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Background and purpose: Effective treatment for cervical cancer patients is one of the global strategies to eliminate cervical cancer. By analyzing the metastasis characteristics and survival status of patients with distant metastasis of cervical cancer from a hospital-based cancer registry data, our study provided real-world evidence for better survival of cervical cancer and finally eliminating cervical cancer. Methods: A total of 572 cervical cancer patients who had metastasis cancer at the initial diagnosis or developed distant metastasis during follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The first follow-up date was the diagnose date of metastasis, and the last follow-up date was November 1, 2020. Kaplan-Meier method was applied in evaluating the 1-, 3- and 5-year overall survival (OS) rates for overall and site-specific patients. Results: The median follow-up time was 38.93 months, and 348 cases died during the follow-up. 72.55% were single site metastasis, and 27.45% were multiple metastases. Among all metastatic sites, the proportion of lung metastasis was the highest, 41.26%, 15.21% to bone, and 11.54% to liver. After metastasis, the 1-year, 3-year and 5-year OS rates were 62.29% (95% CI: 62.25-62.33), 33.13% (95% CI: 33.08-33.18) and 23.42% (95% CI: 23.37-23.47), respectively. In single site metastasis, 1-year OS was the highest after metastasis to the lung (72.52%). Besides, there was no significant difference among different metastatic sites, both in 3-year and 5-year OS. Conclusion: The most frequent distant metastatic sites of cervical cancer are lung, bone and liver. The survival rate after metastasis is poor. Further research with systematic treatment strategy is required for better survival.

Background and purpose: Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration, and the 1-, 3- and 5-years observed overall survival (OS) rates and disease-free survival (DFS) rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China. Methods: A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study. Clinical information and the follow-up endpoint data were collected through medical records review, telephone visits and death registry data linkage. The last follow-up date was November 30, 2023. Kaplan-Meier method was applied in evaluating the 1-, 3- and 5-year OS rate and DFS rate, and survival data were described by different subgroups including age group, gender, treatment period, tumor staging, and pathological characteristics. Results: With a median follow-up time of 50.99 months, the 5-year OS rate of surgically resected gastric cancer patients was 70.37%, and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%. The 5-year OS rates of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 94.32%, 82.56%, 51.01% and 23.97%, respectively. The differences in survival among patients with different age, tumor location, gross classification, Borrmann classification and Laurence classification were significant. Conclusion: Staging is an important factor directly affecting the survival of gastric cancer patients. Screening and early diagnosis and treatment in large population, especially high-risk group, should be strengthened to further improve the patients’ survival.

Background and purpose: Artificial intelligence (AI) technology is increasingly being used in the medical field. This study aimed to assess the effectiveness of artificial intelligence ultrasound system for identifying breast lesions in Chinese women and its role in breast cancer early detection. Methods: A prospective study was conducted on healthy women aged 35-74 years who came to Fudan University Shanghai Cancer Center from August 2020 to December 2020 for breast ultrasonography. All the women were examined by AI-assisted ultrasound first, and then by conventional ultrasonography. We compared the differences between AI-assisted ultrasound and conventional ultrasonography in identifying breast lesions in Chinese women. One year later, we looked up the hospital medical history and Shanghai Cancer Registration Management System for the final diagnosis of breast cancer. Results: A total of 360 women were included in the study and received breast examinations using both AI-assisted ultrasound and conventional ultrasound. A total of 2 504 breast lesions were detected, of which, 2 217 were detected by AI-assisted ultrasound, with a lesion recognition rate of 88.5%. Conventional ultrasound identified 1 090 lesions, with a lesion recognition rate of 43.5%. Using conventional ultrasound as the standard, the sensitivity and specificity of AI-assisted ultrasound for Breast Imaging Reporting and Data System (BI-RADS) level 4 and above lesions were 93.3% (95% CI: 80.7-98.3) and 100.0% (95% CI: 99.5-100.0), respectively. During one-year follow-up, 10 patients were diagnosed with breast cancer, and 8 of whom were identified by both AI-assisted ultrasound and conventional B ultrasound. The sensitivity of AI-assisted ultrasound and conventional ultrasound for breast cancer was 80.0% (95% CI: 44.2-96.4), and the specificity was 88.6% (95% CI: 84.6-91.6). Conclusion: AI-assisted ultrasound has good identification ability for breast lesions in Chinese women. The recognition ability for high-risk breast lesions (BI-RADS 4A and above) and early breast cancer is equivalent to that of conventional ultrasound, which is suitable for breast cancer screening in large-scale community of women with general risk.

Background and purpose: Currently, several studies have demonstrated that body mass index (BMI) is a prognostic factor in breast cancer. The study aimed to assess the association pattern of BMI with mortality risk among patients of different age groups. Methods: This retrospective cohort study included the clinical characteristics and survival status of 25 629 patients diagnosed with breast cancer and subsequently hospitalized in Fudan University Shanghai Cancer Center between January 1, 2008 and December 31, 2016. The association between BMI and prognosis of breast cancer patients in different age subgroups was analyzed using Cox proportional hazards regression model with restricted cubic splines adjusting the main prognostic factors. Results: BMI and age were both influencing factors of breast cancer prognosis, and there was a significant interaction (P = 0.011). The pattern of association between risk of death and BMI differed among different age groups. A "J-shaped" association between risk of death and BMI was observed in the patients younger than 35 years, with a BMI of 20.16 kg/m2 corresponding to the lowest risk of death. In the age group of 35-60 years, no significant change in the risk of death was observed in patients with BMI below 23 kg/m2, and the risk of death in patients with BMI above 23 kg/m2 increased with increasing BMI; A "U-shaped" association between risk of death and BMI was observed in the patients older than 60 years, with a BMI of 23.86 kg/m2 being the lowest. The risk of death was more sensitive to changes in BMI in patients aged less than 35 years than in those aged 35-60 years and those aged more than 60 years. Conclusion: BMI and age have a significant interaction in the prognosis of breast cancer when adjusted for potential confounding factors. The association pattern between the risk of death and BMI of patients in different age groups is different. For patients under 35 years old, the lowest risk of death corresponds to BMI at diagnosis of about 20 kg/m2, while for patients over 60 years old, the lowest risk of death corresponds to a BMI at diagnosis of about 24 kg/m2.

Background and purpose: Endocrine therapy has been one of the routine means of adjuvant therapy for patients with hormone receptor positive after surgery. This study aimed to analyze the factors influencing short-term effect (estrogen suppression effect) and long-term survival (disease-free survival, DFS) in patients with operable breast cancer after ovarian function suppression (OFS) therapy. Methods: DFS data and clinicopathological parameters for 435 patients with estrogen receptor (ER) positive breast cancer who underwent surgery and completed postoperative standard chemotherapy and endocrine therapy (OFS combined with tamoxifen or aromatase inhibitors) between June 2017 to June 2019 were obtained in Fudan University Shanghai Cancer Center. The authors performed univariate logistic regression and multivariate logistic regression to analyze the influencing factors of estrogen suppression, while log-rank test and COX proportional hazards regression model were used to analyze the influencing factors of disease-free survival. Results: The failure rate of estrogen suppression in patients aged ≤35 years was 8.7%, which was significantly higher than that in patients aged 35-40 years (1%, P0.05). Endocrine therapy regimen (HR = 0.49, P

To report the results of a single-arm, prospective partial breast irradiation (PBI) trial from China mainland using a dose of 40.05 Gy in 15 fractions delivered with intensity-modulated radiation therapy (IMRT) technique for patients with early stage breast cancer. Patients aged ≥ 50 years who underwent breast-conserving surgery for unifocal non-lobular invasive breast cancer, with pathological T1 disease, clear margins, negative axillary nodes, and positive hormonal receptors, were recruited. The primary endpoint was 3-year cosmetic deterioration, and secondary endpoints included adverse events, ipsilateral breast tumor recurrence (IBTR), regional recurrence, and survivals. This trial is registered with ClinicalTrials.gov (registration No. NCT03411174). From Jan of 2015 to July of 2018, 208 out of 222 patients recruited were evaluable and included in final analysis. The median follow-up was 66.3 (range: 42.0-105.4) months. The 3-year overall cosmetic deterioration rate was 3.5%. The rates of grade 2 radiation dermatitis and breast induration was 5.8% and 1.5%, respectively. No one experienced ≥ grade 2 breast pain, edema, or telangiectasia. The 5-year cumulative incidence of IBTR and RR was 0.5%. No one developed DM. The 5-year DFS was 99.0%. Four patients died from non-breast cancer causes, and the 5- year OS was 97.9%. In conclusion, we observed lower rates of cosmetic deterioration, IBTR, and ≥ grade 2 acute/late normal tissue effects following PBI with a moderately hypofractionated regimen delivered with IMRT technique. Therefore, this regimen represents an attractive option when an external beam PBI approach is chosen to treat a patient with low-risk early breast cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: We analyzed the distribution of metastatic sites and survival of lung cancer patients with metastases based on hospital registration to provide real-world data support for the treatment and survival management of lung cancer patients. Methods: A total of 1 490 lung cancer patients who developed metastasis during the follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were enrolled in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The effects of age at diagnosis, gender and histological subtype on the distribution of metastases were studied. The Kaplan-Meier method was used to evaluate the overall survival (OS) rates of different metastatic sites. Results: The median follow-up time was 40.8 months. During the follow-up period, 937 cases died from all causes. 67.7% of patients only had single-site metastasis, while 32.3% of patients had multiple-site metastases. The common metastatic sites were bone (33.8%), brain (33.6%), lung (22.8%), liver (12.0%) and adrenal gland (3.7%). Female patients had more metastases to brain (37.8% vs 31.4%). Younger patients were more likely to develop multiple-site metastases, and small cell carcinomas patients had more brain metastases (47.2%) and liver metastases (20.9%). Lung metastasis featured relatively best survival (1-year OS rate: 78.3%, 3-year OS rate: 47.1%, 5-year OS rate: 29.5%), whereas liver metastasis had relatively the worst prognosis (1-year OS rate: 46.4%, 3-year OS rate: 15.2%, 5-year OS rate: 3.6%). Conclusion: The proportions of bone and brain metastases in lung cancer patients with metastasis are high. The distribution of metastatic sites is associated with gender, age at diagnosis and histological type. The prognosis of patient with different metastatic sites is different. Mechanisms or clinical treatment plans can be studied for different metastatic sites to improve the prognosis of late-stage lung cancer patients in future research.

Inflammatory infiltration of synovial M1 macrophages, high levels of ROS, and NO exacerbate osteoarthritis (OA) progression. The PdZn/CoSA‐NC nanozymes, which are highly ordered PdZn intermetallic nanoparticles loaded with Co single atom N‐doped carbon‐rich in multi‐level pores, in an attempt to serve as SOD and CAT mimicking nanozymes for OA therapy is designed. The PdZn/CoSA‐NC nanozymes' high electron transfer and dual active site sufficient exposure enhances free radical adsorption and lower reaction energies, accelerating SOD‐like, CAT‐like, and GPx‐like catalyzed reactions, outperforming CoSA‐NC and PdZn/NC alone. Furthermore, PdZn/CoSA‐NC nanozymes exhibit favorable biocompatibility, reduce synovial macrophage oxidative stress in OA, alleviate hypoxia, restore mitochondrial function, regulate energy metabolism, increase antioxidant factors, and reduce inflammatory factors, thus effectively mitigating the progression of OA. Mechanistically, PdZn/CoSA‐NC nanozymes downregulate M1‐type phenotypic markers like IL‐1β by regulating purine metabolism. The PdZn/CoSA‐NC nanozymes offer a novel approach to treating oxidative stress‐related inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Metastasis remains the cause of 90% of death from cancer. By analyzing the distribution of metastatic sites and survival status of 20 000 metastatic cancer patients from a hospital-based cancer registry database, this study provides the real-world data for the cancer treatment and survival management in China. Methods: A total of 20 067 cancer patients who were diagnosed as having metastatic caner or developed metastasis during the follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The first follow-up date was the diagnosis date of metastasis, and the last follow-up date was November 1, 2020. Kaplan-Meier method was applied in evaluating the 1-, 3- and 5-year overall survival (OS) rates for overall cancer and site-specific cancer patients. Results: The median follow-up time was 46.7 months, 13 170 cases died during the follow- up, 60.05% was single-site metastasis, and 39.95% was multiple-site metastasis. Among all metastable sites, the proportion of metastasis to liver was 33.82%, 26.25% to lung, 26.22% to bone, and 9.22% to brain. The incidence of brain metastasis was the highest in lung cancer patients among all cancer types (31.14%). Liver was the most frequent metastatic site in pancreatic cancer (77.85%), and bone was the most frequent metastatic site in patients with prostate cancer (83.20%). Subgroup analysis showed that liver metastasis was easier to be observed in males than in females (35.46% vs 31.89%, P

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi‐omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro‐inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti‐PD‐1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real‐world and several public immunotherapy cohorts. In summary, S100A5 shapes a non‐inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro‐inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA. [ABSTRACT FROM AUTHOR]

Benign prostate hyperplasia (BPH) is the most commonly seen disease among aging males. Transforming growth factor(TGF)‐β‐mediated epithelial–mesenchymal transition (EMT) and epithelial overproliferation might be central events in BPH etiology and pathophysiology. In the present study, long noncoding RNA MIR663AHG, miR‐765, and FOXK1 formed a competing endogenous RNAs network, modulating TGF‐β‐mediated EMT and epithelial overproliferation in BPH‐1 cells. miR‐765 expression was downregulated in TGF‐β‐stimulated BPH‐1 cells; miR‐765 overexpression ameliorated TGF‐β‐mediated EMT and epithelial overproliferation in BPH‐1 cells. MIR663AHG directly targeted miR‐765 and negatively regulated miR‐765; MIR663AHG knockdown also attenuated TGF‐β‐induced EMT and epithelial overproliferation in BPH‐1 cells, whereas miR‐765 inhibition attenuated MIR663AHG knockdown effects on TGF‐β‐stimulated BPH‐1 cells. miR‐765 directly targeted FOXK1 and negatively regulated FOXK1. FOXK1 knockdown attenuated TGF‐β‐induced EMT and epithelial overproliferation and promoted autophagy in BPH‐1 cells, and partially attenuated miR‐765 inhibition effects on TGF‐β‐stimulated BPH‐1 cells. In conclusion, this study provides a MIR663AHG/miR‐765/FOXK1 axis modulating TGF‐β‐induced epithelial proliferation and EMT, which might exert an underlying effect on BPH development and act as therapeutic targets for BPH treatment regimens. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), as part of the cellular secretome, have emerged as essential cell–cell communication regulators in multiple physiological and pathological processes. Previous studies have widely reported that mesenchymal stromal cell-derived EVs (MSC-EVs) have potential therapeutic applications in ischemic diseases or regenerative medicine by accelerating angiogenesis. MSC-EVs also exert beneficial effects on other vasculopathies, including atherosclerosis, aneurysm, vascular restenosis, vascular calcification, vascular leakage, pulmonary hypertension, and diabetic retinopathy. Consequently, the potential of MSC-EVs in regulating vascular homeostasis is attracting increasing interest. In addition to native or naked MSC-EVs, modified MSC-EVs and appropriate biomaterials for delivering MSC-EVs can be introduced to this area to further promote their therapeutic applications. Herein, we outline the functional roles of MSC-EVs in different vasculopathies and angiogenesis to elucidate how MSC-EVs contribute to maintaining vascular system homeostasis. We also discuss the current strategies to optimize their therapeutic effects, which depend on the superior bioactivity, high yield, efficient delivery, and controlled release of MSC-EVs to the desired regions, as well as the challenges that need to be overcome to allow their broad clinical translation. [ABSTRACT FROM AUTHOR]