% (97.17%, 100%) in control group (with Z values of 2.37 and -3.36, respectively, P<0.05); the wound healing rate of rats in diabetes+metformin group was significantly higher than that in diabetes group ( Z=3.45, P<0.05). On POD 13, the wound healing rates of rats in control group and diabetes+metformin group were both 100% (100%, 100%), which were significantly higher than 94.47% (90.68%, 99.82%) in diabetes group (with Z values of 2.90 and -2.90, respectively, P<0.05). On POD 7, the change rates in epidermal wound diameter of rats in control group and diabetes+metformin group were significantly higher than that in diabetes group (with Z values of 3.36 and -2.74, respectively, P<0.05). The change rates in dermal wound diameter of rats in the three groups were similar on POD 7 and 13 ( P>0.05). The lengths of re-epithelialized epidermis of rats in control group and diabetes+metformin group on POD 13 were significantly longer than that in diabetes group (with Z values of 3.34 and -2.64, respectively, P<0.05). The relative expressions of keratin 10 in wound tissue of rats in diabetes group on POD 7 and 13 were significantly higher than those in control group (with Z values of -3.36 and -3.26, respectively, P<0.05) and diabetes+metformin group (with Z values of 3.36 and 3.15, respectively, P<0.05), and the relative expression of keratin 10 in wound tissue of rats in diabetes+metformin group on POD 7 was significantly lower than that in control group ( Z=3.05, P<0.05); the relative expressions of PCNA in wound tissue of rats in diabetes group on POD 7 and 13 were significantly lower than those in control group (with both Z values of 3.36, P<0.05) and diabetes+metformin group (with both Z values of -3.36, P<0.05). The protein expressions of keratin 10 in wound tissue of rats in control group and diabetes+metformin group on POD 7 as well as that in diabetes+metformin group on POD 13 were significantly lower than those in diabetes group ( P<0.05), and the protein expressions of PCNA in wound tissue of rats in control group and diabetes+metformin group on POD 7 were significantly higher than that in diabetes group ( P<0.05). There was a significant positive correlation between the relative expression of keratin 10 in wound tissue and the wound healing rate in control group and diabetes+metformin group of rats (with r values of 0.78 and 0.71, respectively, P<0.05), there was a significant negative correlation between the relative expression of PCNA in wound tissue and the wound healing rate in diabetes+metformin group of rats ( r=-0.60, P<0.05), and there was a significant negative correlation between the relative expressions of PCNA and keratin 10 in wound tissue of rats in diabetes group and diabetes+metformin group (with r values of -0.41 and -0.49, respectively, P<0.05). Conclusions:The diabetic rats with full-thickness skin defect wound exhibit delayed healing, accompanied by up-regulation of keratin 10 and down-regulation of PCNA in keratinocytes in the wound tissue. Metformin can promote wound healing in diabetic rats with full-thickness skin defects by down-regulating keratin 10 expression and up-regulating PCNA expression in keratinocytes in the wound tissue, and the wound healing rate was positively correlated with the expression of keratin 10 and negatively correlated with the expression of PCNA.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:This study aimed to investigate the clinical features and prognosis of Pseudomonas aeruginosa infection in patients with hematologic malignancies.Methods:This study retrospectively analyzed the clinical data of 197 patients with hematologic malignancies complicated with P. aeruginosa infection who were hospitalized in the Department of Hematology from January 01, 2019, to December 31, 2021. Patients were categorized into a susceptible group (CSPA infection group) and a drug-resistant group (CRPA infection group) based on their sensitivity to carbapenems, comparing the differences in clinical features between the two groups, and analyzing the risk factors and prognosis of CRPA infection.Results:Logistic regression analysis revealed that hospitalization days of >50 days ( P=0.010, OR=3.581, 95% CI 1.356-9.457), history of antibiotic exposure ( P=0.008, OR=4.394, 95% CI 1.358-6.238), more than two courses of chemotherapy before infection ( P=0.006, OR=2.911, 95% CI 1.358-6.238) were independent risk factors for developing CRPA. The mortality rates were 12.8% (18/140) and 28.1% (16/57) in patients with CRPA and CSPA, respectively ( P=0.010). Logistic regression analysis revealed that bloodstream infection (BSI) ( P=0.039, OR=5.286, 95% CI 1.091-25.621) was an independent risk factor for hematologic malignancies and death from CRPA infection. Conclusion:Hospitalization for >50 days, history of antibiotic exposure, and >2 courses of chemotherapy before infection were independent risk factors for CRPA infection. Hematologic malignancies with CRPA infection had a high mortality rate, of which BSI was an independent risk factor for 30-day mortality from hematologic malignancies with CRPA infection.

Objective:This study aimed to investigate the clinical value of glucocorticoids in patients with neutropenic severe pneumonia at moderate to high risk according to the Pneumonia Severity Index (PSI) in patients with hematologic diseases.Methods:Clinical data were collected from 534 patients at the Fujian Medical University Union Hospital from October 2016 to December 2018. We evaluated the changes in inflammatory cytokines, treatment failure, in-hospital mortality, and other outcomes, adjusting for potential confounders through propensity score matching.Results:Patients were categorized into glucocorticoids ( n=176) and control ( n=358) groups. The glucocorticoid group demonstrated higher levels of C-reactive protein, procalcitonin, and interleukin-6, alongside higher PSI scores. The differences in comorbidities diminished, except for inflammatory cytokine levels, with a notable reduction in inflammatory cytokines observed in the glucocorticoid group, after matching 125 pairs based on propensity scores. Late treatment failure was more prevalent in the glucocorticoid group (39.2% vs 24.8%, P=0.015), but this was primarily caused by radiographic progression. The incidences of respiratory failure, mechanical ventilation, and septic shock were similar between the groups. Logistic regression analyses revealed that glucocorticoids reduced the risk of treatment failure ( OR=0.367, 95% CI 0.165-0.818, P=0.014). The 30-day in-hospital mortality rates were comparable (8.0% in glucocorticoids vs 7.2% in controls, P=0.811), with indications that glucocorticoids may exert a protective effect on mortality. The PSI score was determined as the sole independent risk factor for 30-day in-hospital mortality ( OR=1.077, 95% CI 1.032-1.123, P=0.001). No evidence indicated that glucocorticoids increased the incidence of hyperglycemia, gastrointestinal bleeding, or 30-day infection recurrence. Conclusion:Glucocorticoids reduce inflammatory cytokine levels and are potentially related to decreased treatment failure and mortality in patients with neutropenic pneumonia classified as PSI Ⅳ and Ⅴ among hematological patients.

Adipose stem cells (ADSCs) are adult stem cells that originate from the mesoderm and exist in the adipose tissue matrix. They have strong proliferative ability and multi-directional differentiation potential. Exosomes are membranous vesicles released into the extracellular matrix after the fusion of intracellular vesicles and cell membranes. They have the characteristics of small size and can pass through biological cell barriers, and can mediate information exchange between cells. At present, the technology of isolating exosomes from ADSCs is quite mature and has been widely applied in various medical fields. This article will review the research progress of adipose stem cell exosomes (ADSCsexo) in skin wounds and tissue repair.