Breast cancer (BC) is one of the most prevalent malignant tumors affecting women worldwide, with its incidence rate continuously increasing. As a result, treatment strategies for this disease have received considerable attention. Research has highlighted the crucial role of the Hedgehog (Hh) signaling pathway in the initiation and progression of BC, particularly in promoting tumor growth and metastasis. Therefore, molecular targets within this pathway represent promising opportunities for the development of novel BC therapies. This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC. By conducting a comprehensive review of various natural compounds, including polyphenols, terpenes, and alkaloids, we reveal both common and unique regulatory mechanisms that influence this pathway. This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC. Furthermore, by exploring the structure-activity relationships between these compounds and their molecular targets, we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway. These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics. Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

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

Objective:To analyze the equity of elderly care institution resource allocation in Northeast China and its influencing factors,and provide certain reference for the further development of elderly care care in Northeast China.Methods:The total amount of nursing institution resource allocation and the per capita old and above per 1 000 km2 were summarized by using general descriptive analysis.The Lorenz curve,Gini coefficient,and Theil index were calculated to evaluate the equity of nursing institution resource allocation.Results:Jilin Province did not have an advantage in the total allocation of elderly care insitution resources in Northeast China.In terms of resource allocation per 1 000 km2,Heilongjiang Province still has considerable room for improvement.The overall arc of the Lorenz curve for allocating resources by geographical area has become smaller year by year,while the overall arc of the Lorenz curve for allocating resources by population has become larger year by year.Conclusion:The equity of allocating institution home resources by population has generally weakened over the years,while the equity of allocating elderly care institution resources by geographical area has generally strengthened over the years.The development pressure of nursing care in Liaoning Province is relatively large,and efforts should be made to enhance the fairness of nursing home resource allocation.

Objective:To explore the impact of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/tumor protein 53 (TP53) expression on the 68Ga-prostate specific membrane antigen (PSMA)-11 and 18F-FDG molecular imaging phenotypes in primary prostate cancer. Methods:A retrospective study was conducted on 75 prostate cancer patients (age (67.9±6.3) years) who received both 68Ga-PSMA-11 and 18F-FDG PET/CT imaging on initial diagnosis and subsequent radical prostatectomy at Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, between Auguest 2018 and July 2022. The correlation between PTEN and TP53 expression in prostate cancer and molecular imaging phenotype was analyzed by χ2 test, Kruskal-Wallis rank sum test and Bonferroni method based on the uptake of imaging agents in primary lesions and the results of immunohistochemical analysis of surgical specimens. Results:In prostate cancer tissues with PTEN expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 14/14 and 11/14, with the SUV max of 7.70(6.15, 11.05) and 15.55(6.75, 23.49) respectively. In prostate cancer tissues with TP53 expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 10/10 and 6/10, with the SUV max of 7.70(6.95, 8.05) and 9.50(5.38, 19.89) respectively. In prostate cancer tissues with different expression patterns of PTEN and TP53, there were significant differences in the positive rates of 18F-FDG uptake ( χ2=20.45, P< 0.001), 68Ga-PSMA-11 uptake ( χ2=14.97, P=0.002), and the SUV max of 68Ga-PSMA-11 uptake ( H=9.62, P=0.022). Additionally, patients with concurrent loss of PTEN and TP53 expression in the primary tumor had significantly lower SUV max of 68Ga-PSMA-11 uptake compared to those with expression of both PTEN and TP53 (5.70(4.40, 11.70) vs 20.95(13.73, 37.58); P=0.003 (Bonferroni method corrected)). Conclusion:PTEN/TP53 expression is associated with the 68Ga-PSMA-11 and 18F-FDG molecular imaging phenotype in primary prostate cancer.

Objective:To explore the impact of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/tumor protein 53 (TP53) expression on the 68Ga-prostate specific membrane antigen (PSMA)-11 and 18F-FDG molecular imaging phenotypes in primary prostate cancer. Methods:A retrospective study was conducted on 75 prostate cancer patients (age (67.9±6.3) years) who received both 68Ga-PSMA-11 and 18F-FDG PET/CT imaging on initial diagnosis and subsequent radical prostatectomy at Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, between Auguest 2018 and July 2022. The correlation between PTEN and TP53 expression in prostate cancer and molecular imaging phenotype was analyzed by χ2 test, Kruskal-Wallis rank sum test and Bonferroni method based on the uptake of imaging agents in primary lesions and the results of immunohistochemical analysis of surgical specimens. Results:In prostate cancer tissues with PTEN expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 14/14 and 11/14, with the SUV max of 7.70(6.15, 11.05) and 15.55(6.75, 23.49) respectively. In prostate cancer tissues with TP53 expression loss, the positive rates of 18F-FDG uptake and 68Ga-PSMA uptake were 10/10 and 6/10, with the SUV max of 7.70(6.95, 8.05) and 9.50(5.38, 19.89) respectively. In prostate cancer tissues with different expression patterns of PTEN and TP53, there were significant differences in the positive rates of 18F-FDG uptake ( χ2=20.45, P< 0.001), 68Ga-PSMA-11 uptake ( χ2=14.97, P=0.002), and the SUV max of 68Ga-PSMA-11 uptake ( H=9.62, P=0.022). Additionally, patients with concurrent loss of PTEN and TP53 expression in the primary tumor had significantly lower SUV max of 68Ga-PSMA-11 uptake compared to those with expression of both PTEN and TP53 (5.70(4.40, 11.70) vs 20.95(13.73, 37.58); P=0.003 (Bonferroni method corrected)). Conclusion:PTEN/TP53 expression is associated with the 68Ga-PSMA-11 and 18F-FDG molecular imaging phenotype in primary prostate cancer.

Objective:To analyze the equity of elderly care institution resource allocation in Northeast China and its influencing factors,and provide certain reference for the further development of elderly care care in Northeast China.Methods:The total amount of nursing institution resource allocation and the per capita old and above per 1 000 km2 were summarized by using general descriptive analysis.The Lorenz curve,Gini coefficient,and Theil index were calculated to evaluate the equity of nursing institution resource allocation.Results:Jilin Province did not have an advantage in the total allocation of elderly care insitution resources in Northeast China.In terms of resource allocation per 1 000 km2,Heilongjiang Province still has considerable room for improvement.The overall arc of the Lorenz curve for allocating resources by geographical area has become smaller year by year,while the overall arc of the Lorenz curve for allocating resources by population has become larger year by year.Conclusion:The equity of allocating institution home resources by population has generally weakened over the years,while the equity of allocating elderly care institution resources by geographical area has generally strengthened over the years.The development pressure of nursing care in Liaoning Province is relatively large,and efforts should be made to enhance the fairness of nursing home resource allocation.

Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.There-fore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural com-pounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehen-sive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

Objective:To evaluate the detection rate and distribution characteristics of lesions in patients with biochemical recurrence (BCR) after radical prostatectomy for prostate cancer by 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT. Methods:From January 2020 to March 2024, 68Ga-PSMA-11 PET/CT examination results of 172 patients (age (69.4±6.5) years) with BCR after radical prostatectomy in Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The relationship between prostate specific antigen (PSA) levels and 68Ga-PSMA-11 PET/CT detection rate was explored. The location and quantity of lesions detected by 68Ga-PSMA-11 PET/CT were analyzed in BCR patients with clear location after local treatment, and data were analyzed by Fisher exact test. Results:The detection rate of 68Ga-PSMA-11 PET/CT in patients with BCR was 70.35%(121/172). The positive detection rate increased with the increase of PSA level, with detection rates of 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1.0 μg/L, 1.0 μg/L≤PSA<1.5 μg/L and PSA≥1.5 μg/L groups of 49.12%(28/57), 67.24%(39/58), 15/16 and 95.12%(39/41), respectively. After local treatment, 64 cases were diagnosed with 95 recurrent and metastatic lesions. Among them, 22(34.38%) had simple prostate bed recurrence, 23(35.94%) had simple lymph node metastasis, 7(10.94%) had simple bone metastasis, and 12(18.75%) had multi regional metastasis. The proportion of bone metastasis (18.75%, 12/64) was significantly lower than that of prostate bed recurrence and lymph node metastasis (both 50.00%(32/64); both P=0.002). Conclusions:68Ga-PSMA-11 PET/CT has a high detection rate in patients with BCR after radical prostatectomy, especially in patients with high PSA levels. The lesions are mainly distributed in the prostate bed and lymph nodes, while bone metastases are relatively rare, which provide a theoretical basis for the selection of more accurate treatment plans for BCR patients in the future.

OBJECTIVE: To evaluate the regulatory effect of berberine on autophagy and apoptosis balance of fibroblast-like synoviocytes (FLSs) from patients with in rheumatoid arthritis (RA) and explore the mechanism. METHODS: The inhibitory effect of 10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine on RA-FLS proliferation was assessed using CCK-8 method. Annexin V/PI and JC-1 immunofluorescence staining was used to analyze the effect of berberine (30 μmol/L) on apoptosis of 25 ng/mL TNF-α- induced RA-FLSs, and Western blotting was performed to detect the changes in the expression levels of autophagy- and apoptosis-related proteins. The cells were further treated with the autophagy inducer RAPA and the autophagy inhibitor chloroquine to observe the changes in autophagic flow by laser confocal detection of mCherry-EGFP-LC3B. RA-FLSs were treated with the reactive oxygen species (ROS) mimic H₂O₂ or the ROS inhibitor NAC, and the effects of berberine on ROS, mTOR and p-mTOR levels were observed. RESULTS: The results of CCK-8 assay showed that berberine significantly inhibited the proliferation of RA-FLSs in a time- and concentration-dependent manner. Flow cytometry and JC-1 staining showed that berberine (30 μmol/L) significantly increased apoptosis rate (P < 0.01) and reduced the mitochondrial membrane potential of RA-FLSs (P < 0.05). Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01) and increased the expression of p62 protein in the cells (P < 0.05). Detection of mCherry-EGFP-LC3B autophagy flow revealed obvious autophagy flow block in berberine-treated RA-FLSs. Berberine significantly reduced the level of ROS in TNF-α-induced RA-FLSs and upregulated the expression level of autophagy-related protein p-mTOR (P < 0.01); this effect was regulated by ROS level, and the combined use of RAPA significantly reduced the pro-apoptotic effect of berberine in RA-FLSs (P < 0.01). CONCLUSION Berberine can inhibit autophagy and promote apoptosis of RA-FLSs by regulating the ROS-mTOR pathway.
Humans ; Synoviocytes ; Berberine/metabolism* ; Reactive Oxygen Species/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Hydrogen Peroxide/metabolism* ; Sincalide/metabolism* ; Cell Proliferation ; Arthritis, Rheumatoid/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis ; Fibroblasts ; Autophagy ; Cells, Cultured