Two Hematological Markers Predicting the Efficacy and Prognosis of Neoadjuvant Chemotherapy Using Lobaplatin Against Triple-Negative Breast Cancer.

BACKGROUND: Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. METHODS: Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. RESULTS: The tpCR rate in the PLR- group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P = .032). The tpCR rate in the NLR- group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P = .024). The tpCR rate of the PLR-NLR- (PLR- and NLR-) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR- group (P = .028 for EFS; P = .047 for OS). Patients in the PLR-NLR- group had a longer EFS than those in the PLR+/NLR+ group (P = .002). CONCLUSION: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis.

Dysregulation of ferroptosis-related genes in granulosa cells associates with impaired oocyte quality in polycystic ovary syndrome.

Background: Poor oocyte quality remains one of the major challenges for polycystic ovary syndrome (PCOS) patients during in vitro fertilization (IVF) treatment. Granulosa cells (GCs) in PCOS display altered functions and could cause an unfavorable microenvironment for oocyte growth and maturation. Ferroptosis is a new form of programmed cell death, but its role in PCOS has been largely unclarified. Methods: Ferroptosis-related differentially expressed genes (DEGs) of GCs in women with PCOS were identified by bioinformatic analyses of GSE155489 and GSE168404 datasets. Functional enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Core ferroptosis-related genes were further screened by random forest, and evaluated for diagnostic value by receiver operating characteristic curve analyses. Gene expression was validated by real-time quantitative polymerase chain reaction of collected GC samples, and analyzed for association with oocyte quality. In addition, gene regulatory network was constructed based on predicted RNA interactions and transcription factors, while potential therapeutic compounds were screened through molecular docking with crystallographic protein structures. Results: A total of 14 ferroptosis-related DEGs were identified. These DEGs were mainly enriched in reactive oxygen species metabolic process, mitochondrial outer membrane, antioxidant activity as well as ferroptosis and adipocytokine signaling pathways. Eight core ferroptosis-related genes (ATF3, BNIP3, DDIT4, LPIN1, NOS2, NQO1, SLC2A1 and SLC2A6) were further selected in random forest model, which showed high diagnostic performance for PCOS. Seven of them were validated in GC samples, and five were found to be significantly and positively correlated with one or more oocyte quality parameters in PCOS patients, including oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and good-quality embryo rate. Gene regulatory network revealed JUN and HMGA1 as two important transcription factors, while dicoumarol and flavin adenine dinucleotide were predicted as small molecules with therapeutic potential. Conclusions: This is the first comprehensive report to study the differential expression of ferroptosis-related genes in GCs of PCOS and their clinical relevance with oocyte quality. Our findings could provide novel insights on the potential role of GC ferroptosis in PCOS pathogenesis, diagnosis, and targeted treatment.

Dynamics of Microbial Community Structure, Function and Assembly Mechanism with Increasing Stand Age of Slash Pine (Pinus elliottii) Plantations in Houtian Sandy Area, South China.

Establishing slash pine plantations is the primary method for restoring sandification land in the Houtian area of South China. However, the microbial variation pattern with increasing stand age remains unclear. In this study, we investigated microbial community structure and function in bare sandy land and four stand age gradients, exploring ecological processes that determine their assembly. We did not observe a significant increase in the absolute abundance of bacteria or fungi with stand age. Bacterial communities were dominated by Chloroflexi, Actinobacteria, Proteobacteria, and Acidobacteria; the relative abundance of Chloroflexi significantly declined while Proteobacteria and Acidobacteria significantly increased with stand age. Fungal communities showed succession at the genus level, with Pisolithus most abundant in soils of younger stands (1- and 6-year-old). Turnover of fungal communities was primarily driven by stochastic processes; both deterministic and stochastic processes influenced the assembly of bacterial communities, with the relative importance of stochastic processes gradually increasing with stand age. Bacterial and fungal communities showed the strongest correlation with the diameter at breast height, followed by soil available phosphorus and water content. Notably, there was a significant increase in the relative abundance of functional groups involved in nitrogen fixation and uptake as stand age increased. Overall, this study highlights the important effects of slash pine stand age on microbial communities in sandy lands and suggests attention to the nitrogen and phosphorus requirements of slash pine plantations in the later stages of sandy management.

A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Comparison of ventilation techniques for compensation of mask leakage using a ventilator and a regular full-face mask: A bench study.

Background: The use of noninvasive ventilation (NIV) during and after extubation is common. We designed this study to determine the optimal strategy to compensate for mask leaks and achieve effective ventilation during NIV by comparing commonly used operating room ventilator systems and a regular facemask. Methods: We tested four operating room ventilator systems (Dägger Zeus, Dägger Apollo, Dägger Fabius Tiro, and General Electric Healthcare Carestation 650) on a lung model with normal compliance and airway resistance and evaluated pressure control ventilation (PCV), volume control ventilation (VCV), and AutoFlow mode (VAF). We set the O2 flow at 10 L/min and the maximal flow at 13, 16, or 26 L/min. We simulated five leak levels, from no leak to over 40 L/min (I to V levels), using customized T-pieces placed between the lung model and the breathing circuit. We recorded the expired tidal volume (Vte) from the lung model and peak inspiratory pressure via two flow/pressure sensors that were placed distally and proximally to the T-pieces. Results: 1. Comparison of four ventilators: with any given ventilation mode, an increase in leak level caused a decrease in Vte. With PCV, only Zeus produced Vte larger than 150 ml at leak level V. 2. Effect of ventilation mode on Vte: across all four ventilators, PCV resulted in a higher Vte than VCV and VAF (P < 0.01). PCV mode with all ventilators at leak level II provided Vte values that were equal to or greater than those obtained with no leak. 3. Effect of O2 flow on Vte Using PCV mode: only Carestation 650 Vte at leak level II during PCV were significantly greater with 16 L/min O2 flow compared with 10 L/min O2 flow (P < 0.01). 4. Actual leak: increasing the O2 flow from 10 L/min to the maximum O2 flow dramatically increased the real leak with all 4 ventilators at any fixed leak level (P < 0.01). 5. Preset PIP vs. actual PIP with PCV: at low preset PIP and leak levels such as leak II and III, the discrepancy between preset PIP and actual PIP was small. The disparity between the preset and actual PIP grew when the target PIP and the leak level were raised. Conclusion: For NIV using a mask, the ventilator is preferred whose Pressure generator is Turbine, the PCV mode is preferred in the ventilation mode and the oxygen flow is set to 10 L/min or maximum oxygen flow.

Dietary regulation of intestinal stem cells in health and disease.

Diet is a critical regulator for physiological metabolism and tissue homeostasis, with a close relation to health and disease. As an important organ for digestion and absorption, the intestine comes into direct contact with many dietary components. The rapid renewal of its mucosal epithelium depends on the continuous proliferation and differentiation of intestinal stem cells (ISCs). The function and metabolism of ISCs can be controlled by a variety of dietary patterns including calorie restriction, fasting, high-fat, ketogenic, and high-sugar diets, as well as different nutrients including vitamins, amino acids, dietary fibre, and probiotics. Therefore, dietary interventions targeting ISCs may make it possible to prevent and treat intestinal disorders such as colon cancer, inflammatory bowel disease, and radiation enteritis. This review summarised recent research on the role and mechanism of diet in regulating ISCs, and discussed the potential of dietary modulation for intestinal diseases.

Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis.

Breast cancer (BC) is the most commonly diagnosed cancer worldwide. Advanced BC with brain metastasis (BM) is a major cause of mortality with no specific or effective treatment. Therefore, better knowledge of the cellular and molecular mechanisms underlying breast cancer brain metastasis (BCBM) is crucial for developing novel therapeutic strategies and improving clinical outcomes. In this review, we focused on the latest advances and discuss the contribution of the molecular subtype of BC, the brain microenvironment, exosomes, miRNAs/lncRNAs, and genetic background in BCBM. The blood-brain barrier and blood-tumor barrier create challenges to brain drug delivery, and we specifically review novel approaches to bypass these barriers. Furthermore, we discuss the potential application of immunotherapies and genetic editing techniques based on CRISPR/Cas9 technology in treating BCBM. Emerging techniques and research findings continuously shape our views of BCBM and contribute to improvements in precision therapies and clinical outcomes.

Quantitative determination of d-psicose based on flexible copper film materials and electrochemical scanning methods.

In this paper, a three-electrode electrochemical detection system was designed. Platinum electrode was used as the counter electrode, saturated KCl electrode as reference electrode, and copper film material as working electrode, respectively. Cyclic voltammetry (CV) and chronoamperometry (i-t) methods were used for d-psicose scanning. CV results indicated that d-psicose presented the oxidation-reduction reacting procedure on the surface of copper film electrode. Testing parameters optimization was conducted using CV scanning in different scanning rates. d-psicose quantitative determination model was developed by i-t scanning results. The sensitivity was9419.1A×cm-2·mol/L, the detection limit was1.04311×10-8mol/L. The proposed method has some advantages including high sensitivity, low detection line, and fast response speed. Negative control testing results by using glucose, sucrose, and NaCl solutions demonstrated that the proposed method had good selectivity.

Association of Long-term Oncologic Prognosis With Minimal Access Breast Surgery vs Conventional Breast Surgery.

Importance: Minimal access breast surgery (MABS) has been used in breast cancer management. However, long-term prognostic data associated with MABS vs conventional breast surgery (CBS) are lacking. Objective: To investigate long-term therapeutic outcomes associated with MABS vs CBS for breast cancer management. Design, Setting, and Participants: In this single-center retrospective cohort study, 9184 individuals were assessed for inclusion. After exclusions, 2412 adult female individuals were included who were diagnosed with stage 0 to III breast cancer, underwent unilateral breast surgery between January 2004 and December 2017, and had no distant metastasis or history of severe underlying disease. Propensity score matching was performed to minimize selection bias. Data were analyzed from January 1, 2004, to December 31, 2019. Exposures: MABS or CBS. Main Outcomes and Measures: Data on demographic and tumor characteristics and long-term outcomes were collected and analyzed. Results: This study included 2412 patients (100% female; median [IQR] age, 44 [40-49] years). Of these, 603 patients underwent MABS (endoscopic, endoscopy-assisted, or robot-assisted procedures in 289, 302, and 12 patients, respectively) and 1809 patients underwent CBS. The median follow-up time was 84 months (93 in the MABS group and 80 months in the CBS group). Intergroup differences were not significant for the following parameters: 10-year local recurrence-free survival (93.3% vs 96.3%; hazard ratio [HR], 1.39; 95% CI, 0.86-2.27; P = .18), regional recurrence-free survival (95.5% vs 96.7%; HR, 1.38; 95% CI, 0.81-2.36; P = .23), and distant metastasis-free survival (81.0% vs 82.0%; HR, 0.95; 95% CI, 0.74-1.23; P = .72). The 5-, 10-, and 15-year disease-free survival rates in the MABS group were 85.9%, 72.6%, and 69.1%, respectively. The corresponding rates in the CBS group were 85.0%, 76.6%, and 70.7%. The intergroup differences were not significant (HR, 1.07; 95% CI, 0.86-1.31; P = .55). The 5-, 10-, and 15-year overall survival rates in the MABS group were 92.0%, 83.7%, and 83.0%, respectively. The corresponding rates in the CBS group were 93.6%, 88.7%, and 81.0%. The intergroup differences were not significant (HR, 1.29; 95% CI, 0.97-1.72; P = .09). Post hoc subgroup analysis showed no significant intergroup differences in disease-free survival. Conclusions and Relevance: In this cohort study, long-term outcomes following MABS were not significantly different from those following CBS in patients with early-stage breast cancer. MABS may be a safe and feasible alternative in this patient population.

A novel pyroptosis-related indicator of immune infiltration features and prognosis in breast cancer.

Breast cancer is the most common malignancy in women, and there is evidence for the dual role of cell pyroptosis in tumor development. However, little is known about the relationship between cell pyroptosis and breast cancer and its prognostic value. We aimed to construct a prognostic model using cell-pyroptosis-related genes to provide innovative insights into the prognosis and treatment of breast cancer. We screened candidate genes for pyroptosis using public databases and identified 10 cell pyroptosis signature genes with the random forest method. Finally, a nomogram for predicting 1-, 3-, and 5-year survival probabilities was constructed. The differences in immune cell distributions between survival periods were similar across the breast cancer datasets. The 10 identified key pyroptosis factors showed a significant correlation with Her2, tumor-node-metastasis (TNM) stage, and survival of breast cancer. The risk scores correlated positively with the infiltration features of naive B cells, CD8+ T cells, atpdelnd mast cells, while they correlated negatively with those of M0 macrophages and dendritic cells. In conclusion, our findings confirm that cell pyroptosis is closely associated with breast cancer. Importantly, the prognostic complex values generated from the 10 cell-pyroptosis-related genes based on various clinical features may provide an important basis for future studies on the prognosis of breast cancer.

Dynamic and epistatic QTL mapping reveals the complex genetic architecture of waterlogging tolerance in chrysanthemum.

MAIN CONCLUSION: 37 unconditional QTLs, 51 conditional QTLs and considerable epistatic QTLs were detected for waterlogging tolerance, and six favourable combinations were selected accelerating the possible application of MAS in chrysanthemum breeding. Chrysanthemum is seriously impacted by soil waterlogging. To determine the genetic characteristics of waterlogging tolerance (WAT) in chrysanthemum, a population of 162 F1 lines was used to construct a genetic map to identify the dynamic and epistatic quantitative trait loci (QTLs) for four WAT traits: wilting index (WI), dead leaf ratio (DLR), chlorosis score (Score) and membership function value of waterlogging (MFVW). The h B2 for the WAT traits ranged from 0.49 to 0.64, and transgressive segregation was observed in both directions. A total of 37 unconditional consensus QTLs with 5.81-18.21% phenotypic variation explanation (PVE) and 51 conditional consensus QTLs with 5.90-24.56% PVE were detected. Interestingly, three unconditional consensus QTLs were consistently identified across different stages, whereas no conditional consensus QTLs were consistently expressed. In addition, considerable epistatic QTLs, all with PVE values ranging from 0.01 to 8.87%, were detected by a joint analysis of WAT phenotypes. These results illustrated that the QTLs (genes) controlling WAT were environmentally dependent and selectively expressed at different times and indicated that both additive and epistatic effects underlie the inheritance of WAT in chrysanthemum. The findings of the current study provide insights into the complex genetic architecture of WAT, and the identification of favourable alleles represents an important step towards the application of molecular marker-assisted selection (MAS) and QTL pyramiding in chrysanthemum WAT breeding programmes.