Breast cancer has become the malignant tumor with the highest incidence rate among women， seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia， and from pre-cancerous lesions to cancerous lesions， is a long-term progressive process. Therefore， early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer， which is mainly based on surgery and systemic treatment， whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer， surgery is also the mainstay of treatment. In recent years， traditional Chinese medicine （TCM） has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions， TCM compound prescriptions， single herbs or herb pairs， and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion， promote the apoptosis and autophagy of tumor cells， and regulate the cell cycle and the immune microenvironment， thus exerting anti-tumor effects. At the same time， they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However， the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Wnt/β-catenin， and Notch， which still need to be verified by a large number of clinical and experimental studies. Therefore， this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years， aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

This study investigated the protective effect of arbutin(Arb) in yam on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in a mouse model and revealed its possible mechanism of action by metabolomics technology, providing a theoretical basis for clinical treatment of ALI. SPF BALB/c mice were randomly divided into normal control group, model group, resveratrol(Rv)-positive control group, Arb low-dose(15 mg·kg~(-1)) group, and Arb high-dose(30 mg·kg~(-1)) group. The LPS-induced ALI model was established in all groups except the normal control group. Hematoxylin-eosin(HE) staining, TUNEL staining, and WBP whole-body non-invasive pulmonary function testing were used to evaluate the degree of lung tissue damage and lung function changes. Enzyme-linked immunosorbent assay(ELISA) was used to detect the level of inflammatory factors in lung tissue. Flow cytometry was used to analyze the M1/M2 polarization status of macrophages in lung tissue. Western blot was used to detect the expression levels of the TLR4 signaling pathway and related apoptotic proteins. Liquid chromatograph-mass spectrometer(LC-MS) metabolomics was used to analyze the changes in serum metabolic profile after Arb intervention. The results showed that Arb pretreatment significantly alleviated LPS-induced lung tissue injury, improved lung function, reduced the levels of pro-inflammatory factors(IL-6, TNF-α, IL-18, and IL-1β), and regulated the polarization status of M1/M2 macrophages. In addition, Arb inhibited the activation of the TLR4 signaling pathway, reduced the expression of pro-apoptotic proteins such as Bax, caspase-3, and caspase-9, up-regulated the level of Bcl-2 protein, and inhibited apoptosis of lung cells. Metabolomic analysis showed that Arb significantly improved LPS-induced metabolic abnormalities, mainly involving key pathways such as galactose metabolism, phenylalanine metabolism, and lipid metabolism. In summary, Arb can significantly reduce LPS-induced ALI by regulating the release of inflammatory factors, inhibiting the activation of the TLR4 signaling pathway, improving metabolic disorders, and regulating macrophage polarization, indicating that Arb has potential clinical application value.
Animals ; Acute Lung Injury/chemically induced* ; Mice ; Mice, Inbred BALB C ; Arbutin/administration & dosage* ; Male ; Toll-Like Receptor 4/immunology* ; Apoptosis/drug effects* ; Lung/metabolism* ; Signal Transduction/drug effects* ; Protective Agents/administration & dosage* ; Humans ; Macrophages/immunology* ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: To evaluate the effectiveness of the innervated medial plantar flap for reconstructing soft tissue defects, particularly in the weight-bearing zone, after resection of foot tumors. METHODS: A retrospective analysis was conducted on 12 patients with malignant skin and soft tissue tumors of the foot treated between October 2023 and December 2024. The cohort included 8 males and 4 females, aged 42-67 years (mean, 57.5 years). Tumor types comprised malignant melanoma (5 cases), squamous cell carcinoma (4 cases), arsenical keratosis (2 cases), and tumor-induced osteomalacia (1 case). Soft tissue defects located in the heel weight-bearing region in 10 cases and non-weight-bearing ankle region in 2 cases, with defect sizes ranging from 4.0 cm×3.0 cm to 6.0 cm×4.0 cm. Preoperative photon-counting CT angiography (PC-CTA) was performed to assess the medial plantar artery and its perforators. All patients underwent radical tumor resection with confirmed negative margins. The resulting defects were reconstructed using a innervated medial plantar flap incorporating sensory branches of the medial plantar nerve. The flap donor site was covered with a split-thickness skin graft harvested from the ipsilateral inguinal region. RESULTS: The operation was successfully completed in all 12 patients. All flaps survived completely without vascular compromise, partial necrosis, or total loss. Incisions healed primarily without dehiscence or infection. Minor skin graft necrosis occurred at the donor site in 3 patients, which healed within 2-3 weeks with routine dressing changes. No donor site complication (e.g., tendon or nerve injury) occurred. Patients were followed up 2-16 months (mean, 10.3 months). At last follow-up, there was no tumor recurrence. Flaps exhibited good color and texture match with surrounding tissue, restored sensation, and all feet achieved normal weight-bearing activity. CONCLUSION The innervated medial plantar flap, precisely designed based on PC-CTA localization, provides reliable blood supply and effective sensory restoration. It is an ideal method for reconstructing soft tissue defects after foot tumor resection, especially in the heel weight-bearing region.
Humans ; Male ; Middle Aged ; Female ; Plastic Surgery Procedures/methods* ; Adult ; Aged ; Retrospective Studies ; Soft Tissue Neoplasms/surgery* ; Surgical Flaps/blood supply* ; Foot/surgery* ; Skin Neoplasms/surgery* ; Soft Tissue Injuries/surgery* ; Carcinoma, Squamous Cell/surgery* ; Treatment Outcome ; Skin Transplantation/methods* ; Melanoma/surgery*

Objective To explore the application of Mini-CEX oriented by nurses'core competencies in the clinical teaching of intern nursing students.Methods A total of 50 students,interning in the First Affiliated Hospital of Kunming Medical University from January 1,2023 to April 30,2024,were randomly divided into experimental group and control group,with 25 students in each group.The control group was taught by traditional clinical teaching methods,and the experimental group by Mini-CEX.The data indicators of the two groups of intern nursing students were analyzed and compared at entry into and exit from the department,respectively.Results The scores of the two groups were higher than those at entry into the department(P<0.05),and the intern nursing students in the experimental group had excellent scores in nursing consultation,nursing examination,nursing diagnosis,nursing measures,humanistic care,organizational effectiveness,health consultation,and overall evaluation,and the scores were higher than those of the control group(P<0.05).The improvement in all the scores was also better than that of the control group(P<0.05).Conclusion Mini-CEX,which is oriented to the nurse'core competencies of nurses,can improve the clinical nursing abilities of intern nursing students and enhance the cultivation effect of clinical practice skills.