The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Overcoming the limitations of immunotherapy in pancreatic ductal adenocarcinoma: Combining radiotherapy and metabolic targeting therapy.

As a novel anticancer therapy, immunotherapy has demonstrated robust efficacy against a few solid tumors but poor efficacy against pancreatic ductal adenocarcinoma (PDAC). This poor outcome is primarily attributable to the intrinsic cancer cell resistance and T-cell exhaustion, which is also the reason for the failure of conventional therapy. The present review summarizes the current PDAC immunotherapy avenues and the underlying resistance mechanisms. Then, the review discusses synergistic combination therapies, such as radiotherapy (RT) and metabolic targeting. Research suggests that RT boosts the antigen of PDAC, which facilitates the anti-tumor immune cell infiltration and exerts function. Metabolic reprogramming contributes to restoring the exhausted T cell function. The current review will help in tailoring combination regimens to enhance the efficacy of immunotherapy. In addition, it will help provide new approaches to address the limitations of the immunosuppressive tumor microenvironment (TME) by examining the relationship among immunotherapy, RT, and metabolism targeting therapy in PDAC.

Pyruvate Kinase M2 Nuclear Translocation Regulate Ferroptosis-Associated Acute Lung Injury in Cytokine Storm.

Cytokine storm (CS) is linked with macrophage dysfunction and acute lung injury (ALI), which can lead to patient mortality. Glycolysis is preferentially exploited by the pro-inflammatory macrophages, in which pyruvate kinase M2 (PKM2) is a critical enzyme. The mechanism underlying the link between CS and ALI involves cell death, with the recently discovered programmed cell death known as ferroptosis being involved. However, the relationship between the glycolysis and ferroptosis in the context of CS-related ALI remains unclear. CS-associated ALI induced by poly I:C (10 mg/kg, i.v) and LPS (5 mg/kg, i.p) (IC: LPS) exhibit significant ferroptosis. Ferrostatin-1 (ferroptosis inhibitor) treatment attenuated IC:LPS­induced mortality and lung injury. Moreover, Alveolar macrophage (AM) from IC:LPS model exhibited enhanced glycolysis and PKM2 translocation. The administration of ML-265(PKM2 monomer/dimer inhibitor) resulted in the formation of a highly active tetrameric PKM2, leading to improved survival and attenuation of ALI. Furthermore, ML-265 treatment decreased ferroptosis and restored the balance between anaerobic glycolysis and oxidative phosphorylation. Notably, in patients with lung infection, intracellular expression level of PKM2 were correlated with circulating inflammation. Enhanced ferroptosis and PKM2 nuclear translocation was noticed in CD14+ blood monocytes of lung infection patients with CS. In conclusion, PKM2 is a key regulatory node integrating metabolic reprograming with intra-nuclear function for the regulation of ferroptosis. Targeting PKM2 could be explored as a potential means in the future to prevent or alleviate hyper-inflammatory state or cytokines storm syndrome with aberrant ferroptotic cell death.

Significantly Tunable Foaming Behavior of Blowing Agent for the Polyethylene Foam Resin with a Unique Designed Blowing Agent System.

The chemical blowing agent plays a crucial role in enhancing the performance of the polyethylene (PE) foaming resin during the rotational foaming process. Previously, the conventional blowing agent of the PE resin commonly used pure azodicarbonamide (AZ). It had the unavoidable drawbacks of releasing NH3 and exhibiting strong reactions during the rotational foaming process. Meantime, pure AZ had a relatively high decomposition temperature, resulting in a sharp foaming process. To address the above issues, this work developed a uniquely designed blowing agent system. In this study, a novel blowing agent for the PE resin was successfully synthesized by a one-pot method. This blowing agent consisted of an activator and AZ, which exhibited a lower decomposition temperature and a milder decomposition rate than AZ. The activator was constituted of small-sized ammonium dihydrogen phosphate on the AZ surface, which could be decomposed properly and deliver phosphoric acid and H2O during the foaming process. Then, AZ reacted with H2O under phosphoric acid catalysis. Also, this reaction generated CO2 emission while reducing the emission of NH3 through recombination with phosphoric acid. Moreover, phosphoric acid catalysis caused a decrease in the AZ decomposition temperature. Meantime, the thermal coupling appeared during the foaming process, which could further reduce the decomposition rate. Consequently, the small activator played a key role in regulating cell formation and diffusion. Compared to AZ, the novel blowing agent system significantly reduced the cell diameter of the PE foam resin and enhanced its flexural modulus by 50%. Furthermore, the novel blowing agent facilitated better demolding performance and improved the surface morphology of the PE foam product. This research provides significant foaming behavior regulation for the PE resin during industrial applications.

NKX2-1-AS1 promotes the lymphangiogenesis of lung adenocarcinoma through regulation of ERG-mediated FABP4.

Lymphatic metastasis is a common metastasis of lung adenocarcinoma (LUAD). The current study illustrated the action of lncRNA NKX2-1-AS1 in lymphangiogenesis in LUAD and the underlying mechanisms. Clinical tissue samples were collected for determining NKX2-1-AS1 expression. Then, H441 and H661 cells were selected to perform gain- and loss-of-function assays for dissecting the roles of NKX2-1-AS1 in LUAD cell proliferation and migration. Besides, H441 and H661 cell supernatant was harvested to stimulate HLECs for assessing tube formation ability. Interaction among NKX2-1-AS1, ERG, and fatty acid binding protein 4 (FABP4) was validated through luciferase and RIP assays. NKX2-1-AS1 was highly-expressed in LUAD tissues. Silencing NKX2-1-AS1 suppressed H441 and H661 cell proliferation and migration, reduced expression levels of lymphangiogenesis-related factors (LYVE-1, VEGF-C, VEGFR3, VEGF-A, VEGFR2, and CCR7), and inhibited HLEC tube formation. Interaction validation demonstrated that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG. Overexpression of FABP4 could effectively block the inhibition role of NKX2-1-AS1 silencing in lymphangiogenesis in H441 and H661 cells. This study provided evidence that NKX2-1-AS1 regulated FABP4 transcription by binding to ERG to facilitate the proliferation and migration of LUAD cells and tube formation of HLECs, thus participating in lymphangiogenesis.

Combination of Palbociclib and Endocrine Therapy in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer With or Without Brain Metastases.

OBJECTIVE: This real-world study aimed to investigate the efficacy and safety of palbociclib plus endocrine therapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in the real world in a Chinese population. METHODS: The clinical data of consecutively enrolled patients from the Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, and the University of Hong Kong - Shenzhen Hospital were collected. Progression-free survival curves were generated using log-rank tests with the Kaplan-Meier method. Univariate and multivariate logistic regression analyses were performed to identify the factors affecting progression-free survival. RESULTS: In total, 118 patients were enrolled, including 6 patients with brain metastases. At the last follow-up date, the median progression-free survival was 16.8 months (95% confidence interval, 11.1-22.5), with the 6-month and 12-month progression-free survival rates of 77.1% and 57.6%, respectively. The disease control rate and the intracranial disease control rate were 82.2% and 50%, respectively. A longer progression-free survival was observed for patients with the following characteristics: treatment-naive; without hepatic metastasis; sensitive to previous endocrine therapy and harboring fewer metastatic sites. The multivariate logistic regression analysis demonstrated that treatment lines and exposure to palliative chemotherapy were independent influencing factors of progression-free survival. CONCLUSIONS: Palbociclib plus endocrine therapy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer was effective and well-tolerated, even in patients with brain metastases. More benefits were observed in frontline therapy, chemotherapy-naive, and endocrine therapy-sensitive patients with fewer metastatic sites.

Hydrogen Bonds Reinforced Ionogels with High Sensitivity and Stable Autonomous Adhesion as Versatile Ionic Skins.

Flexible wearable sensors have demonstrated enormous potential in various fields such as human health monitoring, soft robotics, and motion detection. Among them, sensors based on ionogels have garnered significant attention due to their wide range of applications. However, the fabrication of ionogels with high sensitivity and stable autonomous adhesion remains a challenge, thereby limiting their potential applications. Herein, we present an advanced ionogel (PACG-MBAA) with exceptional performances based on multiple hydrogen bonds, which is fabricated through one-step radical polymerization of N-acryloylglycine (ACG) in 1-ethyl-3-methylimidazolium ethyl sulfate (EMIES) in the presence of N,N'-methylenebis(acrylamide) (MBAA). Compared with the ionogel (PAA-MBAA) formed by polymerization of acrylic acid (AA) in EMIES, the resulting ionogel exhibits tunable mechanical strength (35-130 kPa) and Young's modulus comparable to human skin (60-70 kPa) owing to the multiple hydrogen bonds formation. Importantly, they demonstrate stable autonomous adhesion to various substrates and good self-healing capabilities. Furthermore, the ionogel-based sensor shows high sensitivity (with a gauge factor up to 6.16 in the tensile range of 300-700%), enabling the detection of both gross and subtle movements in daily human activities. By integration of the International Morse code, the ionogel-based sensor enables the encryption, decryption, and transmission of information, thus expanding its application prospects.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Ovarian cancer classification and prognosis assessment model based on prognostic target genes in key microRNA-target gene networks.

BACKGROUND: The present study was designed to screen key microRNA (miRNA)-target gene networks for ovarian cancer (OC) and to classify and construct a risk assessment system for OC based on the target genes. METHODS: OC sample data of The Cancer Genome Atlas dataset and GSE26193, GSE30161, GSE63885 and GSE9891 datasets were retrospectively collected. Pearson correlation analysis and targeted analysis of miRNA and target gene were performed to screen key miRNA-target gene networks. Target genes associated with the prognosis of OC were screened from key miRNA-target gene networks for consensus clustering and least absolute shrinkage and selection operator-based regression machine learning analysis of OC samples. RESULTS: Twenty target genes of 2651 key miRNA-target gene pairs had significant prognostic correlation in each OC cohort, and OC was divided into three clusters. There were differences in prognostic outcome, biological pathways, immune cell abundance and susceptibility to immune checkpoint blockade (ICB) therapy and anti-tumor drugs among the three molecular clusters. S2 exhibited the least advantage in prognosis and immunotherapy response rate in the three molecular clusters, and the pathways regulating immunity, hypoxia, metabolism and promoting malignant progression of cancer, as well as infiltrating immune and stromal cell population abundance, were the highest in this cluster. An eight-target gene prognostic model was created, and the risk index obtained by using this model not only significantly distinguished the immune characteristics of the sample, but also predicted the response of the sample to ICB treatment, and helped to screen 36 potential anti-OC drugs. CONCLUSIONS: The present study provides a classification strategy for OC based on prognostic target genes in key miRNA-target gene networks, and creates a risk assessment system for predicting prognosis and response to ICB therapy in OC patients, providing molecular basis for prognosis and precise treatment of OC.

Febrile seizure in children with COVID-19 during the Omicron wave.

Objective: To explore the clinical characteristics and prognosis of febrile seizure in children with COVID-19. Methods: This study is a single-center retrospective cohort study. The cases included febrile seizures in children with COVID-19 admitted to the Renji Hospital from April 7th, 2022 to June 2nd, 2022. We compared children with and without febrile seizures in their clinical characteristics such as sex, age, symptoms, seizure manifestation, COVID-19 severity, and SARS-CoV-2 nucleic acid test results. The children with febrile seizures were followed up by telephone and outpatient service about one month after the nucleic acid turned negative and discharged from the hospital. Results: A total of 585 cases of children with COVID-19 were included in the analysis. There were 15 children (1.8%) with febrile seizures, age from six months to three years old, nine boys (60.0%) and six girls (40.0%). The manifestations of febrile seizures were all generalized tonic-clonic seizures. The median nucleic acid negative conversion time was 11 (IQR:10.75,13) days. Our first comparison involved comparing children without underlying diseases; there was no significant difference in sex, COVID-19 severity, and clinical manifestations, but there was an age difference (2 vs. 1.3, P = 0.047). There was no difference in SARS-CoV-2 nucleic acid negative time between the two groups (11d vs. 13d, P = 0.128). One child had new clinical manifestations during the follow-up, but his EEG and MRI were normal. Conclusion: Febrile seizure may be children's primary neurological manifestation of COVID-19. It may occur in children with no history of epilepsy and is not associated with severe illness. The long-term neurological outcomes of these children should be followed up.

Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

PURPOSE: Our preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen. PATIENTS AND METHODS: Patients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on Days 1, 2, 8, 9, 15, and 16. Patients received 40 mg Dex and 1.5 mg/m2 BZ on Days 1, 8, and 15. Cycles were repeated every 28 days. Pre- and posttreatment bone marrow specimens (IHC, n = 9; imaging mass cytometry, n = 6) and peripheral blood samples were collected for analysis (flow cytometry, n = 5; T-cell receptor clonality, n = 7; cytokine assay, n = 7). RESULTS: PELA/BZ/Dex was well-tolerated in all patients. Treatment-emergent toxicities were transient, and no dose-limiting toxicities occurred. Six (55%) of 11 response-evaluable patients showed decreased paraprotein. Treatment increased T and natural killer cell activation, inflammatory cytokine release, and programmed death-ligand 1 expression in bone marrow. Compared with nonresponders, responders had higher reovirus protein levels, increased cytotoxic T-cell infiltration posttreatment, cytotoxic T cells in significantly closer proximity to multiple myeloma cells, and larger populations of a novel immune-primed multiple myeloma phenotype (CD138+ IDO1+HLA-ABCHigh), indicating immunomodulation. CONCLUSIONS: PELA/BZ/Dex is well-tolerated and associated with anti-multiple myeloma activity in a subset of responding patients, characterized by immune reprogramming and TiME changes, warranting further investigation of PELA as an immunomodulator.

Corrigendum: Different immunological mechanisms between AQP4 antibody-positive and MOG antibody-positive optic neuritis based on RNA sequencing analysis of whole blood.

[This corrects the article DOI: 10.3389/fimmu.2023.1095966.].

Effect of cognitive behavioral group therapy on rehabilitation of community patients with schizophrenia: A short-term randomized control trial.

BACKGROUND: The efficacy of cognitive behavioral group therapy (CBGT) for cognitive dys-function and negative symptoms of schizophrenia is established, but more evidence is required. AIM: To assess the effectiveness of CBGT combined with mental health education as a treatment for schizophrenia compared with mental health education alone. METHODS: In all, 120 schizophrenia out-patients were randomized into CBGT combined with mental health education or single mental health education. The primary outcomes were positive and negative symptoms, cognitive function, excitatory factor, anxiety and depression symptom improvements on the positive and negative syndrome scale score. Secondary outcome measures included social function and drug compliance. RESULTS: There were significant differences between CBGT combined with mental health education and single mental health education on measures of positive and negative symptoms, cognitive functions, excitatory factor, anxiety and depression symptoms, and social functions. No other significant difference in outcomes was observed. CONCLUSION: CBGT combined with mental health education may be relevant beneficial treatment method in reducing symptoms, cognitive and social functions of patients with schizophrenia.

Breast cancer metastases to the thyroid and stomach: A case report.

The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (-), progesterone receptor (-), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner.

C-C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by accelerated lipid deposition, aberrant inflammation, and excessive extracellular matrix production in the liver. Short of effective intervention, NAFLD can progress to cirrhosis and hepatocellular carcinoma. In the present study we investigated the involvement of the C-C motif ligand 11 (CCL11) in NAFLD pathogenesis. Methods: NAFLD was induced by feeding mice with a high-fat high-carbohydrate diet. CCL11 targeting was achieved by genetic deletion or pharmaceutical inhibition. The transcriptome was analysed using RNA-seq. Results: We report that CCL11 expression was activated at the transcription level by free fatty acids (palmitate) in hepatocytes. CCL11 knockdown attenuated whereas CCL11 treatment directly promoted production of pro-inflammatory/pro-lipogenic mediators in hepatocytes. Compared with wild-type littermates, CCL11 knockout mice displayed an ameliorated phenotype of NAFLD when fed a high-fat high-carbohydrate diet as evidenced by decelerated body weight gain, improved insulin sensitivity, dampened lipid accumulation, reduced immune cell infiltration, and weakened liver fibrosis. RNA-seq revealed that interferon regulatory factor 1 as a mediator of CCL11 induced changes in hepatocytes. Importantly, CCL11 neutralisation or antagonism mitigated NAFLD pathogenesis in mice. Finally, a positive correlation between CCL11 expression and NAFLD parameters was identified in human patients. Conclusions: Our data suggest that CCL11 is a novel regulator of NAFLD and can be effectively targeted for NAFLD intervention. Impact and implications: Non-alcoholic fatty liver disease (NAFLD) precedes cirrhosis and hepatocellular carcinoma. In this paper we describe the regulatory role of CCL11, a C-C motif ligand chemokine, in NAFLD pathogenesis. Our data provide novel insights and translational potential for NAFLD intervention.

Surface Modification of Cyclic-Olefin-Copolymer (COC)-Based Microchannels for the Large-Scale Industrial Production of Droplet Microfluidic Devices.

The copolymers of cycloolefin (COC), a type of thermoplastic material, have been widely used for the large-scale industrial fabrication of droplet microfluidic devices, which is often performed using hot-embossing or injection-molding techniques. The generation of droplets and the uniformity of droplet sizes are significantly affected by the surface wettability of COC during fabrication and the pressure stability of the employed fluid pump during operation. In order to alleviate the effects of undesirable surface wettability and pressure variation on the generation of droplets in COC-based devices, a simple surface modification procedure was applied to hydrophobically modify the surfaces of COC-based microchannels for large-scale industrial production. The surface modification procedure consisted of an oxygen plasma treatment of the polymer surface followed by a solution-phase reaction in fluorocarbon solvent. The experimental results demonstrate that following the proposed surface modification, the COC droplet microfluidic devices could stably generate microvolume water droplets with a small coefficient of variation, even if the pressure of the dispersed phase (water) fluctuated. The durability test results regarding the modified surfaces show that the hydrophobicity of the modified COC surfaces could be sustained for up to four months, deteriorating with time thereafter. Our study can provide a potential solution useful in and guidance for the large-scale industrial production of droplet microfluidic devices for various applications, including polymerase chain reaction and single-cell analysis.

The predictive value of hematological inflammatory markers for acute kidney injury and mortality in adults with hemophagocytic Lymphohistiocytosis: A retrospective analysis of 585 patients.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological hyperactivation-related disease with a high mortality rate. The purpose of this study was to examine the relationship between complete blood count parameters and the occurrence of acute kidney injury (AKI) and mortality in patients with HLH. METHODS: We included 585 adult patients with HLH. Logistic regression models for AKI and 28-day mortality were developed. RESULTS: Multivariate logistic regression models revealed that hemoglobin (HB) ≤ 7.3 g/dl (adjusted OR, 1.651; 95% CI, 1.044-2.612), hemoglobin-to-red blood cell distribution width ratio (HRR) < 0.49 (adjusted OR, 1.692), neutrophil-to-lymphocyte ratio (NLR) ≥ 3.15 (adjusted OR, 1.697), and neutrophil-to-lymphocyte-platelet ratio (NLPR) ≥ 11.0 (adjusted OR, 1.608) were independent risk factors for the development of AKI. Moreover, lower platelet levels (31 × 109/L < platelets < 84 × 109/L, adjusted OR, 2.133; platelets ≤ 31 × 109/L, adjusted OR, 3.545) and higher red blood cell distribution width-to-platelet ratio (RPR) levels (0.20 < RPR < 0.54, adjusted OR, 2.595; RPR ≥ 0.54, adjusted OR, 4.307), lymphocytes ≤ 0.34 × 109/L (adjusted OR, 1.793), NLPR ≥ 11.0 (adjusted OR, 2.898), and the aggregate index of systemic inflammation (AISI) ≤ 7 (adjusted OR,1.778) were also independent risk factors for 28-day mortality. Furthermore, patients with AKI had a worse prognosis than those without AKI (P < 0.05). CONCLUSION: In patients with HLH, hematological parameters are of great value for the early identification of patients at high risk of AKI and 28-day mortality.

Preparation and Properties of Natural Polysaccharide-Based Drug Delivery Nanoparticles.

In recent years, natural polysaccharides have been widely used in the preparation of drug delivery systems. In this paper, novel polysaccharide-based nanoparticles were prepared by layer-by-layer assembly technology using silica as a template. The layers of nanoparticles were constructed based on the electrostatic interaction between a new pectin named NPGP and chitosan (CS). The targeting ability of nanoparticles was formed by grafting the RGD peptide, a tri-peptide motif containing arginine, glycine, and aspartic acid with high affinity to integrin receptors. The layer-by-layer assembly nanoparticles (RGD-(NPGP/CS)3NPGP) exhibited a high encapsulation efficiency (83.23 ± 6.12%), loading capacity (76.51 ± 1.24%), and pH-sensitive release property for doxorubicin. The RGD-(NPGP/CS)3NPGP nanoparticles showed better targeting to HCT-116 cells, the integrin αvß3 high expression human colonic epithelial tumor cell line with higher uptake efficiency than MCF7 cells, the human breast carcinoma cell line with normal integrin expression. In vitro antitumor activity tests showed that the doxorubicin-loaded nanoparticles could effectively inhibit the proliferation of the HCT-116 cells. In conclusion, RGD-(NPGP/CS)3NPGP nanoparticles have potential as novel anticancer drug carriers because of their good targeting and drug-carrying activity.

The anti-tumor efficiency of low-dose apatinib-based chemotherapy in pretreated HER2-negative breast cancer with brain metastases.

BACKGROUND: More than half of the metastatic breast cancer patients with brain metastases (BCBM) are HER-2 negative, and the prognosis of HER2-negative BCBM is dismal. But few clinical trials have investigated systemic therapies for this subgroup of patients. METHODS: This real-world study included 58 HER2-negative BCBMs who received low-dose apatinib (250 mg daily) in combination with chemotherapy between 18 March 2017 and 31 December 2021. The objective response rate (ORR) of the central nervous system, clinical benefit rate (CBR), progression-free survival of central nervous system (CNS-PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for CNS-PFS and OS. RESULTS: At the cut-off date, the median follow-up time was 28.2 months. Of the 58 patients, 36 patients were HR+/HER2-, and 22 patients were TNBC. The CNS-ORR was 17.2% (95%CI 9.6% to 28.9%) and the CBR was 53.4% (95%CI 40.8% to 65.7%). The median duration of CNS-PFS for the entire cohort was 6.4 months, and the median OS was 10.7 months. The median CNS-PFS and OS were not affected by hormone receptor status, disease-free survival, the number of prior lines of therapy and local treatment. The most common grade 2-3 adverse events associated with low-dose apatinib were hypertension (20.6%), elevated bilirubin (10.4%), hypothyroidism (10.3%), and hand-foot skin reaction (10.3%). CONCLUSION: Apatinib-based chemotherapy demonstrates potential feasibility with acceptable tolerance for HER2-negative BCBM. Its clinical application in BCBM still needs further verification.

HER2-negative breast cancer patients with brain metastases (BCBM) face an extremely poor prognosis, and a lack of effective treatment options. Apatinib, as a small molecule anti-angiogenic TKI, might have special central nervous system activity. Apatinib-based chemotherapy exhibits good tolerance and gains a favorable survival for HER2-negative BCBM.