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Summary: Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up. Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1–14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051). Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1–39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6–14.6) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6–33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0–15.8) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy. Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.

The failure mechanism of square lithium iron phosphate battery cells under vibration conditions was investigated in this study, elucidating the impact of vibration on their internal structure and safety performance using high-resolution industrial CT scanning technology. Various vibration states, including sinusoidal, random, and classical impact modes, were tested to simulate real-world usage scenarios. The findings demonstrate that different vibration conditions exert varying degrees of influence on the battery cells. Despite experiencing slight deformation and displacement after exposure to vibrations, their overall performance remains stable, with no significant safety hazards detected. Moreover, it was observed that while the side gap increases due to the partial absorption of impact load by both the battery cells and connection components, the bottom gap remains unchanged. This study holds immense significance in enhancing electric vehicle safety and reliability, while providing a scientific foundation for future optimization designs of lithium iron phosphate batteries.

Abstract The role of pyrotinib in the treatment of HER2-positive metastatic breast cancer (MBC) has been well-established. This multicenter, single-arm phase II trial (NCT03876587) aimed to assess the benefit of pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC. Women with HER2-positive MBC who had not undergone HER2 blockade or chemotherapy for metastatic disease were enrolled in the study and received daily oral pyrotinib 400 mg plus intravenous docetaxel 75 mg/m2 every 3 weeks. The primary endpoint was the objective response rate (ORR), secondary endpoints included progression-free survival (PFS), duration of response (DoR), clinical benefit rate (CBR), overall survival (OS) and safety. From June 2019 to June 2021, 79 patients were enrolled. The confirmed ORR was 79.7% (95% confidence interval [CI], 70.8-88.6), and the CBR was 87.3% (95%CI, 80.0-94.6) in the intention-to-treat population. The pre-specified primary endpoint was met. The median DoR was 15.9 months (interquartile range, 8.3-19.5); the median PFS was 16.0 months (95% CI, 11.2-20.8), and the median OS was not reached. The most common grade ≥3 treatment-related adverse events observed were leukopenia (29.1%), neutropenia (27.8%), and diarrhea (21.5%). This study demonstrates that pyrotinib plus docetaxel show an acceptable safety profile and promising antitumor activity as a first-line treatment option for patients with HER2-positive MBC.

Abstract Recurrent fusions of receptor tyrosine kinases (RTKs) are often driving events in tumorigenesis that carry important diagnostic value and are potentially targetable by the increasing number of tyrosine kinase inhibitors (TKIs). Here, we characterized the spectrum of 1324 RTK fusions with intact kinase domains in solid tumors by DNA-based high-throughput sequencing. Overall, the prevalence of RTK fusions were 4.7%, with variable frequencies and diverse genomic structures and fusion partners across cancer types. Cancer types, such as thyroid cancers, urological cancers and neuroendocrine tumors are selective in the RTK fusions they carry, while others exhibit highly complex spectra of fusion events. Notably, most RTKs were promiscuous in terms of the partner genes they recombine with. A large proportion of RTK fusions had one of the breakpoints localized to intergenic regions. Comprehensive genomic profiling revealed differences in co-mutational patterns pre- and post-TKI treatments across various RTK fusions. At baseline, multiple cases were detected with co-occurring RTK fusions or concomitant oncogenic mutations in driver genes, such as KRAS and EGFR. Following TKI resistance, we observed differences in potential on- and off-target resistance mutations among fusion variants. For example, the EML4-ALK v3 variant displayed more complex on-target resistance mechanisms, which might explain the reduced survival outcome compared with the v1 variant. Finally, we identified two lung cancer patients with MET+ and NTRK1+ tumors, respectively, who responded well to crizotinib treatment. Taken together, our findings demonstrate the diagnostic and prognostic values of screening for RTK fusions using DNA-based sequencing in solid tumors.

This study aimed to determine the dormancy type of Chinese olive seeds and improve their germination rate. The water permeability and germination-inhibiting substances of Chinese olive seeds were assessed. Low-temperature stratification and soaking in a GA3 solution were implemented to measure the time lag, initial time, germination rate, and germination potential of the seeds. The findings revealed that the seed coat exhibited poor water permeability, which negatively influenced the germination rate. Additionally, Chinese olive seeds contained substances that inhibited germination. The duration of low-temperature stratification (at 4 ± 1 °C) gradually diminished the dormancy of Chinese olive seeds, resulting in early and rapid germination. The germination rate significantly increased, with the percentage of seed germination rising from 0% to 42.33% within 60 days of stratification. Furthermore, combining low-temperature stratification with different concentrations of GA3 notably enhanced the germination rate. The optimal concentrations of gibberellins for 40 and 60 days of stratification were determined to be 300 and 100 mg/L, respectively. These results indicate that Chinese olive seeds possess non-deep physiological dormancy.

Background and ObjectiveImmune checkpoint inhibitor (ICI)-associated myocarditis is a fatal immune-related adverse events (irAEs), which is prone to affecting multiple organ systems. Multi-organ irAEs have not been fully studied in ICI-associated myocarditis. Therefore, we aimed to explore the impact of multi-organ irAEs on ICI myocarditis in terms of clinical features, treatment, and prognosis.MethodsThis was a retrospective study. The clinical data of ICI myocarditis patients were collected from 6 hospitals in China. The risk factors and characteristics of pure myocarditis and multi-organ irAEs were analyzed. The overall survival (OS) after myocarditis was analyzed and univariate and multivariate regression analysis were performed.ResultsA total of 46 patients were analyzed in this study. Multi-organ irAEs were common (30/46, 65.2%) and prone to severe heart failure. The severe myocarditis was observed in 32 patients (69.6%). When myocarditis occurred, neutrophil to lymphocyte ratio, C-reactive protein, lactate dehydrogenase, interleukin (IL)-6, IL-10, creatine kinase, MB isoenzyme of creatine kinase, and brain natriuretic peptide increased from baseline, but absolute lymphocyte count decreased. Thymoma (B2/B3) was a risk factor for multi-organ irAEs. Heart failure and myocarditis were more severe in patients with multi-organ irAEs and require early corticosteroid therapy (

Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor‐associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR‐195 was reported to be hypermethylated at its promoter CpG island and down‐regulated in hepatocellular carcinoma. However, the function of miR‐195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down‐regulation of microRNA‐195 (miR‐195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR‐195 significantly suppressed cell proliferation, migration, invasion and epithelial–mesenchymal transition (increased E‐cadherin and decreased N‐cadherin) in PCa cells. We further demonstrated that transfection with a miR‐195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5‐azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR‐195 may function as a crucial tumor suppressor in PCa.

BackgroundRecent data on first-line treatment patterns administered to hormone receptor-positive (HR+) advanced breast cancer (ABC) patients in the real-world setting are limited. This study aimed to report the first-line treatment patterns and outcomes of HR+ ABC patients in China.MethodsThis was a multicenter, noninterventional study. Eligible patients were cytologically or histologically confirmed to have HR+ ABC with ≥2 complete medical records and received first-line therapies between January 2015 and June 2019. Treatment patterns and outcomes were extracted from structured or unstructured electronic medical records. Progression-free survival (PFS) was analyzed with the Kaplan-Meier method.ResultsIn total, 1072 patients with HR+ ABC were enrolled at 6 treatment sites: 327 human epidermal growth factor receptor 2-positive (HER2+) patients, 696 HER2-negative (HER2-) patients and 49 HER2-unknown patients. Overall, 62.41% of patients received first-line chemotherapy (CT), 21.08% received targeted therapy (TT) and 15.49% received endocrine therapy (ET). For HR+/HER2+ patients, 65.14% received TT, 28.44% received CT, and 5.81% received ET. Compared with patients who received TT, patients who received CT alone, had a significantly worse median PFS (adjusted hazard ratio [HR] =2.59, 95% confidence interval [CI], 1.64-4.10, p

Metastases typically develop before diagnosis and during the treatment of colorectal cancers, while patients with metastatic colorectal cancers (mCRCs) currently have a poor prognosis. In terms of surgical approaches, adjuvant therapies, and targeted therapies, the treatment of mCRCs has had numerous recent advances. As a targeted agent widely used in mCRCs, cetuximab-based treatment is still under dispute due to its side effects and unstable effect. We present two mCRC cases treated with cetuximab-based therapy, of which two patients achieved complete response and without recurrence for over 22 and 84 months, respectively. To better understand the drug usage, we also reviewed the recent achievements and usage precautions of cetuximab in mCRCs. Present and many previous observations support that cetuximab might be a referred drug in the first-line chemotherapy of mCRCs with wild-type RAS and BRAF and proficient mismatch repair.

Objective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells.Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group.Results: Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient’s prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1.Conclusion: ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.

Abstract Background Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. Methods Refractory metastatic breast cancer patients who have received molecular screening using next‐generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression‐free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. Results A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48‐8.81; P = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group (P = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively (P = .000). The incidence of grade 3‐5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). Conclusions Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off‐label use in clinical practice.

Abstract Background One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. Methods Targeted next‐generation sequencing (NGS) of 416 cancer‐relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2‐ BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. Results In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2‐targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2‐ BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. Conclusions In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2‐ BC patients, respectively.

BACKGROUND:Mucinous breast carcinoma (MC) is a special type of breast cancer that presents with a large amount of extracellular mucin. MC comprises approximately 4% of all invasive breast cancers. This type of tumor has a better prognosis and higher incidence in peri- and post-menopausal patients. Pathologically, there are two main subtypes of MC: pure and mixed. In this study, we describe 10 years of experience with MC at the Zhejiang Cancer Hospital in China, specifically, clinical data, histological findings and immunohistochemical features. METHODS:We identified MC patients who were diagnosed as operable and completed clinical treatment from January 2001 to January 2011. The clinicopathological data included the age at diagnosis, tumor size, TNM stage, presence and number of lymph node (LN) metastases, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status and p53 expression. If the tumor was defined as mixed mucinous carcinoma (MMC), IHC was performed on a non-mucinous part, such as invasive ductal and lobular cancer. We evaluated the clinical characteristics of all MC patients using chi-square, one-way ANOVA and LSD tests. We also studied the correlations between all of the clinical parameters and LN metastasis in a binary logistic regression analysis. We used ten consecutive years of data that were collected at Zhejiang Cancer Hospital. RESULTS:We identified 48 cases of pure mucinous carcinoma (PMC) and 77 cases of MMC. The 48 PMC cases consisted of 38 PMC-A and 10 PMC-B subtypes. The MMCs were divided into two groups, those with partial mixed mucinous breast carcinoma (pMMC, 58 cases) and those with main mixed mucinous breast carcinoma (mMMC, 19 cases). pMMC was defined by tumors with less than 50% mucinous components, while mMMC was defined by tumors where the mucinous component accounted for 50% to 90% of the tumor. No significant differences in the clinicopathological characteristics were noted between the patients with PMC-A and those with PMC-B. The tumor size was larger in the mMMC than PMC cases (44.84 mm vs. 30.06 mm, p = 0.021). The number of positive LN metastases was greater in pMMC than PMC patients (p = 0.024). The clinical stages were significantly different among the three groups, with the pMMC group having more stage III-IV patients than the other two groups (p = 0.005). The incidence of LN metastasis was also higher in the pMMC cases (pMMC vs. mMMC and PMC, 50% vs. 31.58% and 18.75%, p = 0.003). The PMC patients had much lower p53 expression than the other two groups (PMC vs. pMMC and mMMC, 27.08% vs. 55.17% and 57.89%, p = 0.007). The tumor size (>30mm), p53 expression and less proportion of the mucinous component are associated with risk of LN metastasis. CONCLUSION:Based on the results of this study, we conclude that the tumor size, status of LN metastasis, clinical stage, and p53 mutation rate may differ between MMC and PMC patients. The tumor size (>30mm), p53 mutation and less proportion of the mucinous component should be considered risk factors of LN metastasis in MC patients.

Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study.Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I-II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS).In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002).The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer.

Abstract Improving bus travel time reliability can attract more commuters to use bus transit, and therefore reduces the share of cars and alleviates traffic congestion. This paper formulates a new bus travel time reliability metric that jointly considers two stochastic processes: the in-stop waiting process and in-vehicle travel time process, and the bus travel time reliability function is calculated by the convolution of independent events’ probabilities. The new reliability metric is defined as the probability when bus travel time is less than a certain threshold and can be used in both conditions with and without bus transfer. Next, Automatic Vehicle Location (AVL) data of the city of Harbin is used to demonstrate the applicability of the proposed method. Results show that factors such as weather, day of the week, departure time, travel distance, and the distance from the boarding stop to the bus departure station can significantly affect the travel time reliability. Then, a case with low bus departure frequency is analyzed to show the impact of travelers’ arrival distribution on their bus travel time reliability. Further, it is demonstrated that the travel time reliabilities of two bus transfer schemes of the same Origin–Destination (O–D) pair can have significantly different patterns. Understanding the bus travel time reliability pattern of the alternative bus routes can help passengers to choose a more reliable bus route under different conditions. The proposed bus travel time reliability metric is tested to be sensitive to the effect of different factors and can be applied in bus route recommendation, bus service evaluation, and optimization.

Modeling the relationship between vehicle speed and density on the road is a fundamental problem in traffic flow theory. Recent research found that using the least-squares (LS) method to calibrate single-regime speed-density models is biased because of the uneven distribution of samples. This paper explains the issue of the LS method from a statistical perspective: the biased calibration is caused by the correlations/dependencies in regression residuals. Based on this explanation, we propose a new calibration method for single-regime speed-density models by modeling the covariance of residuals via a zero-mean Gaussian Process (GP). Our approach can be viewed as a generalized least-squares (GLS) method with a specific covariance structure (i.e., kernel function) and is a generalization of the existing LS and the weighted least-squares (WLS) methods. Next, we use a sparse approximation to address the scalability issue of GPs and apply a Markov chain Monte Carlo (MCMC) sampling scheme to obtain the posterior distributions of the parameters for speed-density models and the hyperparameters (i.e., length scale and variance) of the GP kernel. Finally, we calibrate six well-known single-regime speed-density models with the proposed method. Results show that the proposed GP-based methods (1) significantly reduce the biases in the LS calibration, (2) achieve a similar effect as the WLS method, (3) can be used as a non-parametric speed-density model, and (4) provide a Bayesian solution to estimate posterior distributions of parameters and speed-density functions.

Metro systems in megacities such as Beijing, Shenzhen, and Guangzhou are under great passenger demand pressure. During peak hours, it is common to see oversaturated conditions (i.e., passenger demand exceeds network capacity) and a popular control intervention is to restrict the entering rate by setting up out-of-station queueing with crowd control barriers. The out-of-station waiting can make up a substantial proportion of total travel time but is often ignored in the literature. Quantifying out-of-station waiting is important to evaluating the social benefit and cost of metro services; however, out-of-station waiting is difficult to estimate because it leaves no trace in smart card transactions of metros. In this study, we estimate the out-of-station waiting time by leveraging the information from a small group of transfer passengers—those who transfer from nearby bus routes to the metro station. Based on the transfer interval of this small group, we infer the out-of-station waiting time for all passengers by a Gaussian Process regression and then use the estimated out-of-station waiting time to build queueing diagrams. We apply our method to the Tiantongyuan North station of Beijing metro; results show that the maximum out-of-station waiting time can reach 15 ​min, and the maximum queue length can be over 3000 passengers. We find out-of-station waiting can cause significant travel costs and thus should be considered in analyzing transit performance, mode choice, and social benefits. To the best of our knowledge, this paper is the first quantitative study for out-of-station waiting time.

Background: Recent studies have established non-coding RNAs, which include microRNAs and lncRNAs, are aberrantly expressed in breast cancer. In this study, we explore the expression profile of microRNAs and lncRNAs in ER positive (ER+) breast and paracancerous tissues and define their possible correlations. Methods: We collected ER+ breast cancer patients' and paracancerous tissues from the specimen bank of Zhejiang Cancer Hospital to extract total RNA for obtaining the expression level of microRNAs and lncRNAs by qRT-PCR. Results: The relative expression results indicated that microRNAs such as MIR-191, MIR-213, MIR-122A had significantly higher expression and MIR-125B-1, MIR-125B-2, MIR-145 had lower expression in ER positive breast cancer compared to normal breast. The interaction of microRNA and lncRNA results exhibited up-regulated MIR382-5P and lncRNA 362 in ER+ breast cancer compared to non-cancerous breast. By contrast, MIR222 and NFIA-AS1 are down-regulated. Furthermore, MIR222 and NFIA-AS1 showed different expressions in different TNM stages. Conclusions: MicroRNAs and lncRNAs are aberrantly expressed in ER+ breast cancer. It is inferred that these microRNAs and lncRNAs may be promising biomarkers for ER positive breast cancer. [ABSTRACT FROM AUTHOR]

It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the CYP19A1 rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of CYP19A1 rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for CYP19A1 rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment. [ABSTRACT FROM AUTHOR]

The aim of the present study was to establish the underlying regulatory mechanism of estrogen receptor (ER) in breast cancer cell gene expression. A gene expression profile (accession no. GSE11324) was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from an estrogen treatment group and a control group were identified. Chromatin immunoprecipitation with high-throughput sequencing data (series GSE25710) was obtained from the GEO for the ER binding sites, and binding and expression target analysis was performed. A total of 3,122 DEGs were obtained and ER was demonstrated to exhibit inhibition and activation roles during the regulation of its target gene expression. Motif analysis revealed that the upregulated target genes that demonstrated interactions with ER were meis homeobox 1 (MEIS1) and forkhead box P3 (FOXP3). The downregulated target genes, which demonstrated interactions with ER, were thyroid hormone receptor, ß (THRB) and grainyhead-like 1 (GRHL1). Thus, it was observed that ER stimulated gene expression by interacting with MEIS1 and FOXP3, and ER inhibited gene expression by interacting with THRB and GRHL1. However, additional experiments are required to provide further confirmation of these findings. [ABSTRACT FROM AUTHOR]

Exploring the relationship between the tourism carbon environment and high-quality economic development in the Yellow River Basin is a national strategy to meet the realistic requirements of the goal of “Carbon Peak and Carbon Neutral”. It is also conducive to the realization of “Ecological Protection and High-quality Development Strategy in the Yellow River Basin”. Therefore, based on the calculation of tourism’s carbon emission efficiency and the evaluation of the tourism economy’s high-quality development, the interaction mechanism between them was observed. The results showed that, firstly, the tourism carbon emission efficiency of the Yellow River Basin increased slightly from 2010 to 2019, with an average of 0.9782, which was at a medium efficiency level. Secondly, the tourism economy’s high-quality development level is rising, and the speed of development is fast, especially in western provinces. Thirdly, there is a parasitic relationship between the two, but in each province, there is a positive or negative asymmetric symbiotic relationship. The tourism economy’s high-quality development has a greater impact on the efficiency of tourism’s carbon emissions. Fourthly, energy and capital input, as well as coordination and innovation factors, are important driving factors of the symbiosis between the two, among which the role of labor input was gradually revealed, and the impact factor experienced the changing process of “sharing-coordination-innovation”. This study provides a theoretical framework and evaluation methods for evaluating and analyzing the relationship between tourism’s carbon emission efficiency and the tourism economy’s high-quality development, and it provides data support and policy suggestions for the real development.

The aim of the present study was to investigate the immunohistochemical expression of cluster of differentiation (CD) 34 and vascular endothelial growth factor (VEGF) in breast cancer tissue, and their prognostic significance. High CD34 expression levels (microvessel density, >15/HPF) were identified in 27.3% (12/44) of cases, exhibiting no significant correlation with the clinicopathological characteristics of the patients. However, Kaplan-Meier analysis demonstrated that the survival time of patients with high CD34 expression was significantly shorter than that of patients with low CD34 expression (50.0 vs. 90.6%; P=0.003). Samples with high VEGF expression levels (++ or +++) accounted for 63.6% (28/44) of the total number of cases. High VEGF expression was significantly prevalent in patients aged ≥50 years compared with patients aged <50 years (≤78.6 vs. 37.5%; P=0.006). Furthermore, all patients with vascular invasion exhibited high VEGF expression levels; thus, patients with vascular invasion presented with significantly higher VEGF expression rates compared with patients with no vascular invasion (100.0 vs. 55.6%; P=0.018). However, Kaplan-Meier analysis demonstrated that high VEGF expression was not correlated with the overall survival of the patients (P=0.366). By contrast, Cox multivariate analysis identified that clinical stage, triple-negative subtype and age were independent prognostic factors for patients with breast cancer (P=0.005, P=0.006 and P=0.032, respectively), and that CD34 expression was a potential independent prognostic factor (P=0.055). Therefore, the present study determined that for patients with breast cancer, a high level of CD34 expression may be a potential indicator of a poor prognosis. [ABSTRACT FROM AUTHOR]

Context: Breast cancer becomes more prevalent with advancing age. The increased risk of breast cancer needs to be considered when choosing a treatment plan and a kind of detection method for the postmenopausal woman. Better breast cancer prognostication may improve selection of patients for adjuvant therapy. Aims: The aim of this study is to investigate the role of serum protein peak 3144 m/z in postmenopausal breast cancer patients, whether if it could be used as a potential prognostic tool. Settings and Design: Two hundred and two postmenopausal breast cancer patients were involved in this retrospective study at Zhejiang Cancer Hospital. Subjects and Methods: Serum level of protein peak 3144 m/z was assessed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Statistical Analysis Used: Prognostic factors were compared across subgroups of patients depending on the protein peak 3144 m/z levels by Chi-square test. The log-rank test was used to compare survival curves, and Cox proportional hazards regression analysis was performed to identify prognostic factors. Results: The percentage of cases with higher 3144 m/z protein peak was 32.7% (66/202) in postmenopausal breast cancer patients. The serum protein peak 3144 m/z was positively related to lymph node metastasis. Patients with higher protein peak 3144 m/z had significantly poorer overall survival compared with patients with lower serum protein peak 3144 m/z (P = 0.0053). Multivariate regression analysis also revealed that protein peak 3144 m/z was an independent prognostic factor in postmenopausal breast cancer patients (borderline, P = 0.064). Conclusions: The protein peak 3144 m/z was a potential prognostic factor, and it could be used as a prognostic monitoring tool in postmenopausal breast cancer patients. [ABSTRACT FROM AUTHOR]