Survival and Trends in Annualized Hazard Function by Age at Diagnosis Among Chinese Breast Cancer Patients Aged ≤40 Years: Case Analysis Study.

BACKGROUND: Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. OBJECTIVE: We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. METHODS: The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as end points. RESULTS: We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P<.001), 5-year DMFS (P<.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality. CONCLUSIONS: The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC.

Dysregulated MAPK signaling pathway in acute myeloid leukemia with RUNX1 mutations.

BACKGROUND: Acute myeloid leukemia (AML) is a hematologic malignancy with genetic alterations. RUNX1, which is an essential transcription factor for hematopoiesis, is frequently mutated in AML. Loss-of-function mutation of RUNX1 is correlated with poor prognosis of AML patients. It is urgent to reveal the underlying mechanism. RESEARCH DESIGN AND METHODS: TCGA AML, GSE106291, GSE142700, and GSE67609 datasets were used. R package was used to define differentially expressed miRNAs, miRNA target genes, RUNX1-related gene, RUNX directly regulating genes, and so on. The relationship of gene expression with overall survival was analyzed by Cox regression. KEGG and GO analyses were applied to the above-mentioned genesets and overlapped genes. Alteration and importance of MAPK pathway were validated in K562 cells by Western blotting and apoptosis assay in vitro. RESULTS: RUNX1 regulated MAPK pathway indirectly and directly. MAPK pathway was altered in K562-cell-induced mutated RUNX1, and these cells were more sensitive to AraC after p38 was inhibited. CONCLUSIONS: RUNX1 could modulate MAPK pathway, which may provide a potential therapeutic target for AML patients with RUNX1 mutations.

Effects of cinnamon supplementation on lipid profiles among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Studies in animals and humans have reported numerous beneficial effects of cinnamon. However, its hypolipidemic efficacy in patients with metabolic syndrome (MetS) and related disorders is still controversial. This meta-analysis aimed to evaluate the lipid-regulating effects and safety of cinnamon in a population with MetS and related disorders. METHODS: Studies that met the inclusion criteria were retrieved from PubMed, Embase, Cochrane Library, and Web of Science. Randomized placebo-controlled trials of cinnamon or its extracts in the treatment of MetS and related metabolic diseases were the main eligibility criteria. The Cochrane Handbook was used to guide the study selection, quality assessment, and data analysis. All statistical analyses were performed using Stata 15.0. RESULTS: Twelve studies involving 773 subjects were included in the meta-analysis. The overall results showed that cinnamon could significantly reduce total cholesterol (weighted mean difference [WMD]: -0.19 mmol/L [-7.34 mg/dL]; 95% confidence interval [CI]: -0.24, -0.14 [-9.27, -5.41]), triglyceride (WMD: -0.10 mmol/L [-8.85 mg/dL]; 95% CI: -0.16, -0.04 [-14.16, -3.54]), and low-density lipoprotein cholesterol (WMD: -0.16 mmol/L [-6.18 mg/dL]; 95% CI: -0.20, -0.11 [-7.72, -4.25]). In the subgroup analysis, cinnamon did not exhibit a significant effect on lipid profiles in European and American patients. Larger doses of cinnamon tended to exhibit better regulation of lipid profiles and high-dose cinnamon (≥1.5 g/d) significantly increased high-density lipoprotein cholesterol (WMD: 0.07 mmol/L [2.70 mg/dL]; 95% CI: 0.03, 0.11 [1.16, 4.25]). CONCLUSION: The current evidence shows that cinnamon can regulate lipid profiles in patients with metabolic disorders.

Case Report: Rare Systemic and Aggressive ALK-Positive Histiocytosis With Recurrent Pancreatitis Treating by Alectinib.

ALK-positive histiocytosis (APH) is a rare and recently described, solitary or generalized, histiocytic proliferative disorder with a characteristic gene translocation involving the fusion of the ALK gene at chromosome 2p23. To date, only 25 cases of APH have been reported. The patient presented with multiple nodules in the lung, liver, gallbladder, pancreas, kidney, and skin rashes, along with recurrent pancreatitis and cholecystitis. The histiocytes from the lesion were positive for CD68 and ALK and negative for S100 and CD1α. A reduced dose of the ALK inhibitor alectinib was administered rather than the standard dose of alectinib or chemotherapy because of recurrent pancreatitis, which has not been previously reported in APH cases. After 18 months of follow-up, the patient was maintained on alectinib, and a partial response (PR) was achieved.

Inhibitory effects of temozolomide on glioma cells is sensitized by RSL3-induced ferroptosis but negatively correlated with expression of ferritin heavy chain 1 and ferritin light chain.

Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temozolomide response of gliomas. However, whether inducing ferroptosis could affect invasive growth of glioblastoma cells and which ferroptosis-related regulators were involved in temozolomide resistance are still unclear. In this study, we treated glioblastoma cells with RSL3, a ferroptosis inducer, in vitro (cell lines) and in vivo (subcutaneous and orthotopic animal models). The treated glioblastoma cells with wild-type or mutant IDH1 were subjected to RNA sequencing for transcriptomic profiling. We then analyze data from our RNA sequencing and public TCGA glioma database to identify ferroptosis-related biomarkers for prediction of prognosis and temozolomide resistance in gliomas. Analysis of transcriptome data from RSL3-treated glioblastoma cells suggested that RSL3 could inhibit glioblastoma cell growth and suppress expression of genes involved in cell cycle. RSL3 effectively reduced mobility of glioblastoma cells through downregulation of critical genes involved in epithelial-mesenchymal transition. Moreover, RSL3 in combination with temozolomide showed suppressive efficacy on glioblastoma cell growth, providing a promising therapeutic strategy for glioblastoma treatment. Although temozolomide attenuated invasion of glioblastoma cells with mutant IDH1 more than those with wild-type IDH1, the combination of RSL3 and temozolomide similarly impaired invasive ability of glioblastoma cells in spite of IDH1 status. Finally, we noticed that both ferritin heavy chain 1 and ferritin light chain predicted unfavorable prognosis of glioma patients and were significantly correlated with mRNA levels of methylguanine methyltransferase as well as temozolomide resistance. Altogether, our study provided rationale for combination of RSL3 with temozolomide to suppress glioblastoma cells and revealed ferritin heavy chain 1 and ferritin light chain as biomarkers to predict prognosis and temozolomide resistance of glioma patients.

Efficacy of artemisinin and its derivatives in animal models of type 2 diabetes mellitus: A systematic review and meta-analysis.

Although current evidence suggests that artemisinin and its derivatives play a multitarget therapeutic role in type 2 diabetes mellitus (T2DM), their efficacy and safety remain under debate. This meta-analysis aimed to evaluate the effects and safety of artemisinin and its derivatives in T2DM animal models. Preclinical studies that met the inclusion criteria were retrieved from PubMed, Embase, Web of Science, Scopus, CINAHL, OpenGrey, Google Scholar, Psyclnfo, British Library Ethos, ProQuest Dissertations & Theses, China National Knowledge Internet, VIP Information Chinese Periodical Service Platform, Chinese Biomedicine Literature Database, and Wanfang Data Knowledge Service Platform. Twenty-two studies involving 526 animals were included in the meta-analysis. The RevMan 5.3 and Stata 15.0, were used to perform the statistical analyses. The overall results showed that artemisinin or its derivatives could significantly reduce fasting plasma glucose, 2-h plasma glucose (2hPG) in the intraperitoneal glucose tolerance test (IPGTT), 2hPG in the intraperitoneal insulin tolerance test (IPITT), glycated hemoglobin A1c, under the curve in the IPGTT/IPITT, total cholesterol, triglyceride, low-density lipoprotein cholesterol, free fatty acid, and urine volume. Although increase in body weight was observed due to administration of the compounds, no significant effect was observed regarding serum insulin. In terms of adverse reactions, only two of the included studies reported that high-dose artemether may cause digestive inhibition in mice. Our results suggest that artemisinins could improve several parameters related to glycolipid metabolism in T2DM animal models. However, to evaluate the antidiabetic effects and safety of artemisinins in a more accurate manner, additional preclinical studies are necessary.

Study on the Mechanisms of Banxia Xiexin Decoction in Treating Diabetic Gastroparesis Based on Network Pharmacology.

In China, Banxia Xiexin decoction (BXD) is applied to treat diabetic gastroparesis (DGP), but its key active ingredients and mechanisms against DGP are unclear. This study is designated to reveal the molecular mechanisms of BXD in treating DGP by adopting a creative approach known as network pharmacology to explore the active ingredients and therapeutic targets of BXD. In our study, 730 differentially expressed genes of DGP were obtained, and 30 potential targets of BXD against DGP were screened out (including ADRB2, DRD1, FOS, MMP9, FOSL1, FOSL2, JUN, MAP2, DRD2, MYC, F3, CDKN1A, IL6, NFKBIA, ICAM1, CCL2, SELE, DUOX2, MGAM, THBD, SERPINE1, ALOX5, CXCL11, CXCL2, CXCL10, RUNX2, CD40LG, C1QB, MCL1, and ADCYAP1). Based on the findings, BXD contains 60 compounds with therapeutic effect on DGP, including the key active ingredients such as quercetin, wogonin, baicalein, beta-sitosterol, and kaempferol. Sixty-eight pathways including TNF signaling pathway, IL-17 signaling pathway, and AGE-RAGE signaling pathway were significantly enriched. In this study, the mechanisms of BXD in treating DGP are affirmed to be a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.

Effect of Fenugreek on vasomotor symptoms in menopausal women: A protocol for systematic review and meta-analysis.

BACKGROUND: Vasomotor symptoms (hot flashes or night sweats) are closely related to the impaired quality of life in menopausal women. Fenugreek is the ripe seed of Trigonella foenum graecum Linn. In China, this plant is used to relieve menopausal symptoms in women. Although recent studies have shown that fenugreek may have a good effect on the menopausal symptoms, there is no meta-analysis to systematically evaluate its efficacy in improving menopausal vasomotor symptoms. METHODS: Randomized controlled trials that met the inclusion criteria will be retrieved in 5 English online databases and 4 Chinese online databases. The primary outcomes are changes in frequency and intensity of vasomotor symptoms that measured by validated scales. The secondary outcomes will include quality of life, blood hormone parameters, blood biochemical parameters, and adverse events. Heterogeneity of data will be assessed by I and Cochrane Q statistics. Sensitivity analysis and subgroup analysis will be performed to explore the sources of heterogeneity. Egger test and Begg test will be used to assess the publication bias. Finally, we will evaluate the quality of evidence by the GRADE approach. All the data statistics will be performed using the STATA 15.0 software. RESULTS: All the results of will be published in a peer-reviewed journal. CONCLUSIONS: This meta-analysis will systematically evaluate the efficacy and safety of fenugreek in the treatment of menopausal vasomotor symptoms. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/3BCY8.

Crizotinib versus chemotherapy: a real-world cost-effectiveness study in China.

Aim: To assess the cost-effectiveness of crizotinib verses platinum-based doublet chemotherapy as the first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in the real-world setting. Methods: Data from 163 advanced ALK positive NSCLC patients were collected from West China Hospital, Sichuan University (Chengdu, China). They were categorized into two groups as treated with crizotinib (n = 83) or chemotherapy (n = 80) as a first-line therapy. The progression-free survival (PFS) as the primary clinical outcome, and the direct medical costs were collected from hospital information systems. Incremental cost-effectiveness ratio (ICER) was calculated with costs, quality-adjusted life-years, as well as the costs discounted at 3% annually. Additionally, two different kinds of medical insurance (MI) for pharma-economic assessment were considered. Results: Crizotinib improved PFS versus chemotherapy in ALK positive patients (median PFS 19.67 m vs 5.47 m; p < 0.001). Moreover, crizotinib obtained an ICER of US$36,285.39 before the end of 2016, when crizotinib, pemetrexed and anti-angiogenesis drugs were not MI covered. This is more than the willingness to pay threshold (three-times of gross domestic product per capita in mainland China or Sichuan Province). However, ICER was US$7321.16, which is less than willingness to pay, when crizotinib and all chemotherapy drugs were covered by MI from the end of 2016. Sensitivity analysis demonstrated a 99.7% probability for crizotinib to be more cost-effective than chemotherapy, when crizotinib and all anticancer drugs were MI covered. One-way sensitivity analysis for the reimbursement ratio of crizotinib indicated that cost-effective tendency for crizotinib increased as reimbursement ratio increased. Conclusion: Crizotinib could be an effective, and cost-effective first-line treatment for ALK positive advanced NSCLC with the MI coverage currently available in Chengdu, Sichuan Province, China.

[Application and development of spectral network cluster method in post-translational modifications of identification peptides].

Mass spectrometry and database searching are necessary to identify proteins and peptides. With the rapid development of mass spectrometry technology, mass spectrometry data in proteomics are acquired very quickly, providing a powerful method to identify large-scale proteins and peptides, making mass spectrometry data-based proteomics research more and more into the mainstream. The traditional database searching method has many limitations to identify post-translational modifications of peptides. This paper systematically reviews the development, theoretical concept and applications of spectral network method, and the advantages of spectral network library to identify peptides.