[Effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery for early-stage breast cancer in different quadrants].

Objective: To compare the effectiveness of sequential method pure single-port lumpectomy-breast conserving surgery (SMPSL-BCS) in treating early-stage breast cancer patients with tumors in different quadrants. Methods: A retrospective analysis was conducted on 200 early-stage breast cancer female patients admitted between January 2023 and December 2023. According to the quadrant where the tumor was located, the patients were allocated into the upper outer quadrant group (UO group), lower outer quadrant group (LO group), upper inner quadrant group (UI group), and lower inner quadrant group (LI group), with 50 cases in each group. There was no significant difference ( P>0.05) in the baseline data, including age, body mass index, smoking history, marital status, comorbidities, affected breast side, maximum tumor diameter on ultrasound, maximum pathological tumor diameter, clinical tumor stage, molecular subtype, and disease duration. The operation time, intraoperative blood loss, postoperative drainage volume, and extubation time were recorded and compared between groups. Additionally, the occurrence of early-stage complications (1-3 months after operation; including subcutaneous fluid accumulation, incision infection, superficial skin burns) and late-stage complications (>3 months after operation; including pectoralis major muscle adhesion, changes in breast appearance and shape, sensory discomfort) were assessed. At 6 months after operation, the cosmetic outcome of breast-conserving surgery was rated for all groups. Results: The UO group had the shortest operation time, followed by the UI group, LO group, and LI group, showing significant differences between groups ( P<0.05). The UO group had the least intraoperative blood loss, followed by the LO group, UI group, and LI group; except for the difference between UO group and LO group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The UO group had the least postoperative drainage volume, followed by the LO group, UI group, and LI group; except for the difference between LO group and UI group, which was not significant ( P>0.05), the differences between the other groups were significant ( P<0.05). The extubation time of the LI group was significantly longer than that of the other groups ( P<0.05). All patients were followed up 4-12 months, with an average of 8 months. And 193 patients were followed up more than 6 months, including 48 patients in UO group, 47 in LO group, 49 in UI group, and 49 in LI group. In the early-stage period, the LI group had a higher incidence of subcutaneous fluid accumulation after tube removal compared to the UO group and LO group ( P<0.05), while there was no significant difference in the incidences of other early complications between groups ( P>0.05). In the late-stage period, the LI group had significantly higher incidences of pectoralis major muscle adhesion and changes in breast appearance and shape than UO group and LO group ( P<0.05), and a significantly higher incidence of sensory discomfort than UO group ( P<0.05). There was no significant difference in the incidences of other late-stage complications between groups ( P>0.05). At 6 months after operation, the cosmetic outcomes of breast-conserving surgery were significantly better in UO group, LO group, and UI group than in LI group ( P<0.05); there was no significant difference between the other groups ( P>0.05). Conclusion: In the treatment of early-stage breast cancer using SMPSL-BCS, patients with tumors located in the upper outer quadrant show the best effectiveness. The effectivenesses are similar for patients with tumors in the lower outer and upper inner quadrants. However, patients with tumors in the lower inner quadrant do not experience significant advantages. Therefore, it is recommended that SMPSL-BCS should not be the first-choice surgical method for patients with tumors in the lower inner quadrant.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Analysis of Fungal Diversity, Physicochemical Properties and Volatile Organic Compounds of Strong-Flavor Daqu from Seven Different Areas.

Strong-flavor Daqu, as a fermentation agent, plays a significant role in shaping the quality of strong-flavor baijius, and fungal species in Daqu are important factors affecting the quality of Daqu. Therefore, we selected strong-flavor Daqu from seven different origins to study the fungal composition and the effects of the fungal composition on the physicochemical properties and volatile organic compounds (VOCs). It was found that the fungal composition influences the physicochemical properties of Daqu. Specifically, there was a positive link between Rhizomucor, Rhizopus, Thermomyces, and liquefying activity and a positive correlation between Aspergillus and fermenting activity. Furthermore, the relationships between esterifying activity and Thermomyces, Rhizomucor, Aspergillus, Pichia, and Saccharomycopsis were found to be positive. The VOCs in Daqu were affected by Aspergillus, Issatchenkia, Pichia, and Thermoascus. Issatchenkia was significantly positively correlated with benzeneethanol as well as Aspergillus and pentadecanoic acid ethyl ester, ethyl myristate. Pichia and Thermoascus were significantly negatively correlated with benzaldehyde and 2-furaldehyde. This study deepens our understanding of the relationship between VOCs, the physicochemical properties with microbial communities, and reference significance for the production of better-quality strong-flavor Daqu.

Lactiplantibacillus plantarum A72, a Strain with Antioxidant Properties, Obtained through ARTP Mutagenesis, Affects Caenorhabditis elegans Anti-Aging.

This research endeavored to elucidate the antioxidant attributes of lactic acid bacteria, specifically their impact on anti-aging and lifespan augmentation in Caenorhabditis elegans. The study focused on Lactiplantibacillus plantarum A72, identified through ARTP mutagenesis for its potent antioxidant properties. In vitro analysis affirmed its free radical neutralizing capacity. In C. elegans, the strain not only extended the lifespan by 25.13% and amplified motility 2.52-fold, but also maintained reproductive capabilities. Remarkably, Lpb. plantarum A72 diminished reactive oxygen species (ROS) and malondialdehyde (MDA) levels in C. elegans by 34.86% and 69.52%, respectively, while concurrently enhancing its antioxidant enzyme activities. The strain also bolstered C. elegans survival rates by 46.33% and 57.78% under high temperature and H2O2 conditions, respectively. Transcriptomic scrutiny revealed that Lpb. plantarum A72 could retard C. elegans aging and extend lifespan by upregulating the sod-5 and hsp-16.1 genes and downregulating the fat-6 and lips-17 genes. These findings propose Lpb. plantarum A72 as a potential antioxidant and anti-aging lactic acid bacteria.

Mechanism of scutellarin inhibition of astrocyte activation to type A1 after ischemic stroke.

OBJECTIVE: The aim of this study was to investigate the effects of scutellarin on the activation of astrocytes into the A1 type following cerebral ischemia and to explore the underlying mechanism. METHODS: In vivo, a mouse middle cerebral artery wire embolism model was established to observe the regulation of astrocyte activation to A1 type by scutellarin, and the effects on neurological function and brain infarct volume. In vitro, primary astrocytes were cultured to establish an oxygen-glucose deprivation model, and the mRNA and protein expression of C3, a specific marker of A1-type astrocytes pretreated with scutellarin, were examined. The neurons were cultured in vitro to detect the toxic effects of ischemia-hypoxia-activated A1 astrocyte secretion products on neurons, and to observe whether scutellarin could reduce the neurotoxicity of A1 astrocytes. To validate the signaling pathway-related proteins regulated by scutellarin on C3 expression in astrocytes. RESULTS: The results showed that scutellarin treatment reduced the volume of cerebral infarcts and attenuated neurological deficits in mice caused by middle cerebral artery embolism. Immunofluorescence and Western blot showed that treatment with scutellarin down-regulated middle cerebral artery embolism and OGD/R up-regulated A1-type astrocyte marker C3. The secretory products of ischemia-hypoxia-activated A1-type astrocytes were toxic to neurons and induced an increase in neuronal apoptosis, and astrocytes treated with scutellarin reduced the toxic effects on neurons. Further study revealed that scutellarin inhibited the activation of NF-κB signaling pathway and thus inhibited the activation of astrocytes to A1 type.

Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes.

PURPOSE: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)-positive breast cancer patients under different genotypes. MATERIALS AND METHODS: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. RESULTS: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). CONCLUSION: Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

CX3CR1 mediates motor dysfunction in mice through 5-HTR2a.

CX3CR1 knockout could induce motor dysfunction in several neurological disease models mainly through regulating microglia's function. While CX3CR1 was expressed on neurons in a few reports, whether neuronal CX3CR1 could affect the function of neurons and mediate motor dysfunction under physiological conditions is unknown. To elucidate the roles of neuronal CX3CR1 on motor dysfunction, CX3CR1 knockout mice were created. Rotarod test and Open field test found that the CX3CR1-/- mice's motor capacity was reduced. Immunofluorescence staining detected the expression of CX3CR1 in neurons both in vivo and in vitro. Immunohistochemistry and West blot found that knockout of CX3CR1 did not affect the neurons' number in both spinal cord and brain of mice. While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function. Further investigation revealed that CX3CR1 regulated the expression of HTR2a through the NF-κB pathway. For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction.

Chemical Composition and Flavor Characteristics of Cider Fermented with Saccharomyces cerevisiae and Non-Saccharomyces cerevisiae.

Cider flavor has a very important impact on the quality. Solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) combined with gas chromatography-ion mobility spectrometry (GC-IMS) tested different kinds of non-Saccharomyces yeasts and Saccharomyces cerevisiae (S. cerevisiae) co-inoculated for the fermentation of cider to determine differences in aroma material, and the determination of odor activity value (OAV) is applied less frequently in research. Through Rhodotorula mucilaginosa, Debaryomyces hansenii, Zygosaccharomyces bailii, and Kluyveromyces Marxianus, four different strains of non-Saccharomyces yeast fermented cider, and it was found that, in both the chemical composition and flavor of material things, compared with monoculture-fermented cider using S. cerevisiae, all differences were significant. Co-inoculated fermentation significantly improved the flavor and taste of cider. As in the volatile compounds of OVA > 1, octanoic acid (Sc 633.88 µg/L, co-inoculation fermented group 955.49 µg/L) provides vegetable cheese fragrance and decanoic acid, ethyl ester (Sc 683.19 µg/L, co-inoculation fermented group 694.98 µg/L) a creamy fruity fragrance, etc., and the average content increased after co-inoculated fermentation. Phenylethyl alcohol, which can produce a rose scent, was relatively abundant in cider samples and varied greatly among the groups. Moreover, the contents of ethyl lactate and 1-butanol in the Sc+Rm (ciders fermented by S. cerevisiae and R. mucilaginosa) were the highest of all of the cider samples. Different types of non-Saccharomyces yeast produced cider with different flavor characteristics. This study demonstrates that different species of non-Saccharomyces yeast do have an important impact on the characteristics of cider and that co-inoculation with non-Saccharomyces yeast and S. cerevisiae for cider fermentation may be a strategy to improve the flavor of cider.

Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio.

Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10-15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients.

Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment.

Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanisms underlying its promotion by breast cancer stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME to facilitate LNM. Utilizing single-cell RNA sequencing, we profiled TIME in primary cancer and corresponding metastatic lymph node samples from patients at our institution. To verify the derived data, we cultured CSCs and performed validation assays employing flow cytometry and CyTOF. Our analysis revealed distinct differences in cellular infiltration patterns between tumor and LNM samples. Importantly, RAC2 and PTTG1 double-positive CSCs, which exhibit the highest stem-like attributes, were markedly enriched in metastatic lymph nodes. These CSCs are hypothesized to foster metastasis via activation of specific metastasis-related transcription factors and signaling pathways. Additionally, our data suggest that CSCs might modulate adaptive and innate immune cell evolution, thereby further contributing to metastasis. In summary, this study illuminates a critical role of CSCs in modifying TIME to facilitate LNM. The enrichment of highly stem-like CSCs in metastatic lymph nodes offers novel therapeutic targeting opportunities and deepens our understanding of breast cancer metastasis.

FN1 mediated activation of aspartate metabolism promotes the progression of triple-negative and luminal a breast cancer.

BACKGROUND: Breast cancer (BC) is regarded as one of the most common cancers diagnosed among the female population and has an extremely high mortality rate. It is known that Fibronectin 1 (FN1) drives the occurrence and development of a variety of cancers through metabolic reprogramming. Aspartic acid is considered to be an important substrate for nucleotide synthesis. However, the regulatory mechanism between FN1 and aspartate metabolism is currently unclear. METHODS: We used RNA sequencing (RNA seq) and liquid chromatography-mass spectrometry to analyze the tumor tissues and paracancerous tissues of patients. MCF7 and MDA-MB-231 cells were used to explore the effects of FN1-regulated aspartic acid metabolism on cell survival, invasion, migration and tumor growth. We used PCR, Western blot, immunocytochemistry and immunofluorescence techniques to study it. RESULTS: We found that FN1 was highly expressed in tumor tissues, especially in Lumina A and TNBC subtypes, and was associated with poor prognosis. In vivo and in vitro experiments showed that silencing FN1 inhibits the activation of the YAP1/Hippo pathway by enhancing YAP1 phosphorylation, down-regulates SLC1A3-mediated aspartate uptake and utilization by tumor cells, inhibits BC cell proliferation, invasion and migration, and promotes apoptosis. In addition, inhibition of FN1 combined with the YAP1 inhibitor or SLC1A3 inhibitor can effectively inhibit tumor growth, of which inhibition of FN1 combined with the YAP1 inhibitor is more effective. CONCLUSION: Targeting the "FN1/YAP1/SLC1A3/Aspartate metabolism" regulatory axis provides a new target for BC diagnosis and treatment. This study also revealed that intratumoral metabolic heterogeneity plays an important role in the progression of different subtypes of breast cancer.

Association of NCAP family genes with prognosis and immune infiltration of human sarcoma.

OBJECTIVE: This study was conducted to explore the correlation of NCAP family genes with expression, prognosis, and immune infiltration in human sarcoma. RESULTS: Compared with normal human tissues, six NCAP family genes were highly expressed in sarcoma tissues, and high expression of the six genes were significantly associated with the poor prognosis of sarcoma patients. The expression of NCAPs in sarcoma was significantly related to the low infiltration level of macrophages and CD4+ T cells. GO and KEGG enrichment analysis showed that NCAPs and their interacting genes were mainly enriched in organelle fission for biological processes (BP), spindle for cellular component (CC), tubulin binding for molecular function (MF), and 'Cell cycle' pathway. METHODS: We explored the expression of NCAP family members by ONCOMINE, and GEPIA databases. Additionally, the prognostic value of NCAP family genes in sarcoma was detected by Kaplan-Meier Plotter and GEPIA databases. Moreover, we explored the relationship between NCAP family gene expression level and immune infiltration using the TIMER database. Finally, we performed GO and KEGG analysis for NCAPs-related genes by DAVID database. CONCLUSION: The six members of NCAP gene family can be used as biomarkers to predict the prognosis of sarcoma. They were also correlated with the low immune infiltration in sarcoma.

Narrower-band multiplet resonances of surface plasmons on periodically phase-shifted metal gratings.

In this Letter, we report properties of surface plasmon resonances (SPRs) on metal gratings with periodic phase shifts, in which high-order SPR modes corresponding to the long-pitch (a few to tens of wavelengths, λ) phase shifts are excited, instead of those corresponding to the short-pitch (∼λ) gratings. In particular, it is shown that, for quarter-phase shifts, spectral features of doublet SPR modes with narrower bandwidths are notably present when the underlying first-order short-pitch SPR mode is designed to be located between an arbitrarily chosen pair of neighboring high-order long-pitch SPR modes. Also, the positions and interspacing of the doublet SPR modes can be arbitrarily tuned by adjusting the pitch values. Resonance characteristics of this phenomenon are numerically investigated, and an analytical formulation based on coupled-wave theory is developed to elucidate the resonance conditions. Characteristics of the narrower-band doublet SPR modes may find application in the resonant control of light-matter interactions involving photons of multiple frequencies, and in high-precision SPR sensing with multi-probing channels.

Risk factors for target vessel endoleaks after physician-modified fenestrated or branched endovascular aortic repair for postdissection thoracoabdominal aortic aneurysms.

OBJECTIVE: Patients with postdissection thoracoabdominal aortic aneurysms (TAAAs) have been more likely to develop endoleaks than those with degenerative TAAAs after fenestrated or branched endovascular aortic repair (F/BEVAR). In the present study, we aimed to determine the risk factors for target vessel (TV)-related endoleaks after visceral segment F/BEVAR for postdissection TAAAs. METHODS: We performed a retrospective analysis of all patients with degenerative and postdissection TAAAs treated with F/BEVAR between 2017 and 2021. All the patients had undergone computed tomography angiography before and 3 months, 6 months, and annually after discharge. Two experienced vascular surgeons had used data from computed tomography angiography and vascular angiography to judge the presence of endoleaks. The study end points were mortality, aneurysm rupture, and the emergence of and reintervention for TV-related endoleaks. RESULTS: A total of 195 patients (mean age, 66 ± 10 years; 69% men) had undergone F/BEVAR for 99 postdissection TAAAs and 96 degenerative TAAAs. During a mean follow-up of 16 ± 12 months, we found that the patients with postdissection TAAAs were younger (age, 64 ± 10 years vs 69 ± 9 years; P = .001), had required more prior aortic repairs (58% vs 40%; P = .012), and had had a higher body mass index (26.1 ± 3.4 kg/m2 vs 24.8 ± 3 kg/m2; P = .008), a larger visceral segment aortic diameter (47.1 ± 7.5 mm vs 44.5 ± 7.5 mm; P = .016), and more TV-related endoleaks (18% vs 7%; P = .023) compared with those with degenerative TAAAs. Of the 99 patients with postdissection TAAAs, 327 renal-mesenteric arteries were revascularized using 12 scallops, 141 fenestrations, and 174 inner or outer branch stents. A total of 25 TV-related endoleaks were identified among 18 patients during follow-up, including 6 type Ic (retrograde from the distal end of the branch), 3 type IIIb (bridging stent fabric tear), and 16 type IIIc endoleaks (detachment or loose connection of the bridging stent). The patients with an endoleak had had a larger visceral aortic diameter (52.7 ± 6.4 mm vs 45.8 ± 7.2 mm; P < .001) and had undergone revascularization of more TVs (3.7 ± 0.7 vs 3.2 ± 0.9; P = .032). In contrast, true lumen compression did not seem to affect the occurrence of TV endoleaks (39% vs 27%; P = .323). The use of presewn branch stents in the fenestration position was associated with a lower risk of TV-related endoleaks (5% vs 11%; P = .025). In addition, TVs derived entirely or partially from the false lumen were more prone to the development of endoleaks after reconstruction (19% vs 4% [P < .001]; and 15% vs 4% [P = .047], respectively). CONCLUSIONS: We found that patients with postdissection TAAAs were more likely to have TV-related endoleaks after F/BEVAR in the visceral region than those with degenerative TAAAs. Additionally, patients with a larger aortic diameter and a greater number of fenestrations in the visceral region were more likely to have experienced TV-related endoleaks. Branch vessels deriving from the false lumen were also more likely to develop endoleaks after reconstruction, and prefabricated branch stents were related to a lower possibility of TV-related endoleaks.

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.

Single cell profiling of primary and paired metastatic lymph node tumors in breast cancer patients.

The microenvironment of lymph node metastasized tumors (LNMT) determines tumor progression and response to therapy, but a systematic study of LNMT is lacking. Here, we generate single-cell maps of primary tumors (PTs) and paired LNMTs in 8 breast cancer patients. We demonstrate that the activation, cytotoxicity, and proliferation of T cells are suppressed in LNMT compared with PT. CD4+CXCL13+ T cells in LNMT are more likely to differentiate into an exhausted state. Interestingly, LAMP3+ dendritic cells in LNMT display lower T cell priming and activating ability than in PT. Additionally, we identify a subtype of PLA2G2A+ cancer-associated fibroblasts enriched in HER2+ breast cancer patients that promotes immune infiltration. We also show that the antigen-presentation pathway is downregulated in malignant cells of the metastatic lymph node. Altogether, we characterize the microenvironment of LNMT and PT, which may shed light on the individualized therapeutic strategies for breast cancer patients with lymph node metastasis.

Effect of Autochthonous Lactic Acid Bacteria-Enhanced Fermentation on the Quality of Suancai.

The lactic acid bacteria (LABs) used for fermentation have an extremely vital impact on the quality of Suancai, a fermented vegetable. The bacterial diversity and metabolites of inoculated Suancai with LABs, including Lactiplantibacillus plantarum (Lb. plantarum), Levilactabacillus brevis (Lb. brevis), and Leuconostoc mesenteroides (Leu. mesenteroides), were investigated. The inoculation of LABs significantly decreased the pH and the content of nitrite. The Suancai inoculated with LABs had a higher content of the total titratable acidity (TTA) and organic acids than spontaneous fermentation. The LABs inoculation significantly influenced the bacterial community structures, which directly or indirectly caused changes of metabolites. The bacterial community profiles of Suancai inoculated with Lb. plantarum were more similar to spontaneous fermentation. The inoculation of Lb. plantarum, Lb. brevis, and Leu. mesenteroides could increase its abundance in Suancai. Whatever the species inoculated, Lb. plantarum was always the predominant bacterium in Suancai after fermentation. The inoculated LABs were positively correlated with most volatile compounds and amino acids. The inoculated LABs significantly improved the volatile compounds and amino acid content of Suancai. This study could contribute to understanding the function of starters in Suancai fermentation and promote the selection of applicable starters for high-quality Suancai production.

Combining Immune-Related Genes For Delineating the Extracellular Matrix and Predicting Hormone Therapy and Neoadjuvant Chemotherapy Benefits In Breast Cancer.

Breast cancer (BC) is the most prevalent cancer in women worldwide. A systematic approach to BC treatment, comprising adjuvant and neoadjuvant chemotherapy (NAC), as well as hormone therapy, forms the foundation of the disease's therapeutic strategy. The extracellular matrix (ECM) is a dynamic network that exerts a robust biological effect on the tumor microenvironment (TME), and it is highly regulated by several immunological components, such as chemokines and cytokines. It has been established that the ECM promotes the development of an immunosuppressive TME. Therefore, while analyzing the ECM of BC, immune-related genes must be considered. In this study, we used bioinformatic approaches to identify the most valuable ECM-related immune genes. We used weighted gene co-expression network analysis to identify the immune-related genes that potentially regulate the ECM and then combined them with the original ECM-related gene set for further analysis. Least absolute shrinkage and selection operator (LASSO) regression and SurvivalRandomForest were used to narrow our ECM-related gene list and establish an ECM index (ECMI) to better delineate the ECM signature. We stratified BC patients into ECMI high and low groups and evaluated their clinical, biological, and genomic characteristics. We found that the ECMI is highly correlated with long-term BC survival. In terms of the biological process, this index is positively associated with the cell cycle, DNA damage repair, and homologous recombination but negatively with processes involved in angiogenesis and epithelial-mesenchymal transition. Furthermore, the tumor mutational burden, copy number variation, and DNA methylation levels were found to be related to the ECMI. In the Metabric cohort, we demonstrated that hormone therapy is more effective in patients with a low ECMI. Additionally, differentially expressed genes from the ECM-related gene list were extracted from patients with a pathologic complete response (pCR) to NAC and with residual disease (RD) to construct a neural network model for predicting the chance of achieving pCR individually. Finally, we performed qRT-PCR to validate our findings and demonstrate the important role of the gene OGN in predicting the pCR rate. In conclusion, delineation of the ECM signature with immune-related genes is anticipated to aid in the prediction of the prognosis of patients with BC and the benefits of hormone therapy and NAC in BC patients.