Self-Delivery Nanoplatform Based on Amphiphilic Apoptosis Peptide for Precise Mitochondria-Targeting Photothermal Therapy.

Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.

Hyperthermia is a promising potential adjunct to treating sporotrichosis: A refractory case of HIV sporotrichosis and in vitro experiments on Sporothrix spp.

BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.

Temporal gene expression profiling during early-stage traumatic temporomandibular joint bony ankylosis in a sheep model.

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.

Tissue-specific transcriptome and metabolome analyses reveal candidate genes for lignan biosynthesis in the medicinal plant Schisandra sphenanthera.

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes.

Effects of resveratrol on macrophages after phagocytosis of Candida glabrata.

Candida glabrata is believed to be the underlying cause of many human ailments, including oral, gastrointestinal, and vaginal disorders. C. glabrata-caused deep-seated infections, coupled with its resistance to antifungal drugs, may contribute to a high mortality rate. Resveratrol is a polyphenol and can achieve better therapeutic effects when administered in combination with micafungin, but the underlying molecular mechanisms remain unknown. Here, we investigate the effects of varying doses of resveratrol on the proliferation, apoptosis, and activity of macrophages, which were co-cultured with micafungin-pretreated C. glabrata. Resveratrol can restore the decreased proliferative activity of macrophages caused by the phagocytosis of C. glabrata. Further investigations demonstrated that this restoration ability exhibited a dose-dependent manner, reaching the highest level at 200 µM of resveratrol. Resveratrol tended to be more effective in inhibiting macrophage apoptosis and reducing reactive oxygen species (ROS) levels with concentration increases. In addition, at medium concentrations, resveratrol may down-regulate the expression of most inflammatory cytokines, whereas at high concentrations, it started to exert pro-inflammatory functions by up-regulating their expressions. Macrophages may shift from an anti-inflammatory (M2) phenotype to an inflammatory (M1) phenotype by resveratrol at 200 µM, and from M1 to M2 at 400 µM. Our research shows that resveratrol with micafungin are effective in treating C. glabrata infections. The resveratrol-micafungin combination can reduce the production of ROS, and promote the proliferation, inhibit the apoptosis, and activate the polarization of macrophages in a dose-dependent manner. This study offers insights into how this combination works and may provide possible direction for further clinical application of the combination.

Optical Control of Multistage Phase Transition via Phonon Coupling in MoTe_{2}.

The temporal characters of laser-driven phase transition from 2H to 1T^{'} has been investigated in the prototype MoTe_{2} monolayer. This process is found to be induced by fundamental electron-phonon interactions, with an unexpected phonon excitation and coupling pathway closely related to the nonequilibrium relaxation of photoexcited electrons. The order-to-order phase transformation is dissected into three substages, involving energy and momentum scattering processes from optical (A_{1}^{'} and E^{'}) to acoustic phonon modes [LA(M)] in subpicosecond timescale. An intermediate metallic state along the nonadiabatic transition pathway is also identified. These results have profound implications on nonequilibrium phase engineering strategies.

Arabidopsis MYB4 plays dual roles in flavonoid biosynthesis.

Flavonoids are major secondary metabolites derived from the plant phenylpropanoid pathway that play important roles in plant development and also have benefits for human health. So-called MBW ternary complexes involving R2R3-MYB and basic helix-loop-helix (bHLH) transcription factors along with WD-repeat proteins have been reported to regulate expression of the biosynthetic genes in the flavonoid pathway. MYB4 and its closest homolog MYB7 have been suggested to function as repressors of phenylpropanoid metabolism. However, the detailed mechanism by which they act has not been fully elucidated. Here, we show that Arabidopsis thaliana MYB4 and its homologs MYB7 and MYB32 interact with the bHLH transcription factors TT8, GL3 and EGL3 and thereby interfere with the transcriptional activity of the MBW complexes. In addition, MYB4 can also inhibit flavonoid accumulation by repressing expression of the gene encoding Arogenate Dehydratase 6 (ADT6), which catalyzes the final step in the biosynthesis of phenylalanine, the precursor for flavonoid biosynthesis. MYB4 potentially represses not only the conventional ADT6 encoding the plastidial enzyme but also the alternative isoform encoding the cytosolic enzyme. We suggest that MYB4 plays dual roles in modulating the flavonoid biosynthetic pathway in Arabidopsis.

Melanin of Sporothrix globosa affects the function of THP-1 macrophages and modulates the expression of TLR2 and TLR4.

BACKGROUND: Melanin is an important virulence factor for Sporothrix globosa, the causative agent of sporotrichosis, a subcutaneous mycosis that occurs worldwide. Although previous research suggests that melanin is involved in the pathogenesis of sporotrichosis, little is known about its influence on the macrophages that represent the frontline components of innate immunity. OBJECTIVES: To evaluate the effects of melanin on phagocytic activity and the expression of Toll-like receptor (TLR)2 and TLR4 during S. globosa infection of macrophages in vitro. METHODS: To compare phagocytic activity and survival rates, THP-1 macrophages and primary mouse peritoneal macrophages were co-cultured with a wild-type S. globosa strain (Mel+), an albino mutant strain (Mel-), a tricyclazole-treated Mel + strain (TCZ-Mel+), or melanin ghosts extracted from S. globosa conidia. Reactive oxygen species (ROS), nitric oxide (NO) generation, tumor necrosis factor (TNF)-α and interleukin (IL)-6 were assayed in THP-1 cells infected with S. globosa conidia. Quantitative PCR and western blotting were used to observe the effect of melanin on TLR2 and TLR4 expression. Knockdown of TLR2/4 expression with small interfering RNA was performed to further verify the role of these receptors during infection. RESULTS: Macrophages infected with Mel + conidia showed a lower phagocytosis index and a higher survival rate than TCZ-Mel+ and Mel- in vitro. After incubation with S. globosa, the release of ROS, NO, TNF-α and IL-6 by THP-1 were decreased in the presence of melanin. Increased mRNA and protein expression of TLR2 and TLR4 occurred upon S. globosa infection in THP-1, whereas the presence of melanin suppressed TLR2 and TLR4. Moreover, TLR2 or TLR4 knockdown showed a trend toward reducing the pernicious effect of S. globosa conidia on THP-1 cells in vitro. CONCLUSIONS: Collectively, our results indicated that melanin inhibits the phagocytosis of S. globosa and guards against macrophage attack by providing protection from oxygen- and nitrogen-derived radicals, as well as suppressing the host pro-inflammatory cytokine response (TNF-α and IL-6). Melanin was also involved in modulating TLR2 and TLR4 receptor expression, weakening the killing efficiency of S. globosa.

Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.

Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).

Absorbance or organization into ankylosis: a microarray analysis of haemarthrosis in a sheep model of temporomandibular joint trauma.

BACKGROUND: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. MATERIAL/METHODS: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. RESULTS: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-ß), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. CONCLUSIONS: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.

[Role and mechanism of histone deacetylases in mouse neuronal development].

OBJECTIVE: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development. METHODS: The mice with Synapsin1-Cre recombinase were bred with HDAC1&2flox/flox mice to obtain the mice with neuron-specific HDAC1&2 conditional knockout (knockout group), and their littermates without HDAC1&2 knockout were used as the control group. The general status of the mice was observed and survival curves were plotted. Brain tissue samples were collected from the knockout group and the control group. Western blot and immunohistochemistry were used to measure the protein expression of related neuronal and axonal markers, neuronal nuclear antigen (NeuN), non-phosphorylated neurofilament heavy chain (np-NF200), and phosphorylated neurofilament heavy chain (p-NF200), as well as the downstream effector of the mTOR signaling pathway, phosphorylated S6 ribosomal protein (p-S6). RESULTS: The mice with HDAC1&2 conditional knockout usually died within one month after birth and were significantly smaller than those in the control group, with motor function abnormalities such as tremor and clasping of hindlimbs. Compared with the control group, the knockout group had significant reductions in the protein expression levels of NeuN, np-NF200, p-NF200, and p-S6 (P < 0.05; n=3). CONCLUSIONS: Deletion of HDAC1 and HDAC2 in mouse neurons results in reduced neuronal maturation and axonal dysplasia, which may be associated with the mTOR signaling pathway.

Changes in axial length after orthokeratology lens treatment for myopia: a meta-analysis.

PURPOSE: Orthokeratology (OK) lens is a popular optical method to control myopia progression. This study aimed to assess the effect of OK lens on axial length change compared with glasses. METHODS: PubMed, Web of Science, and Embase were searched to retrieve the related articles. Then, the articles were selected according to predefined criteria. Standardized mean difference (SMD) and 95% confidence interval (CI) were selected as effect size for combining and analyzing the change in axial length. RESULTS: A total of 13 articles were included in the present study. Different models were selected according to the heterogeneity of each analysis. The axial length change in OKs group was significantly smaller than control group; SMD (95% CI) of change in axial length was - 0.857 (- 1.146, - 0.568), p < 0.001 at the end of 1 year and - 0.701 (- 1.675, 0.272), p < 0.001 at the end of 2 years or longer time. CONCLUSIONS: OK lens treatment appears more effective in slowing axial elongation than glasses during the early treatment of myopia in children.

Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel.

Despite improvements in the prognosis of osteosarcoma patients, chemotherapy fails in a considerable number of cases due to drug resistance. The development of novel agents may enhance chemosensitivity. This study explored the anticancer function of polydatin and its ability-in combination with paclitaxel-to overcome drug resistance in human osteosarcoma U-2OS and MG-63 cell lines. A cell proliferation assay (celll counting kit-8), a cell-cycle assay, an apoptosis assay (annexin V-fluorescein isothiocyanate/propidium iodide), and a cell migration assay (Transwell) were used to analyze cell activity. Western blot analysis and quantitative reverse-transcription polymerase chain reaction were performed to examine function-related mRNA and protein levels. Treatment with polydatin suppressed cell growth and migration in both cell lines. Moreover, polydatin induced cell apoptosis in both parental and paclitaxel-resistant cells, and cell-cycle arrest in the S phase. Furthermore, it altered the expression of various proteins associated with cell growth (Ki67, p21, cyclin A, cyclin E, and cyclin-dependent kinase 2), migration (matrix metalloproteinase-2 [MMP-2], MMP-9, and tissue inhibitor of metalloproteinase-1), apoptosis (poly[ADP-ribose] polymerase 1 and caspase 3), and drug resistance (p-glycoprotein 1, lung resistance-related protein 1, growth arrest and DNA damage-45α, glutathione S-transferase π, and heat shock protein 27) in paclitaxel-resistant osteosarcoma cells. Cells transfected with myr-Akt caused obvious upregulation and activation of Akt, which were significantly attenuated via polydatin treatment. In conclusion, polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel.

Locating Hazardous Chemical Leakage Source Based on Cooperative Moving and Fixing Sensors.

In dealing with sudden hazardous chemical leakage accidents, the key to solving the evacuation and transfer of personnel and important property is to determine the location of the leakage source and the information of the source strength to gauge the scope of the impact of leakage. The particle swarm optimization algorithm with an adaptive mutation factor is applied to the inverse calculation of leakage source strength to obtain the leakage source information, and the leakage source location problem is transformed into an optimization problem. The mobile sensor is then introduced into the fixed sensor network. The mobile sensor moving strategy based on an extended Kalman filter is proposed. The estimated value of the previous moment and the current time are used to update the estimation of the state variable, and then the mobile strategy is planned. The interference of the random error of the optimization algorithm on the path planning of the mobile sensor is reduced by introducing the optimized result memory and, thus, location efficiency is improved. Simulation results showed that the proposed method, which combines mobile with fixed sensors, greatly expanded the monitoring function of the network, reduced the number of fixed sensors, and enhanced the positioning accuracy.

Impact of fenofibrate on choroidal neovascularization formation and VEGF-C plus VEGFR-3 in Brown Norway rats.

OBJECTIVE: This study aims to explore the possible role of fenofibrate in inhibiting choroidal neovascularization (CNV) in Brown Norway (BN) rats. METHODS: BN rats underwent binocular retinal laser photocoagulation to induce CNV. On day one, fenofibrate was injected into the vitreous cavity of rats in the control and experimental groups. Fundus fluorescein angiography (FFA), isolectin B4-FITC staining, immunofluorescence staining, qRT-PCR and western blot were performed at 1, 2, 3 and 4 weeks to observe the morphological changes of CNV and the expression of the vascular endothelial growth factor C (VEGF-C) and the vascular endothelial growth factor receptor-3 (VEGFR-3). RESULTS: CNV with the spontaneous gradual regression and scarring phenomenon appeared in BN rats. In neovascularization, VEGF-C was mainly distributed in the ganglion cell layer, while VEGFR-3 was mainly expressed in the choroid. In the control group, choroidal VEGF-C initially increased, and subsequently decreased, while VEGFR-3 level maintained a constant level after the decrease. Both had a decreasing expression in the retina. The early formation of CNV was significantly weakened in the experimental group, but there was no difference in the later period. VEGF-C and VEGFR-3 expression in the choroid and retina were lower than in the control group. Furthermore, VEGFR-3 protein was not expressed in the retina. However, this gradually increased in the early period and declined in the terminal stage in the choroid. CONCLUSION: VEGF-C and VEGFR-3 participated in the laser-induced CNV formation in BN rats. Fenofibrate could inhibit CNV formation.

Momentum-resolved TDDFT algorithm in atomic basis for real time tracking of electronic excitation.

Ultrafast electronic dynamics in solids lies at the core of modern condensed matter and materials physics. To build up a practical ab initio method for studying solids under photoexcitation, we develop a momentum-resolved real-time time dependent density functional theory (rt-TDDFT) algorithm using numerical atomic basis, together with the implementation of both the length and vector gauge of the electromagnetic field. When applied to simulate elementary excitations in two-dimensional materials such as graphene, different excitation modes, only distinguishable in momentum space, are observed. The momentum-resolved rt-TDDFT is important and computationally efficient for the study of ultrafast dynamics in extended systems.

Comparison of intravitreal triamcinolone acetonide versus intravitreal bevacizumab as the primary treatment of clinically significant macular edema.

OBJECTIVES: To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings. METHODS: Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups. RESULTS: In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (P > 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (P > 0.05). CONCLUSION: The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA.

[Lymph node metastasis and prognostic analysis of 354 cases of T1 breast cancer].

OBJECTIVE: To analyze the characteristics of lymph node metastasis and prognosis in patients with T1 breast cancer. METHODS: The clinicopathological data of 354 patients with T1 breast cancer after standard treatment from March 2007 to September 2011 were collected to analyze the relationship between the clinical characteristics of T1 breast cancer, lymph node metastasis and prognostic features. RESULTS: In the 354 patients with T1 breast cancer, 105 patients (29.7%) had lymph node metastasis, among them 73 cases (69.5%) had 1-3 lymph node metastasis, and 32 cases (30.5%) had more than 4 lymph node metastasis. The lymph node metastasis rate was 8.3% in T1a patients, 39.7% in T1b patients, and 30.4% in T1c cases (P = 0.005). Pairwise comparison showed that the difference of lymph node metastasis rate between T1a, T1b and T1c patients was statistically significant (P = 0.001 and P = 0.006, respectively). The difference of lymph node metastasis rates in T1b and T1c patients was statistically insignificant (P = 0.171). In the 354 patients of T1 breast cancer, 92 patients had vascular tumor thrombi and their lymph node metastasis rate was 71.7%, while the lymph node metastasis rate in 262 patients without vascular tumor thrombus was 14.9% (P < 0.001). The median follow-up was 49 months (range 27-81 months). 12 patients developed recurrence, and 3 patients died, one of them died of cerebrovascular accident. The 4-year disease-free survival for all patients was 96.6%, and the 4-year overall survival rate was 99.2%. CONCLUSIONS: There is a correlation between vascular tumor thrombus, tumor size and lymph node metastasis rate. The lymph node metastasis rate is lower in T1a patients and relatively higher in T1b/c patients. Compared with patients without vascular tumor thrombus, the T1 breast cancer patients with vascular tumor thrombi have a higher lymph node metastasis rate. Generally speaking, there is a still good prognosis in patients with T1 breast cancer.

Chemokine systems in oncology: From microenvironment modulation to nanocarrier innovations.

Over the past few decades, significant strides have been made in understanding the pivotal roles that chemokine networks play in tumor biology. These networks, comprising chemokines and their receptors, wield substantial influence over cancer immune regulation and therapeutic outcomes. As a result, targeting these chemokine systems has emerged as a promising avenue for cancer immunotherapy. However, therapies targeting chemokines face significant challenges in solid tumor treatment, due to the complex and fragile of the chemokine networks. A nuanced comprehension of the complicacy and functions of chemokine networks, and their impact on the tumor microenvironment, is essential for optimizing their therapeutic utility in oncology. This review elucidates the ways in which chemokine networks interact with cancer immunity and tumorigenesis. We particularly elaborate on recent innovations in manipulating these networks for cancer treatment. The review also highlights future challenges and explores potential biomaterial strategies for clinical applications.

Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials.

Objectives: To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma. Methods: Systematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria. Results: A total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P<0.05), progression-free survival (HR=0.69, 95% CI: 0.54-0.87, P<0.05), complete response rate (Risk Ratio [RR]=1.52, 95% CI: 1.24-1.86, P<0.05), and objective response rate (RR=1.32, 95% CI: 1.17-1.48, P<0.05) were significantly improved in the nimotuzumab combination treatment group compared with the control group. In terms of the incidence of adverse effects, only the incidence of rash was the nimotuzumab combination group higher than in the treatment alone group, and there was no significant difference between the remaining adverse reactions (neutropenia, anemia, nausea/vomiting, mucositis, dermatitis, dysphagia). Conclusion: Nimotuzumab combined with radiotherapy or chemoradiotherapy is more effective than radiotherapy alone or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck, and the safety profile is controllable. Therefore, the addition of nimotuzumab to treatment is expected to be an effective treatment option for this disease. However, more prospective randomized controlled trials are needed to fully explore the effectiveness of this treatment in patients with locally advanced head and neck squamous cell carcinoma. Systematic Review Registration: identifier PROSPERO (CRD: 42022383313).