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Abstract Gastrointestinal (GI) cancers (gastric cancer, oesophageal cancer, liver cancer, colorectal cancer, etc.) are the most common cancers with the highest morbidity and mortality in the world. The therapy for most GI cancers is difficult and is associated with a poor prognosis. In China, upper GI cancers, mainly gastric cancer (GC) and oesophageal cancer (EC), are very common due to Chinese people’s characteristics, and more than half of patients are diagnosed with distant metastatic or locally advanced disease. Compared to other solid cancers, such as lung cancer and breast cancer, personalized therapies, especially targeted therapy and immunotherapy, in GC and EC are relatively lacking, leading to poor prognosis. For a long time, most studies were carried out by using in vitro cancer cell lines or in vivo cell line-derived xenograft models, which are unable to reproduce the characteristics of tumours derived from patients, leading to the possible misguidance of subsequent clinical validation. The patient-derived models represented by patient-derived organoid (PDO) and xenograft (PDX) models, known for their high preservation of patient tumour features, have emerged as a very popular platform that has been widely used in numerous studies, especially in the research and development of antitumour drugs and personalized medicine. Herein, based on some of the available published literature, we review the research and application status of PDO and PDX models in GC and EC, as well as detail their future challenges and prospects, to promote their use in basic and translational studies or personalized therapy.

Abstract Background The efficacy of breast reconstruction for patients with N2‐3M0 stage female breast cancer (FBC) remained unclear due to the lack of randomized clinical trials. This retrospective study aimed to explore the efficacy of breast reconstruction for patients with N2‐3M0 stage FBC. Methods Two thousand five hundred forty‐five subjects with FBC staged by N2‐3M0 from 2010 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results database. Generalized boosted model (GBM) and propensity score matching (PSM) analyses and multivariable Cox analyses were employed to assess the clinical prognostic effect of postmastectomy reconstruction for patients with N2‐3M0 stage FBC in breast cancer‐specific survival (BCSS). Results Totally, 1784 candidates underwent mastectomy alone (mastectomy group), and 761 candidates underwent postmastectomy reconstruction (PMbR group), with 418 breast‐specific deaths after a median follow‐up time of 57 months (ranging from 7 to 227 months). BCSS in the mastectomy group showed no statistical difference from that in the PMbR group in the PSM cohort (HR = 0.93, 95% CI: 0.70–1.25, p = 0.400) and GBM cohort (HR = 0.75, 95% CI: 0.56–1.01, p = 0.057). In the multivariate analyses, there was no difference in the effect of PMbR and mastectomy on BCSS in the original cohort (HR = 0.85, 95% CI: 0.66–1.09, p = 0.197), PSM cohort (HR = 0.86, 95% CI: 0.64–1.15, p = 0.310), and GBM cohort (HR = 0.84, 95% CI: 0.61–1.17, p = 0.298). Triple‐negative breast cancer (TNBC) was a detrimental factor affecting BCSS for patients in the PMbR group. Conclusions Our study demonstrated that PMbR is an oncologically safe surgical treatment and can be widely recommended in clinics for females with non‐TNBC staged by T0‐3N2‐3M0.

Abstract Unsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97–13.52) per 100,000 people and 570.78 (95% UI: 510.24–658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62–9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82–533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90–3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52–119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08–0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51–25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40–44 age group for men and the 35–39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.

The non-point source (NPS) pollution has become an important limitation to the sustainable development of the Three Gorges Reservoir Area (TGRA) water resources. NPS load estimation research has theoretical and realistic significance for water environment security and water pollution control. Therefore, the TGRA was chosen to be the study area, and the export coefficients of different land-use type were calculated through literature consultation method combined with improved observation experiment. The load of total nitrogen (TN) and total phosphorus (TP) of NPS from different pollution sources including farmland, decentralized livestock and poultry breeding and domestic pollution sources were estimated. The results are shown as follows: the order of TN load of different sources in the TGRA from high to low was land use, livestock and poultry breeding, rural life; the TN from land use was 372% higher than that of rural; the order of TP load of different sources in the TGRA from high to low was livestock and poultry breeding, rural life, land use; the TP from livestock and poultry breeding was 114.5% higher than that of land use. Therefore, control of livestock and poultry sewage discharges was the key practice to limit the TP loss, while the optimization of agricultural management was the key practice to control the loss of TN. HIGHLIGHTS In this study, the TN and TP loads of NPS pollution of TGRA based on ECM in 2010 were estimated.; The export coefficients of different sources were determined by field observation and literature consultation.;

Background: Radiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size. Methods: The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010–2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan–Meier, X-tile, Cox proportional hazards model and competing risk model. Results: A total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors. Conclusion: Small tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.

BackgroundResearch on the incidence, mortality, and disability-adjusted life years (DALYs) of female breast and gynecologic cancers (FeBGCs) and the relevant risk factors for adolescents and young adults (AYAs) are valuable for policy-making in China. We aimed to estimate the incidence, deaths, and DALYs and predict epidemiological trends of FeBGCs among AYAs in China between 1990 and 2019.MethodsData from the 2019 Global Burden of Disease (GBD) study between 1990 and 2019 in 195 countries and territories were retrieved. Data about the number of FeBGC incident cases, deaths, DALYs, age-standardized rates (ASRs), and estimated annual percentage changes (EAPCs) were extracted. A comparative risk assessment framework was performed to estimate the risk factors attributable to breast cancer deaths and DALYs, and autoregressive integrated moving average (ARIMA) models were fitted for time-series analysis to predict female cancer morbidity and mortality among Chinese AYAs until 2030.ResultsIn 2019, there are 61,038 incidence cases, 8,944 deaths, and 529,380 DALYs of FeBGCs among the AYAs in China, respectively. The estimated annual percentage change (EAPC) values were positive scores (>0) in ASIRs and negative scores (

BackgroundDue to the loss of prediction of overall survival (OS) for patients with invasive micropapillary carcinoma (IMPC) after breast-conserving surgery (BCS), this study aimed to construct a nomogram for predicting OS in IMPC patients after BCS.MethodsIn total, 481 eligible cases staged 0-III IMPC from 2000 to 2016 were retrieved from the SEER database. A nomogram was built based on the variables selected by LASSO regression to predict the 3-year and 5-year probabilities of OS.ResultsA total of 336 patients were randomly assigned to the training cohort and 145 cases in the validation cohort. The LASSO regression revealed that six variables (age at diagnosis, AJCC stage, marital status, ER status, PR status, and chemotherapy) were predictive variables of OS, and then a nomogram model and an easy-to-use online tool were constructed. The C-indices 0.771 in the training cohort and 0.715 in the validation cohort suggested the robustness of the model. The AUC values for 3-year and 5-year OS in the training cohort were 0.782, 0.790, and 0.674, and 0.682 in the validation cohort, respectively. Based on the cutoff values of 147.23 and 222.44 scores calculated by X-tile analysis, participants in the low-risk group (≤147.23 scores) had a more favorable OS in comparison with those in the medium (>147.23, but

IntroductionDue to the lack of randomized controlled trial, the effectiveness and oncological safety of nipple-excising breast-conserving therapy (NE-BCT) for female breast cancer (FBC) remains unclear. We aimed to explore and investigate the prognostic value of NE-BCT versus nipple-sparing breast-conserving therapy (NS-BCT) for patients with early FBC.MethodsIn this cohort study, data between NE-BCT and NS-BCT groups of 276,661 patients diagnosed with tumor–node–metastasis (TNM) stage 0–III FBC from 1998 to 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching analysis, Kaplan–Meier, X-tile, Cox proportional hazards model, and competing risk model were performed to evaluate the effectiveness and oncological safety for patients in NE-BCT and NS-BCT groups.ResultsA total of 1,731 (0.63%) patients received NE-BCT (NE-BCT group) and 274,930 (99.37%) patients received NS-BCT (NS-BCT group); 44,070 subjects died after a median follow-up time of 77 months (ranging from 1 to 227 months). In the propensity score matching (PSM) cohort, NE-BCT was found to be an adversely independent prognostic factor affecting overall survival (OS) [hazard ratio (HR), 1.24; 95% CI, 1.06–1.45, p=0.0078]. Subjects in NE-BCT group had similar breast-cancer-specific survival (BCSS) (HR, 1.15; 95%CI, 0.88–1.52, p=0.30) and worse other-causes-specific death (OCSD) (HR, 1.217; 95%CI, 1.002–1.478, p=0.048

BackgroundMarital status is an important foundation of social public relations in modern society, but little is known about the role of marriage status among women who underwent breast reconstruction following mastectomy. This research mainly aimed to investigate the prognostic value of marital status in breast cancer women who underwent breast reconstruction.MethodsThe demographic and clinical data of patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program database. The eligible population was assessed on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) through propensity score matching (PSM) method, multivariate Cox proportional hazards model analysis, competing risk model analysis, multivariate competing risk regression model analysis, and subgroup analysis.ResultsOf the 54,683 women included in the current study, a total of 38,110 participants were married patients (married group), and 16,573 participants were unmarried patients (unmarried group). Patients in the married group tended to have better OS (hazard ratio [HR] = 1.397, 95% CI: 1.319–1.479, p < 0.001), BCSS (HR = 1.332, 95% CI: 1.244–1.426, p < 0.001), cumulative BCSD incidence (Gray's test, p < 0.001), and other causes-specific death (OCSD) incidence (Gray's test, p < 0.001) than those in the unmarried group. In subgroup analysis, subjects with HR+/HER2– subtype breast cancer in the married group showed improved OS (1.589, 95% CI: 1.363–1.854, p < 0.001) and BCSS (HR = 1.512, 95% CI: 1.255–1.82, p < 0.001) than those in the unmarried group.ConclusionsOur study demonstrated that the inexistence of marriage was associated with poorer OS and BCSS, especially for HR+/HER2– breast cancer women who underwent breast reconstruction.

PurposeDue to the rarity of metaplastic breast carcinoma (MpBC), no randomized trials have investigated the role of combined chemotherapy and radiotherapy (CCRP) in this condition. We aimed to explore and identify the effectiveness of CCRP in patients with regional lymph node metastasis (N+) non-metastatic MpBC.Materials and MethodsData were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database. We assessed the effects of CCRP on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) using Kaplan-Meier analysis, competing risk model analysis, and competing risk regression mode analysis.ResultsA total of 707 women and 361 death cases were included in the unmatched cohort, of which 76.45% (276/361) were BCSD, and 23.55% (85/361) were non-breast cancer-specific deaths (non-BCSD). Both the ChemT and CCRP groups had better OS (ChemT group: HR: 0.59, 95% CI: 0.45–0.78, P

Four new metabolites, asperchalasine I (1), dibefurin B (2) and two epicoccine derivatives (3 and 4), together with seven known compounds (5−11) were isolated from a mangrove fungus Mycosphaerella sp. SYSU-DZG01. The structures of compounds 1−4 were established from extensive spectroscopic data and HRESIMS analysis. The absolute configuration of 1 was deduced by comparison of ECD data with that of a known structure. The stereostructures of 2−4 were further confirmed by single-crystal X-ray diffraction. Compounds 1, 8 and 9 exhibited significant α-glucosidase inhibitory activity with IC50 values of 17.1, 26.7 and 15.7 μM, respectively. Compounds 1, 4, 6 and 8 showed antioxidant activity by scavenging DPPH· with EC50 values ranging from 16.3 to 85.8 μM.