Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Objective:To explore common characteristics and core challenges in the family parenting process of preschool children, identify key issues in parenting practices in rural revitalization areas, and provide a reference for developing localized family intervention strategies in China.Methods:Using purposive sampling, caregivers of preschool children ( n=26) were recruited from a kindergarten in Shuangbai County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, from May to August 2024. A descriptive qualitative research method was adopted. Directed content analysis and conventional content analysis were combined to analyze interview transcripts and family parenting records, extracting core themes and characteristic issues in parenting practices. Results:A total of 881 minutes of interviews were conducted, resulting in approximately 260 000 words of transcripts and text materials. A total of five core themes and 13 sub-themes were summarized, covering access to health information and scientific parenting knowledge, imbalance between parenting needs and objective resource supply, safety care, responsive care, and weak family collaboration systems.Conclusions:Families in rural revitalization areas currently face problems such as limited access to information, insufficient scientific parenting resources, and weak family collaboration functions. It is recommended to optimize parenting practices by deepening the integration of medical and educational resources, strengthening health information channels, and building an integrated "family-school-community" intervention framework.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Objective To investigate the mechanism of autophagy induced by House dust mites(HDM)on airway epithelial tight junction through β-catenin-Snail signaling pathway.Methods Human bronchial epithelial cells(16HBE)were stimulated with HDM at different time points(0,3,6,12,24,48 h)and different concen-trations(0,40,100,200 μg/mL)to screen the appropriate stimulation concentration and stimulation time.16HBE cells were treated with oxidative stress inhibitor N-acetylcysteine(NAC),autophagy inhibitor 3-methylad-enine(3-MA),HDM,and their combinations.Cells were transfected with mCherry-EGFP-LC3B,Beclin-1-siRNA,and ATG14-siRNA lentivirus and then stimulated with NAC and HDM.Immunofluorescence was used to detect the expression levels of autophagy-related protein LC3B,tight junction-related proteins Occludin,and ZO-1 in airway epithelial cells.The level of reactive oxygen species(ROS)was detected by using DCFH-DA in each group.The protein expression levels of Occludin,ZO-1,LC3B,Beclin-1,ATG5,ATG14,P62,Snail,β-catenin and p-β-catenin were detected by Western blot method.Results Immunofluorescence results showed that compared with the control group,200 μg/mL HDM stimulation induced cellular autophagy,increased the expression level of LC3B protein,and promoted the level of ROS,all with statistical significances(all P<0.05).Compared with the HDM group,the HDM+3-MA,HDM+ATG14-si,and HDM+Beclin-1-si groupsall showed significantincreases in the expression levels of tight junction-related proteins Occludin and ZO-1(P<0.05).The HDM+NAC group demonstrated significant decreases both in the level of ROS andin the expression level of LC3B protein.Western blot results revealed that compared with HDM,3-MA and autophagy protein low-expression beads(Beclin-1-si,ATG14-si)attenuated HDM-induced cellular autophagy(P<0.05),inhibited HDM-induced upregulation of Snail and p-β-catenin expression,and improved HDM-induced decreases in Occludin and ZO-1(P<0.05).Moreover,compared with the HDM group,the NAC+HDM group exhibited significant decreases both in the conversion of LC3BⅠ to LC3BⅡ(P<0.001)in the protein levels of Snail,p-β-catenin,Beclin-1 and ATG14(P<0.01),but significant increases in the protein levels of Occludin and ZO-1(P<0.05).Conclusion HDM affects the tight connections between airway epithelial cells by inducing autophagy,which may be attributed to the β-catenin-Snail signaling pathway.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Objective To investigate the potential mechanism of miR-21-5p in alleviating cerebral ischemia-reperfusion injury by targeting STAT3.Methods The HT22 cells were induced by OGD/R to construct a cell model of cerebral ischemia reperfusion injury.The expression of miR-21-5p was detected by RT-qPCR.The CCK-8 assay,TUNEL staining and flow cytometry were respectively used to detect the cell viability and apoptosis.ELISA assay was used to determine the contents of inflammatory factors IL-6,IL-10 and TNF-α in the cell supernatant.Western blot was used to detect the expression levels of p-STAT3/STAT3,Cleaved-Caspase-3,Bax and Bcl-2 proteins.The TargetScan database was used to predict the binding sites of miR-21-5p and STAT3.The dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-21-5p and STAT3.Results The relative expression level of miR-21-5p was down-regulated in HT22 cells which induced by OGD/R(P<0.001).The cell viability(P<0.0001)was decreased and the apoptosis rate(P<0.001)was increased in OGD/R induced-HT22 cells.The contents of pro-inflammatory factors IL-6(P<0.001)and TNF-α(P<0.001)was increased,while the content of anti-inflammatory factor IL-10(P<0.001)decreased.After transfection with miR-21-5p mimic,cell viability was enhanced,apoptosis rate was reduced and neuroinflammation was inhibited.MiR-21-5p could target and bind to STAT3.After miR-21-5p inhibitor transfection,cell viability decreased,apoptosis was promoted,and neuroinflammation occurred;STAT3 inhibitor Stattic could reverse the effect of miR-21-5p inhibitor.Conclusion MiR-21-5p could specifically bind to STAT3 and reduce the neuroinflammation and apoptosis of OGD/R induced-HT22 cells.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.