Atrimonas thermophila gen. nov., sp. nov., a novel anaerobic thermophilic bacterium of the phylum Atribacterota isolated from deep subsurface gas field and proposal of Atrimonadaceae fam. nov. within the class Atribacteria in the phylum Atribacterota.

A novel anaerobic, thermophilic bacterium of the class Atribacteria, strain M15T, was isolated from a high-temperature gas reservoir, Japan. Cells of strain M15T were gram-negative, short oval-shaped, and lacked flagella. Growth occurred at 45-75 °C (optimum 70-75 °C) and pH 6.5-8.5 (optimum pH 7.5-8.0) and was fast under optimal conditions (doubling time 11.4 h). Yeast extract was required for growth. Fermentative growth with glucose, arabinose, xylose, and cellobiose was observed. The major fermentative end products of glucose were acetate and hydrogen. The major cellular fatty acids were C16:0, iso-C15:0, and C18:0. The genomic G + C content was 46.0 mol%. Fluorescence and electron microscopy observations revealed the intracellular localization of genomic DNA surrounded by a membrane in the cells of strain M15T as reported in a sole validly described species of the class Atribacteria in the phylum Atribacterota, Atribacter laminatus strain RT761T, suggesting that the unique morphological traits are widely shared in this class. Phylogenetic analyses indicated that strain M15T belongs to a distinct family-level lineage in the class Atribacteria and shows low similarities to Atribacter laminatus strain RT761T (16S rRNA gene sequence identity of 90.1 %, average nucleotide identity [ANI] of 66.1 %, average amino acid identity [AAI] of 55.8 %). Phenotypic traits of strain M15T (thermophilic, fast-growing, relatively high G + C content, etc.) were clearly distinct from A. laminatus. Based on these phenotypic and genomic properties, we propose a novel genus and species, Atrimonas thermophila gen. nov., sp. nov. for strain M15T (=JCM39389T, =KCTC25731T) representing a novel family Atrimonadaceae fam., nov. in the class Atribacteria.

Research progress in stem cell therapy for Wilson disease.

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive disorder characterized by disorganized copper metabolism caused by mutations in the ATP7B gene. Currently, the main treatment options for WD involve medications such as d-penicillamine, trientine hydrochloride, zinc acetate, and liver transplantation. However, there are challenges that encompass issues of poor compliance, adverse effects, and limited availability of liver sources that persist. Stem cell therapy for WD is currently a promising area of research. Due to the advancement in stem cell directed differentiation technology in vitro and the availability of sufficient stem cell donors, it is expected to be a potential treatment option for the permanent correction of abnormal copper metabolism. This article discusses the research progress of stem cell therapy for WD from various sources, as well as the challenges and future prospects of the clinical application of stem cell therapy for WD.

Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats.

OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

Loss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex.

For a long time, myelin was thought to be restricted to excitatory neurons, and studies on dysmyelination focused primarily on excitatory cells. Recent evidence showed that axons of inhibitory neurons in the neocortex are also myelinated, but the role of myelin on inhibitory circuits remains unknown. Here we studied the impact of mild hypomyelination on both excitatory and inhibitory connectivity in the primary auditory cortex (A1) with well-characterized mouse models of hypomyelination due to loss of oligodendrocyte ErbB receptor signaling. Using laser-scanning photostimulation, we found that mice with mild hypomyelination have reduced functional inhibitory connections to A1 L2/3 neurons without changes in excitatory connections, resulting in altered excitatory/inhibitory balance. These effects are not associated with altered expression of GABAergic and glutamatergic synaptic components, but with reduced density of parvalbumin-positive (PV+ ) neurons, axons, and synaptic terminals, which reflect reduced PV expression by interneurons rather than PV+ neuronal loss. While immunostaining shows that hypomyelination occurs in both PV+ and PV- axons, there is a strong correlation between MBP and PV expression, suggesting that myelination influences PV expression. Together, the results indicate that mild hypomyelination impacts A1 neuronal networks, reducing inhibitory activity, and shifting networks towards excitation.

Echinacoside exerts its protective effects in a type 2 diabetes mellitus injury model via the AKT pathway.

Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.

Microstructure Evolution and Its Correlation with Performance in Nitrogen-Containing Porous Carbon Prepared by Polypyrrole Carbonization: Insights from Hybrid Calculations.

The preparation of nitrogen-containing porous carbon (NCPC) materials by controlled carbonization is an exciting topic due to their high surface area and good conductivity for use in the fields of electrochemical energy storage and conversion. However, the poor controllability of amorphous porous carbon prepared by carbonization has always been a tough problem due to the unclear carbonation mechanism, which thus makes it hard to reveal the microstructure-performance relationship. To address this, here, we comprehensively employed reactive molecular dynamics (ReaxFF-MD) simulations and first-principles calculations, together with machine learning technologies, to clarify the carbonation process of polypyrrole, including the deprotonation and formation of pore structures with temperature, as well as the relationship between microstructure, conductance, and pore size. This work constructed ring expressions for PPy thermal conversion at the atomic level. It revealed the structural factors that determine the conductivity and pore size of carbonized products. More significantly, physically interpretable machine learning models were determined to quantitatively express structure factors and performance structure-activity relationships. Our study also confirmed that deprotonation preferentially occurred by desorbing the dihydrogen atom on nitrogen atoms during the carbonization of PPy. This theoretical work clearly reproduces the microstructure evolution of polypyrrole on an atomic scale that is hard to do via experimentation, thus paving a new way to the design and development of nitrogen-containing porous carbon materials with controllable morphology and performance.

Ototoxicity in patients with invasive ductal breast cancer who were treated with docetaxel: report of two cases.

Docetaxel is an important anti-microtubule agent used to treat a variety of solid tumors, including breast cancer; notably, docetaxel-containing regimens improve outcomes for patients in metastatic, adjuvant, and neoadjuvant settings. However, the effectiveness of docetaxel in clinical practice can be compromised by suboptimal management of side effects. Here, we report two cases of docetaxel-based chemotherapy regimens in patients who exhibited invasive ductal breast cancer and underwent two different clinical treatment approaches. A 58-year-old postmenopausal female received salvage treatment with 8 cycles of docetaxel (67 mg/m2), and a 74-year-old female received 1 cycle of docetaxel (100 mg/m2). The two patients exhibited considerable hearing loss two days later. Of note, both patients had no hearing loss symptoms prior to docetaxel. Thus, ototoxicity may be a side effect of docetaxel that should be considered during treatment.

Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRPα axis blockade, induces modest phagocytic activity and a low response rate for monotherapy, resulting in failures in clinical trials. We showed that BP-mediated ablation of tumours through photothermal effects could serve as an effective strategy for specific immunological stimulation, improving the inherently poor immunogenicity of tumours, which is particularly useful for enhancing cancer immunotherapy. BP in combination with aCD47 blockade activates both innate and adaptive immunities and promotes local and systemic anticancer immune responses, thus offering a synergistically enhanced effect in suppression of tumour progression and in inducing abscopal effects for inhibition of metastatic cancers. Our combination strategy provides a promising platform in which photothermal agents could help to enhance the therapeutic efficacy of immunotherapy.

Is There a Role for Post-Mastectomy Radiotherapy for T1-2N1 Breast Cancers With Node-Positive Pathology After Patients Become Node-Negative Pathology Following Neoadjuvant Chemotherapy?

Purpose: To assess the benefit of post-mastectomy radiotherapy (PMRT) in breast cancer (BC) patients with T1-2N1M0 who developed pathologically negative lymph nodes (ypN0) after undergoing neoadjuvant chemotherapy (NAC) and mastectomy. Patients and Materials: Patients with T1-2 tumors and positive lymph node(s) who became pN0 after NAC and mastectomy were screened from our prospectively maintained database. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints were local recurrence-free survival (LRFS) and overall survival (OS). Propensity-score matching (PSM) was conducted for the comparison between PMRT and non-PMRT groups. Results: Of the 142 eligible patients, 110 (77.5%) received PMRT, and 32 (22.5%) did not. The median follow-up time was 72 months. Univariate analyses showed that the 5-year RFS, LRFS, and OS rates were 88.7, 94.5, and 96.1, respectively, with PMRT and 72.4, 90.1, and 95.0% without PMRT (p = 0.028; p = 0.151; p = 0.971). Multivariate analyses established PMRT as a significant prognostic factor for RFS rate (HR, 0.411; 95% CI, 0.175-0.968; p = 0.042). After a PSM analysis (64 in the PMRT group vs. 32 in the non-PMRT group), PMRT remained significant, with improved RFS in univariate and multivariate analysis (with 5-year RFS rates of 90.1 vs. 72.4%, respectively, p = 0.016; HR, 0.323, 95%CI, 0.115-0.913, p = 0.033). In the subgroup of 48 (33.8%) patients with pathologic complete responses (pCR, ypT0, and ypN0) after NAC, PMRT did not affect RFS (HR, 0.226; 95% CI, 0.034-1.500; p = 0.123). Conclusions: PMRT might benefit pT1-2N1M0 patients with pN0 after NAC. Patients with pCR might consider omitting PMRT. Prospective studies are needed to assess the effect of PMRT on this specific patient population.

Low-grade appendiceal mucinous neoplasms confined to the appendix: clinical manifestations and CT findings.

The clinical findings and CT images are investigated in order to fulfill an early preoperative diagnosis and increase awareness of low-grade appendiceal mucinous neoplasm (LAMN) confined to the appendix. 17 cases with histologically proven LAMNs confined to the appendix were included in this study. All patients had received multiphase CT examinations before the surgery. The imaging criteria included shape, size, margin, attenuation, secondary degeneration and internal mass enhancement pattern. In CT images, all cases appeared as oval or tubular cystic masses (average attenuation 20.4±3.6 Hounsfield units), with the longest dimensions ranging from approximately 38 to 106 mm (mean 66.3 mm), and the ratio of length against width was 1.83 in average. The cystic wall was unevenly thickened, with a mean maximal wall thickness of 5.7 mm (>10 mm in 3 cases). The inner capsule wall was rough, and calcification was observed in 3 cases. A few amounts of periappendiceal fat stranding were noted in 2 cases. Mild ring mural enhancement of the cystic wall was seen during the arterial phase, with progressive enhancement during the portal venous phase. In addition, mini enhancing mural nodules was observed in 5 cases. Although preoperative diagnosis of LAMNs confined to the appendix remains challenging, it should be considered when a focal well-defined cystic mass with slightly higher than water attenuation, thickened cystic wall with ring mural enhancement and a characteristic progressive contrast enhancement in CT imaging, especially in older females with non-specific symptoms similar to appendicitis.

An ICT-based fluorescence enhancement probe for detection of Sn2+ in cancer cells.

Development of a novel fluorescence enhancement probe for detection of Sn2+ in organisms, with high selectivity and sensitivity, is of great interest but remains a great challenge. Herein, an ICT-based fluorescence probe TPPB was rationally developed to act as an 'enhancement' luminescent and "naked-eye" indicator for Sn2+ detection. Importantly, spectroscopic studies indicated that TPPB was a fluorescence enhancement sensor for Sn2+ with rapid response, low detection limit (0.116 µM) and excellent binding constant (1.6 × 104 M-1). The mechanism of TPPB response to Sn2+ was further proved by 1H NMR titration, and enhancement calculations. Furthermore, TPPB is applied as a fluorescence probe for imaging in Hela cells, indicated that it can be potentially applied for Sn2+ sensing in biological fields.

Electrochemiluminescent immunoassay for the lung cancer biomarker CYFRA21-1 using MoOx quantum dots.

Molybdenum oxide quantum dots (MoOx QDs) were synthesized by a one-pot method and used as a versatile probe in an electrochemiluminescent (ECL) immunoassay of the non-small cell lung cancer biomarker cytokeratin 19 fragment 21-1 (CYFRA21-1) as a model analyte. The MoOx QDs exhibited stable and strong cathodic green ECL, with an emission peak at 535 nm, in the presence of K2S2O8 within the potential range of -2.0 to 0 V. On exposure to CYFRA21-1, the ECL decreases because of the immunoreaction between CYFRA21-1 and its antibody which generates a barrier for electron transfer. The determination of CYFRA21-1 with favorable analytical performances was successfully realized under the optimal conditions. ECL decreases linearly in the 1 pg mL-1 to 350 ng mL-1 CYFRA21-1 concentration range, and the detection is as low as 0.3 pg mL-1. Excellent recoveries from CYFRA21-1-spiked human serum indicate that the assay can be operated under physiological conditions. Graphical abstractSchematic representation of the fabrication of molybdenum oxide quantum dots (MoOx QDs) and the electrochemiluminescent (ECL) immunoassay based on the use of the MoOx QDs ECL probe for cytokeratin 19 fragment 21-1 (CYFRA21-1).

Toll-Like Receptor-Mediated Activation of CD39 Internalization in BMDCs Leads to Extracellular ATP Accumulation and Facilitates P2X7 Receptor Activation.

Toll-like receptors (TLRs) trigger innate immune responses through their recognition of conserved molecular ligands of either endogenous or microbial origin. Although activation, function, and signaling pathways of TLRs were already well-studied, their precise function in specific cell types, especially innate immune cells, needs to be further clarified. In this study, we showed that when significantly decreased amounts of membrane CD39, an adenosine triphosphate (ATP)-degrading enzyme, were detected in lipopolysaccharide (LPS)-treated bone marrow-derived dendritic cells (BMDCs), Cd39 mRNA expression, and whole-cell CD39 expression were at the same levels as those in untreated BMDCs. Further experiments demonstrated that the downregulation of membrane CD39 expression in LPS-treated BMDCs was mediated by endocytosis, leading to membrane-exposed CD39 downregulation, which was positively associated with decreased enzymatic activity in ATP metabolism and increased extracellular ATP accumulation. The accumulated ATP promoted intracellular calcium accumulation and IL-1ß production in BMDCs through P2X7 signaling activation. Further research revealed that not only LPS but also other TLR ligands, excluding polyI:C, induced CD39 internalization in BMDCs and that the MyD88 pathway was critical in this process. The results suggested that the activation of CD39 internalization in DCs induced by a TLR ligand caused increased ATP accumulation, leading to P2X7 receptor activation that mediated a proinflammatory effect. Considering the strong modulatory effect of extracellular ATP accumulation on the immune response and inflammation, the manipulation of membrane CD39 expression on DCs may have implications on the regulation and treatment of inflammatory responses.

Outcomes and toxicity of stereotactic body radiation therapy for advanced stage ultra-central non-small cell lung cancer.

BACKGROUND: Previous studies have documented a high incidence of toxicity in patients with ultra-central non-small cell lung cancer (UC-NSCLC) treated with stereotactic body radiation therapy (SBRT). However, these studies mainly focused on early stage patients and included small sample populations. We reviewed the outcomes and toxicity of SBRT in patients with advanced stage UC-NSCLC treated at our institution. METHODS: Fifty-one consecutive patients with advanced UC-NSCLC treated with SBRT using a regular regimen of 35 Gy administered in five fractions between December 2014 and August 2017 were reviewed. UC was defined as tumors abutting or overlapping the trachea or the proximal bronchial tree. We included locally advanced patients who were unfit or unwilling to receive conventional chemoradiotherapy and patients with metastatic or postoperative recurrent disease. Clinical outcomes, dosimetric parameters, and SBRT toxicity were analyzed. RESULTS: The median age was 63 years (range: 35-82), and the median tumor diameter was 6.8 cm (range: 2.1-12.4). The overall median follow-up duration was 17 months (25.5 months for surviving patients). The median local control was 17 months for stage III patients and 11 months for stage IV or recurrent patients. Grade 3 or higher toxicity was observed in 9.8% of patients: G3 radiation pneumonitis (5.9%) and possible treatment-related death (3.9%). CONCLUSION: SBRT with a moderate dose in 4-6 fractions is effective and tolerable for patients with advanced stage UC-NSCLC. However, caution should be taken considering possible treatment-related death. Further studies are warranted.

Facile electrochemiluminescence sensing platform based on water-soluble tungsten oxide quantum dots for ultrasensitive detection of dopamine released by cells.

This report outlines an ultrasensitive electrochemiluminescence (ECL) sensing platform based on water-soluble tungsten oxide quantum dots (WOx QDs) for the detection of dopamine (DA) released from P12 cells. The WOx QDs with good stability and water solubility were prepared by a facile and green hydrothermal method, and used to modify a glassy carbon electrode (WOx QDs/GCE). The proposed ECL sensor exhibited a stable and strong cathodic ECL signal when potassium peroxodisulfate (K2S2O8) as the coreactant in aqueous solution. The possible ECL mechanism was studied and deduced, and the ECL response signal of the proposed sensor decreased rapidly in the presence of dopamine (DA). Under optimal conditions, the ECL signals of WOx QDs linearly decreased with the increase of DA concentration in the range of 10-15 M to 10-9 M and 10-9 M to 10-5 M, respectively. The detection limit was as low as 10-15 M (S/N = 3). Based on these results, this method has been successfully applied to the determination of DA released by PC12 cells. The detection linear range for the detection of DA released by PC12 cells was from 0.1 to 0.9 µM with a detection limit of 0.045 µM. Therefore, the proposed ECL sensor displayed high sensitivity, good specificity and long-term stability, which may shed light on a new way to construct other high-performance ECL detection systems based on WOx or WOx QDs-based nanocomposites.

pNNS-Conjugated Chitosan Mediated IGF-1 and miR-140 Overexpression in Articular Chondrocytes Improves Cartilage Repair.

The aim of the present study was to investigate the effects of phosphorylatable nucleus localization signal linked nucleic kinase substrate short peptide (pNNS)-conjugated chitosan (pNNS-CS) mediated miR-140 and IGF-1 in both rabbit chondrocytes and cartilage defects model. pNNS-CS was combined with pBudCE4.1-IGF-1, pBudCE4.1-miR-140, and negative control pBudCE4.1 to form pDNA/pNNS-CS complexes. Then these complexes were transfected into chondrocytes or injected intra-articularly into the knee joints. High levels of IGF-1 and miR-140 expression were detected both in vitro and in vivo. Compared with pBudCE4.1 group, in vitro, the transgenic groups significantly promoted chondrocyte proliferation, increased glycosaminoglycan (GAG) synthesis, and ACAN, COL2A1, and TIMP-1 levels, and reduced the levels of nitric oxide (NO), MMP-13, and ADAMTS-5. In vivo, the exogenous genes enhanced COL2A1, ACAN, and TIMP-1 expression in cartilage and reduced cartilage Mankin score and the contents of NO, IL-1ß, TNF-α, and GAG contents in synovial fluid of rabbits, MMP-13, ADAMTS-5, COL1A2, and COL10A1 levels in cartilage. Double gene combination showed better results than single gene. This study indicate that pNNS-CS is a better gene delivery vehicle in gene therapy for cartilage defects and that miR-140 combination IGF-1 transfection has better biologic effects on cartilage defects.

Retrospective comparison of stereotactic body radiotherapy versus intensity-modulated radiotherapy for stage III ultra-central squamous non-small-cell lung cancer.

Aim: To analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) versus intensity-modulated radiotherapy (IMRT) in stage III patients with ultra-central squamous non-small-cell lung cancer (sqNSCLC). Methods: Forty-four stage III patients with ultra-central sqNSCLC receiving SBRT (n = 15) or IMRT (n = 29) between December 2014 and August 2017 were reviewed. Results: At a median follow-up of 16.5 months, the 1-year local control rate of SBRT and IMRT was 60.8 and 37.5%, respectively (p = 0.23); the median overall survival was 17 versus 18 months (p = 0.48); ≥3 grade toxicity was 20 versus 24.1% (p = 0.83). Conclusion: SBRT is effective and patient friendly for stage III patients with ultra-central sqNSCLC. Toxicity might be tolerable with a moderate dose five to six fraction regimen. However, more prospective studies are warranted.

Density of bone metastatic lesions increases after radiotherapy in patients with breast cancer.

The aim of this study was to assess local response to radiotherapy (RT) in a quantitative manner by evaluating the bone density of metastases. Spinal and pelvic bone metastases in 44 patients with breast cancer who were treated between May 2010 and December 2016 were retrospectively assessed. Bone density values of irradiated and unirradiated bone metastases before, 1-3 months after, 4-6 months after, and 7-9 months after RT were compared. At each time point, mean bone density ± standard deviation values were measured in Hounsfield units (HU) from computed tomography (CT) scans. Student's t-test was used for statistical analyses of the differences in bone density and for univariate analysis of the prognostic factors for differences in bone density at various time points after RT. Mean bone densities in irradiated and unirradiated bone metastases before RT were 297.31 ± 211.93 HU and 326.29 ± 228.61 HU, respectively. At the subsequent three time points examined, the mean bone density values in the irradiated and unirradiated bone metastases were: 61.97 ± 78.58 HU (P = 0.000) and 36.93 ± 52.49 HU (P = 0.001); 149.07 ± 133.27 HU (P = 0.000) and 68.40 ± 101.10 HU (P = 0.000); and 183.94 ± 168.30 HU (P = 0.000) and 88.21 ± 159.49 HU (P = 0.004), respectively, in each case. Patients receiving bisphosphonates exhibited greater increases in bone density in their metastases 1-3 months after RT (83.04 ± 82.18 HU vs 26.86 ± 60.55 HU, respectively; P = 0.044), whereas chemotherapy before RT was associated with significantly lower increases in bone density at the subsequent three time points [(37.53 ± 67.66 HU vs 93.63 ± 80.36 HU, P = 0.027), (99.30 ± 107.92 HU vs 180.24 ± 127.85 HU, P = 0.030), and (126.07 ± 141.77 HU vs 236.28 ± 158.22 HU, P = 0.024), respectively, in each case]. Comparing bone density values determined from CT scans appears to be a practicable and reproducible method for assessing local response to RT for bone metastasis of breast cancer. Increased bone density was also observed in the irradiated bone metastases.

A panel containing PD-1, IL-2Rα, IL-10, and CA15-3 as a biomarker to discriminate breast cancer from benign breast disease.

Introduction: Programmed cell death protein 1 (PD-1), an immune checkpoint molecule, has recently been recognized as a predictive and prognostic biomarker in several malignant tumors, but its diagnostic value remains largely unknown. We aimed to investigate the differential diagnostic efficiency of PD-1 and other immune molecules and propose a panel of immune molecules combined with cancer antigen 15-3 (CA15-3) to distinguish breast cancer (BC) from benign breast disease (BBD). Patients and methods: Ninety-one eligible BC patients and 31 BBD patients were enrolled. Pretreatment peripheral blood was collected and tested for mRNA expression of PD-1, cytotoxic T lymphocyte antigen 4, forkhead box P3, transforming growth factor beta, interleukin-10 (IL-10), IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 by quantitative reverse transcription PCR. Results: The diagnostic areas under curve (AUCs) of PD-1, IL-2Rα, and IL-10 for BC-BBD discrimination were 0.764, 0.758, and 0.743, respectively. The diagnostic efficiencies of these three parameters in distinguishing early-stage or advanced BC from BBD were consistent with a role in BC-BBD discrimination. A panel of PD-1 + IL-10 + IL-2Rα + CA15-3 showed the highest AUC (0.862), with a sensitivity of 0.933 and a specificity of 0.724, for BC-BBD discrimination. In addition, for early-stage BC discrimination, this panel also had the highest AUC (0.811), with a sensitivity of 0.933 and a specificity of 0.614, while for advanced BC discrimination, a panel of PD-1 + IL-10 + CA15-3 exhibited the highest AUC (0.896), with a sensitivity of 0.933 and a specificity of 0.783. Conclusion: These data indicate that the panel containing PD-1, IL-2Rα, IL-10, and CA15-3 can effectively discriminate BC from BBD with a high efficiency. After further confirmation, it could be used to complement conventional imaging modalities, especially in discriminating early-stage BC from BBD.

Albumin/globulin ratio is negatively correlated with PD-1 and CD25 mRNA levels in breast cancer patients.

BACKGROUND: Previous studies have demonstrated the prognostic value of globulin (GLB), albumin (ALB), the ALB/GLB ratio (AGR), body mass index (BMI), hemoglobin (Hb), and prognostic nutritional index (PNI) in breast cancer. The underlying mechanism has been investigated by examining the impact of nutritional parameters on T cells, natural killer cells, and dendritic cells, but little is known about their effect on checkpoint molecules. METHODS: Here, we investigated the correlation of mRNA expression of programmed cell death protein 1 (PD-1), cluster of differentiation 28 (CD28), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and cluster of differentiation 25 (CD25) with AGR, ALB, GLB, total protein, pre-ALB, Hb, BMI, and PNI in the peripheral blood of breast cancer patients. One hundred and three patients and 21 age- and sex-matched healthy controls were enrolled. Quantitative real-time PCR was used to test relative mRNA expression. RESULTS: The results indicated that the mRNA levels of PD-1 and CD25 were 5.2- and 3.3-fold higher in patients with low AGR than in those with high AGR (P < 0.05). The mRNA levels of PD-1 were 3.5-fold higher in patients with high GLB than in those with low GLB (P < 0.05). In addition, breast cancer patients had higher expression levels of PD-1, CD28, CTLA-4, and CD25 mRNA in their peripheral blood compared with healthy volunteers (P < 0.05). CONCLUSION: These results suggest that AGR is negatively correlated with PD-1 and CD25 mRNA levels, while GLB is positively associated with PD-1 mRNA levels. Nutritional status in breast cancer patients may influence the PD-1 pathway and have implications for the optimization of cancer therapy.