ObjectiveTo investigate the therapeutic effect and mechanism of Xueshisanjia San against liver fibrosis by regulating PTEN-induced putative kinase （PINK1）/Parkin signaling pathway-mediated mitophagy. MethodsForty specific pathogen free （SPF）-grade male C57BL/6 mice were randomized into the control， model， silibinin （100 mg·kg^-1）， high-dose （15.16 g·kg^-1） Xueshisanjia San， and low-dose （7.58 g·kg^-1） Xueshisanjia San groups. The mouse model of liver fibrosis was constructed by intraperitoneal injection of 20% carbon tetrachloride solution. The treatment lasted for 6 weeks. Blood was collected from the abdominal aorta after intraperitoneal anesthesia， and the liver was separated. Liver pathology was examined by hematoxylin-eosin （HE） staining， Masson staining， and Sirius Red staining. Transmission electron microscopy （TEM） was employed to observe the mitochondrial morphology in the liver tissue. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， C-reactive protein （CRP）， total bilirubin （TBil）， transforming growth factor-β₁ （TGF-β₁）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） in the serum of mice were measured by enzyme-linked immunosorbent assay. Immunohistochemistry， immunofluorescence assay， and Western blot were employed to determine the protein levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and collagen Ⅰ， as well as mitophagy markers microtubule-associated protein 1 light chain 3 （LC3）， p62， Beclin-1， PINK1， Parkin， and translocase of outer mitochondrial membrane 20 （TOM20）. ResultsCompared with the control group， the model group exhibited elevated levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， pathological changes such destroyed structure of hepatic lobules， disarrangement of hepatic cells， and collagen accumulation， swollen， vacuolated， and fragment mitochondria， down-regulated expression of p62 and TOM20， and up-regulated expression of LC3， Beclin-1， PINK1， and Parkin （P<0.05）. Compared with the model group， all the treatment groups exhibited declined levels of ALT， AST， CRP， TBil， IL-6， TGF-β₁， and TNF-α in the serum （P<0.05）， alleviated pathological damage of liver tissue and mitochondrial damage， up-regulated expression of p62 and TOM20， and down-regulated expression of α-SMA， COL1A1， LC3， Beclin1， PINK1， and Parkin （P<0.05）. ConclusionXueshisanjia San may prevent excessive mitophagy and improve mitochondrial quality by inhibiting PINK1/Parkin signaling pathway， thereby alleviating liver fibrosis.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

Objective:To evaluate the efficacy and safety of low-dose post-transplant cyclophosphamide (PTCY) combined with anti-thymocyte globulin (ATG) in preventing graft-versus-host disease (GVHD) in children with β-thalassemia after hematopoietic stem-cell transplantation (HSCT).Method:A retrospective analysis was conducted on 42 children with transfusion-dependent β-thalassemia who underwent HSCT at Zhongshan Hospital, Xiamen University between March 2019 and June 2023. Based on donor source, recipients were grouped into the haploidentical donor group (Haplo-RD, 10 cases) and the unrelated donor group (UD, 32 cases). The UD group was further subdivided into HLA 8/10 matched (2 cases), HLA 9/10 matched (15 cases), and fully HLA-matched (15 cases). The conditioning regimen included fludarabine, busulfan, cyclophosphamide, and thiotepa. GVHD prophylaxis consisted of ATG (4.5 mg/kg), cyclophosphamide (25 mg/kg for 2 days), cyclosporine A (CsA), and mycophenolate mofetil (MMF). Engraftment, GVHD incidence, survival, mortality, and virus reactivation rates were evaluated.Result:The median age was 6 years (range, 2~12). All patients achieved hematopoietic reconstitution. The median times to neutrophil and platelet engraftment were 11 days (range, 10~15) days and 12 days (range, 6~31), respectively. All recipients had >95% peripheral blood STR chimerism by day 30. Grade Ⅲ~Ⅳ acute GVHD occurred in 3 recipients (7.14%), and chronic GVHD occurred in 5 recipients (11.90%) -1 case extensive, 4 cases limited. Both overall survival (OS) and disease-free survival (DFS) were 92.86%. All children in the Haplo-RD group achieved DFS. Eight patients developed cytomegalovirus (CMV) viremia (no CMV disease), with a reactivation rate of 19.05%, and 9 recipients had BK virus-related urinary tract infections (6 cases in the UD group and 3 cases in the Haplo-RD group), for a total incidence of 21.43%.Conclusion:The combination of low-dose PTCY and ATG is a safe and effective strategy to prevent GVHD following haploidentical or unrelated donor HSCT in pediatric β-thalassemia. It is associated with reduced infection and viral reactivation post-transplant and contributes to high survival rates.

Objective:To investigate the efficacy and safety of the combination therapy of venetoclax (VEN) and azacitidine (AZA) in treatment of newly diagnosed elderly patients with acute myeloid leukemia (AML).Methods:A retrospective cohort study was conducted. The clinical data of 17 newly diagnosed elderly AML patients who received VEN+AZA regimen at the First Hospital of Putian City from April 2021 to June 2023 were collected. Treatment outcomes and adverse events were analyzed. Survival curves were plotted by using the Kaplan-Meier method, and intergroup comparisons were performed by using the log-rank test.Results:Among the 17 patients, the median age [ M ( Q1, Q3)] was 70 (68, 74) years, with 11 males (64.7%) and 6 females (35.3%). The median number of treatment courses was 4.0 (2.5, 8.5). After the first course, the composite complete remission (cCR) rate was 41.2% (7/17), minimal residual disease (MRD) negativity rate was 5.9% (1/17), and overall response rate (ORR) was 82.4% (14/17). By the end of follow-up in September 2023, the cCR rate reached 64.7% (11/17), MRD negativity rate was 52.9% (9/17), and ORR was 88.2% (15/17). The median number of courses to achieve cCR was 1.0 (1.0, 2.0), and to achieve MRD negativity was 3.0 (2.0, 3.5). The follow-up rate was 88.2% (15/17), and the median follow-up time was 17.3 months (95% CI: 7.0-27.6 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 1.7-11.3 months), and median overall survival (OS) time was 12.0 months (95% CI: 0.3-23.7 months). The median OS time after progression was 1.5 months (95% CI: 1.0-2.0 months). All patients experienced hematological adverse events, with 94.1% (16/17) experiencing grade ≥ 3 hematological adverse events. The most common non-hematological adverse event was infection (88.2%, 15/17), with the lung being the most frequent site of infection (82.4%, 14/17), while 41.2% (7/17) of patients had pre-existing infections before treatment. Conclusions:The VEN+AZA regimen demonstrates high remission rates and significant efficacies in treating newly diagnosed elderly AML patients. Although adverse events occur in nearly all patients, most are able to tolerate the treatment.

Objective To develop the Children's Screen Interaction Quality Questionnaire(CSIQ)suit-able for measuring Chinese children aged 0 to 4 years,and to test its reliability and validity.Methods The purposive sampling method was used,and the guardians of 30 normal children aged 0 to 4 years undergoing physical examinations in the Department of Child Health Care of Guiyang Maternal and Child Health Care Hospital from February to April 2023 were selected as the interview objects.25 initial items were constructed through literature review,semi-structured interviews,and the Delphi expert consultation method.With the convenience sampling method,2 242 guardians of children aged 0 to 4 years old in the small and middle classes of 9 kindergartens in Guiyang City,Zunyi City,and Renhuai City were surveyed for item analysis,exploratory factor analysis,confirmatory factor analysis,and reliability and validity analysis.Results Exploratory factor a-nalysis extracted three factors,namely screen content interaction,reality interaction,and media interaction,with a total of 12 items.The cumulative variance explained rate of the 3-factor model was 69.829％.Confirma-tory factor analysis supported the three-factor model of CSIQ:x2/df=4.424,root mean square error of ap-proximation(RMSEA)=0.066,normed fit index(NFI)=0.955,comparative fit index(CFI)=0.965,incre-mental fit index(IFI)=0.965,Tucker-Lewis index(TLI)=0.955,goodness-of-fit index(GFI)=0.955,and the CSIQ had good convergent validity and discriminant validity.Conclusion The CSIQ has good reliability and validity.

Objective:To explore the diagnostic value of transcranial magnetic stimulation (TMS), transsacral magnetic root stimulation combined with sacral reflexes, external anal sphincter electromyography and pudendal nerve somatosensory evoked potentials in the assessment of neurogenic lower urinary tract dysfunction (NLUTD).Methods:Twenty-one NLUTD patients (1 with a supra-pontine lesion, 5 with a spinal cord injury, 5 with a cauda equina injury, and 10 with pelvic floor disorders) were enrolled. Needle electromyography (EMG) was used to record TMS-induced and transsacral magnetic stimulation-induced motor evoked potentials (tc-MEPs and ts-MEPs, respectively) related to the external anal sphincter (EAS). The dorsal nerve of the penis or clitoris was stimulated electrically to record the latency of the sacral reflex related to the EAS. Central motor conduction time (CMCT) and the tc/ts-MEP latency ratio were calculated to distinguish central from peripheral lesions.Results:In the one patient with a supra-pontine lesion, although the tc-MEP and ts-MEP latencies were within normal limits, the CMCT was prolonged (28.2ms) and the tc/ts-MEP ratio was large (7.4). Among the five patients with a spinal cord injury, one exhibited prolonged tc-MEP latency (50.6ms) and CMCT (47.8ms), along with a large tc/ts-MEP ratio (18.1). In the five patients with cauda equina injury and the ten with NLUTD secondary to pelvic floor disorders, CMCT was within the normal range [averaging (22.9±4.9ms) and (24.2±3.5ms), respectively], but the ts-MEP latency was prolonged [(7.1±2.1ms) and (8.6±3.7ms), respectively], and the tc/ts-MEP ratio was small [(4.4±0.9) and (4.3±1.5), respectively]. The tc/ts-MEP ratio demonstrated the best rate of abnormality detection (93.8%), with an area under the curve of 0.99, indicating good sensitivity.Conclusions:The tc/ts-MEP ratio can be useful for distinguishing central and peripheral lesions. A markedly increased tc/ts-MEP ratio may suggest central nervous system injury, whereas a decreased ratio may indicate peripheral nervous system injury.

Objective:To investigate the application value of dermoscopy and reflectance confocal microscopy (RCM) in identifying field cancerization in actinic keratosis (AK) in the elderly.Methods:A retrospective analysis was conducted on clinical, dermoscopic, and RCM features of elderly (> 60 years old) patients, who were confirmedly diagnosed with AK and had complete medical records at Shanghai Skin Disease Hospital from January 2022 to December 2023.Results:A total of 132 elderly patients with AK were included. Dermoscopy showed brownish-gray pseudonetwork pigment patterns, follicular horn plugs, irregular branched vessels, and rosette signs in AK lesions. Histopathological examination in 51 patients revealed that 47 (92.16%) were confirmedly diagnosed with AK. Field cancerization was observed in 106 patients (80.3%), among whom 66 (62.26%) had irregular branched vessels, 88 (83.02%) predominantly exhibited brownish-gray pseudonetwork pigment patterns, and 83 (78.30%) showed scattered brown pigment networks/fingerprint-like patterns. Post-treatment follow-up of 63 patients showed varying degrees of changes in vascular and pigment structures by dermoscopy, with significant reductions in follicular horn plugs and superficial yellow-white scales or keratin masses. RCM examinations in 41 AK patients all showed disordered arrangements of keratinocytes presenting as atypical honeycomb patterns, with atypical cells in the AK lesions; in the field cancerization areas of 20 patients, RCM revealed keratinocytes disorderedly arranged in an irregular honeycomb pattern, with some keratinocytes exhibiting mild atypia. Thirty-four AK patients underwent dynamic RCM monitoring before and after 1, 3 and 6 months of ALA-PDT treatment, which showed gradual regularization of arrangements of keratinocytes and reduction of atypical cells, as well as reappearance of atypical keratinocytes upon recurrence.Conclusions:The incidence of field cancerization was relatively high in elderly AK patients. Dermoscopy and RCM are helpful for the early identification of AK and field cancerization, especially in patients with multiple lesions and with difficulties in multi-site biopsy.

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry