Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.

OBJECTIVE: Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. METHODS: We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. RESULTS: In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). CONCLUSIONS: We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

BACKGROUND: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. METHODS: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. RESULTS: Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. CONCLUSIONS: Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

BACKGROUND: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. METHODS: Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. RESULTS: Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. CONCLUSIONS: Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

Resistance Monitoring of Nilaparvata lugens to Pymetrozine Based on Reproductive Behavior.

On the basis of the inhibition effects of pymetrozine on the reproductive behavior of N. lugens, we established a bioassay method to accurately evaluate the toxicity of pymetrozine in N. lugens and clarified the level of pymetrozine resistance of N. lugens in the field. In this study, pymetrozine's effects on the fecundity of N. lugens were evaluated using the topical application method and rice-seedling-dipping method. Moreover, the resistance of N. lugens to pymetrozine in a pymetrozine-resistant strain (Pym-R) and two field populations (YZ21 and QS21) was determined using the rice-seedling-dipping method and fecundity assay methods. The results showed that treatment of N. lugens third-instar nymphs with LC15, LC50, and LC85 doses of pymetrozine resulted in a significantly reduced fecundity of N. lugens. In addition, N. lugens adults treated with pymetrozine, using the rice-seedling-dipping and topical application method, also exhibited a significantly inhibited fecundity. Using the rice-stem-dipping method, pymetrozine resistance levels were shown to be high in Pym-R (194.6-fold), YZ21 (205.9-fold), and QS21 (212.8-fold), with LC50 values of 522.520 mg/L (Pym-R), 552.962 mg/L (YZ21), and 571.315 (QS21) mg/L. However, when using the rice-seedling-dipping or topical application fecundity assay method, Pym-R (EC50: 14.370 mg/L, RR = 12.4-fold; ED50: 0.560 ng/adult, RR = 10.8-fold), YZ21 (EC50: 12.890 mg/L, RR = 11.2-fold; ED50: 0.280 ng/adult; RR = 5.4-fold), and QS21 (EC50: 13.700 mg/L, RR = 11.9-fold) exhibited moderate or low levels of resistance to pymetrozine. Our studies show that pymetrozine can significantly inhibit the fecundity of N. lugens. The fecundity assay results showed that N. lugens only developed low to moderate levels of resistance to pymetrozine, indicating that pymetrozine can still achieve effective control on the next generation of N. lugens populations.

Anthraquinone metabolites isolated from the rhizosphere soil Streptomyces of Panax notoginseng (Burk.) F. H. Chen target MMP2 to inhibit cancer cell migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F. H. Chen belongs to the Araliaceae family. It has been used by traditional Chinese people in Northeast Asia for centuries as an antidiabetic, antioxidant, antitumor agent, etc. Endophytic or rhizospheric microorganisms play key roles in plant defense mechanisms, and they are essential in the discovery of pharmaceuticals and valuable new secondary metabolites. In particular, endophytic or rhizospheric microorganisms of traditional medicinal plants. AIM OF THE STUDY: To discover valuable new secondary metabolites from rhizosphere soil Streptomyces sp. SYP-A7185 of P. notoginseng, and to explore potential bioactivities and targets of metabolites protrusive function. MATERIALS AND METHODS: The metabolites were obtained via column chromatography and identified by multiple spectroscopic analyses. The antitumor, antioxidant, antibacterial, and antiglycosidases effects of isolated metabolites were tested using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetazolium bromide (MTT), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 96-well turbidimetric, and α-glucosidase inhibitory assays. The potential antitumor targets were predicted through network pharmacological approaches. The interactions between metabolites and target were verified by molecular docking and biolayer interferometry (BLI) assay. The effects of cancer cells migration were detected through wound healing assays in A549 and MCF-7. Other cellular validation experiments including reverse transcription-quantitative PCR (RT‒qPCR) and western blotting (WB) were used to confirm the hypothesis of network pharmacology. RESULTS: Five different chemotypes of anthraquinone derivatives (1-10), including six new compounds (3, 6-10), were identified from Streptomyces sp. SYP-A7185. Compounds 1-6 and 9 displayed moderate to strong cytotoxicity on five human cancer cell lines (A549, HepG2, MCF-7, MDA-MD-231, and MGC-803). Moreover, matrix metalloproteinase-2 (MMP2) were predicted as a potential antitumor target of metabolites 1-6 and 9 by comprehensive network pharmacology analysis. Later, BLI assays revealed strong intermolecular interactions between MMP2 and antitumor metabolites, and molecular docking results showed the interaction of metabolites 1-6 and 9 with MMP2 was dependent on the crucial amino acid residues of LEU-83, ALA-84, LEU-117, HIS-131, PRO-135, GLY-136, ALA-140, PRO-141, TYR-143, and THR-144. These results implied that metabolites (1-6 and 9) might inhibit cancer cell migration besides cancer cell proliferation. After that, the cell wound healing assay showed that the cell migration processes were also inhibited after the treatments of compounds 1 and 3 in A549 and MCF-7 cells. In addition, the RT‒qPCR and WB results demonstrated that the gene expression levels of MMP2 were decreased after the treatment with compounds 1 and 3 in A549 and MCF-7 cells. Besides, compound 2 displayed moderate antioxidant activity (EC50, 27.43 µM), compounds 3 and 6 exhibited moderate antibacterial activity, and compound 3 inhibited α-glucosidase with an IC50 value of 13.10 µM. CONCLUSIONS: Anthraquinone metabolites, from rhizosphere soil Streptomyces sp. of P. notoginseng, possess antitumor, antioxidant, antibacterial, and antiglycosidase activities. Moreover, metabolites 1 and 3 inhibit cancer cells migration through downregulating MMP2.

Serum irisin level is higher in peritoneal dialysis than in hemodialysis.

BACKGROUND: Previous studies have proved that irisin is related to the development of chronic kidney disease. In this study, we aimed to compare serum irisin level in patients treated with peritoneal dialysis (PD) and hemodialysis (HD). METHODS: Two hundred and fifty-two dialysis patients (146 PD patients and 106 HD patients) were included in the study. Levels of serum irisin and other parameters were compared between the two groups' patients. RESULTS: There were higher serum irisin levels in PD patients than those in HD patients [113.10 (106.15 ~ 119.15) ng/ml vs. 45.72(21.67 ~ 79.71) ng/ml, P < 0.001]. Moreover, body fat mass, percent body fat, serum calcium, high-density lipoprotein, low-density lipoprotein, carbon dioxide combining power (CO2CP) and residual renal function were higher in patients on PD than that in those on HD, whereas levels of lean body mass, systolic blood pressure, albumin, serum uric acid, potassium, and phosphorus（It should be "were" replace are) are higher in HD patients in comparison to PD patients. Dialysis modality (PD/HD), serum CO2CP level, lean body mass, and percent body fat independently positively correlated with natural logarithm of irisin (lnirisin) by multivariate linear regression analysis. CONCLUSIONS: In this study, we prove that serum irisin level is significantly higher in patients treated with peritoneal dialysis than that with hemodialysis. As well as, increasing skeletal muscle mass and fat body percent, and correcting metabolic acidosis may increase serum irisin levels.

Monitoring, cross-resistance, inheritance, and fitness costs of brown planthoppers, Nilaparvata lugens, resistance to pymetrozine in China.

BACKGROUND: The brown planthopper, Nilaparvata lugens, is considered the most destructive pest of rice in many Asian countries including China. Use of pymetrozine in insect resistance management (IRM) has been one strategy to control this pest. In this study, we reported the status of pymetrozine resistance in Nilaparvata lugens (Stål) collected from China over the period 2017-2021 and selected a strain of N. lugens resistant to pymetrozine and evaluated the cross-resistance, inheritance and fitness costs of the resistance. RESULTS: Monitoring data (2017-2021) showed that field populations of N. lugens in China developed moderate- to high-level pymetrozine resistance during these 5 years. By continuous selection with pymetrozine in the lab, the pymetrozine selected N. lugens strain (Pym-R98 ) developed a 225.2-fold resistance compared to a susceptible strain. The Pym-R98 strain showed high cross-resistance to dinotefuran (66.6-fold) and low cross-resistance to nitenpyram (5.2-fold) and sulfoxaflor (5.8-fold). Inheritance pattern analysis of Pym-R93 revealed that resistance to pymetrozine was polygenic, autosomal and incompletely dominant. Fitness costs of pymetrozine resistance were present in Pym-R90 and WA2020 strains with a relative fitness of 0.72 and 0.60, respectively. The developmental duration of Pym-R90 and WA2020 was significantly longer and hatchability was significantly lower compared to pymetrozine-susceptible strain (Pym-S). CONCLUSIONS: N. lugens has developed high level of resistance to pymetrozine. Pymetrozine-resistance brown planthopper had cross-resistance with some of neonicotinoids such as dinotefuran, nitenpyram and sulfoxaflor. The autosomal, incompletely dominant and polygenic resistance to pymetrozine in N. lugens and the fitness costs associated with this resistance can be exploited in IRM strategies to preserve the lifetime of pymetrozine for control of N. lugens in China. © 2022 Society of Chemical Industry.

Effects of nicotinic acetylcholine receptor subunit deletion mutants on insecticide susceptibility and fitness in Drosophila melanogaster.

BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) are major excitatory neurotransmitter receptors in insects and also the target site for many insecticides. Unfortunately, the effectiveness of these insecticides is diminishing as a consequence of the evolution of insecticide resistance. Further exploration of insecticide targets is important to sustainable pest management. RESULTS: In order to validate the role of nAChR subunits in insecticide susceptibility and test whether the subunit's absence imposes the fitness cost on insects, we determined the susceptibility of eight nAChR subunit deletion mutants of Drosophila melanogaster to nine insecticides. These findings highlighted the specific resistance of the Dα6 deletion mutant to spinosyns. Although triflumezopyrim, dinotefuran and imidacloprid are competitive modulators of nAChRs, differences in susceptibility of the insect with different deletion mutants suggested that the target sites of these three insecticides do not overlap completely. Mutants showed decreased susceptibility to insecticides, accompanied by a reduction in fitness. The number of eggs produced by Dα1attP , Dα2attP , Dß2attP and Dß3attP females was significantly lesser than that of the vas-Cas9 strain as the control. In addition, adults of Dα2attP , Dα3attP and Dα7attP strains showed lower climbing performance. Meanwhile, males of Dα3attP , Dα5attP , Dß2attP and Dß3attP , and females of Dß2attP showed significantly shorter longevity than those of the vas-Cas9 strain. CONCLUSION: This study provides new insights into the interactions of different insecticides with different nAChRs subunit in D. melanogaster as a research model, it could help better understand such interaction in agricultural pests whose genetic manipulations for toxicological research are often challenging. © 2022 Society of Chemical Industry.

Advances in Multi-Omics Study of Prognostic Biomarkers of Diffuse Large B-Cell Lymphoma.

As the most common subtype of non-Hodgkin's lymphoma, diffuse large B-cell lymphoma (DLBCL) is characterized by a huge degree of clinical and prognostic heterogeneity. Currently, there is an urgent need for highly specific and sensitive biomarkers to predict the therapeutic response of DLBCL and assess which patients can benefit from systemic chemotherapy to help develop more precise therapeutic regimens for DLBCL. Systems biology (holistic study of diseases) is more comprehensive in quantifying and identifying biomarkers, helps addressing major biological problems, and possesses high accuracy and sensitivity. In this article, we provide an overview of research advances in DLBCL prognostic biomarkers made using the multi-omics approach of genomics, transcriptomics, epigenetics, proteomics, metabonomics, radiomics, and the currently developing single-cell technologies.

Irisin alleviates vascular calcification by inhibiting VSMC osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling pathway in chronic kidney disease.

BACKGROUND AND AIMS: Vascular calcification (VC) is an intricate active process, significantly controlled by vascular smooth muscle cells (VSMCs). Mitochondrial dysfunction plays a pivotal role in VC and VSMCs osteoblastic transformation. We previously reported that decreased levels of Irisin were independently associated with VC in hemodialysis patients. The present study aimed to investigate the role of Irisin in VC, especially in VSMCs osteoblastic transformation and mitochondrial function. METHODS: In vitro, VSMCs calcification was induced by ß-glycerophosphate, while in vivo VC was triggered by adenine and high phosphorus diet. Alizarin red, Von Kossa staining, and calcium and Alp activity were performed to test VC. Western blot and immunohistochemical staining were employed to analyze the expression of proteins associated with VSMCs osteoblastic transformation and AMPK signaling. Mitochondrial membrane potential (MMP) and structures were observed by immunofluorescence staining. RESULTS: Irisin alleviated VSMCs calcification induced by ß-glycerophosphate. Mechanistically, Irisin activated AMPK and downregulated the expression of Drp1, further alleviating mitochondria fission and VSMCs osteoblastic transformation. In vivo, Irisin decreased serum creatinine, urea and phosphorous levels in chronic kidney disease (CKD) mice. Importantly, Irisin treatment postponed CKD-associated VC with the upregulation of α-Sma and p-AMPK expression, and the downregulation of Runx2 and Drp1 expression. CONCLUSIONS: Our results firstly reveal that Irisin inhibits CKD-associated VC. Irisin suppresses VSMCs osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling.

Overexpression of ATP-binding cassette transporter Mdr49-like confers resistance to imidacloprid in the field populations of brown planthopper, Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens (Stål), is the most severe pest attacking rice crops using sucking mouthparts. It causes significant damages to rice growth and food production worldwide. With the long-term and wide use of insecticides, field populations of BPH have developed resistance to many insecticides. RESULTS: Here, we showed that upregulation of an ATP-binding cassette transporter gene NlMdr49-like contributes to imidacloprid resistance in field populations of BPH. A comparative transcriptome analysis was performed to evaluate the gene expression in two field populations (JXSG18 and YNTC18). Compared with a susceptible strain (Sus), 202 upregulated genes and 170 downregulated genes were identified in both field populations. Functional enrichment analysis revealed that the differentially expressed genes (DEGs) are mainly linked to metabolic process and transmembrane transport. Among the candidate DEGs, NlMdr49-like was significantly upregulated in both field populations. Based on the genome and transcriptome of BPH, the full-length complementary DNA of NlMdr49-like was sequenced and its molecular characteristics were analyzed. Expression pattern analysis of various tissues showed that NlMdr49-like was predominantly expressed in midgut and Malpighian tubules which are important excretion organs. Knocking down NlMdr49-like reduced BPH resistance to imidacloprid, but did not affect its resistance to the other nine insecticides (chlorpyrifos, thiamethoxam, nitenpyram, dinotefuran, sulfoxaflor, triflumezopyrim, ethiprole, buprofezin and pymetrozine). Furthermore, a transgenic strain of Drosophila melanogaster overexpressing NlMdr49-like was less susceptible to imidacloprid. CONCLUSIONS: Our findings indicate that upregulation of NlMdr49-like is another mechanism contributing to imidacloprid resistance in N. lugens. This result is helpful to further understand the resistance mechanism of N. lugens to imidacloprid. © 2021 Society of Chemical Industry.

Tumor-associated macrophages: A promising target for a cancer immunotherapeutic strategy.

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application.

Lung cancer is the leading cause of cancer-related mortality worldwide. Tumorigenesis involves a multistep process resulting from the interactions of genetic, epigenetic, and environmental factors. Genome-wide association studies and sequencing studies have identified many epigenetic alterations associated with the development of lung cancer. Epigenetic mechanisms, mainly including DNA methylation, histone modification, and noncoding RNAs (ncRNAs), are heritable and reversible modifications that are involved in some important biological processes and affect cancer hallmarks. We summarize the major epigenetic modifications in lung cancer, focusing on DNA methylation and ncRNAs, their roles in tumorigenesis, and their effects on key signaling pathways. In addition, we describe the clinical application of epigenetic biomarkers in the early diagnosis, prognosis prediction, and oncotherapy of lung cancer. Understanding the epigenetic regulation mechanism of lung cancer can provide a new explanation for tumorigenesis and a new target for the precise treatment of lung cancer.

Effect of Bamboo Flour Grafted Lactide on the Interfacial Compatibility of Polylactic Acid/Bamboo Flour Composites.

Bamboo flour (BF) was grafted onto lactide (LA) in the molten state using stannous octoate as a catalyst to form BF-g-LA. Then, polylactic acid (PLA) was blended with BF (PLA/BF, 85/15 wt %) to prepare PLA/BF/BF-g-LA composites using BF-g-LA as a compatibilizer. The grafting rate of BF was characterized using infrared testing and elemental analysis. To investigate the effect of BF-g-LA on the performance of PLA/BF/BF-g-LA composites, the phase morphology, thermal stability, and mechanical properties of the composites were characterized using scanning electron microscopy, thermogravimetric analysis, and universal material testing, respectively. The addition of BF-g-LA improved the interface compatibility between PLA and BF. When the BF-g-LA content was 2 phr, the tensile and impact strengths of PLA/BF/BF-g-LA composites were 55.3 MPa and 9.56 kJ/m2, representing 30% and 27% increases, respectively, relative to corresponding values for PLA/BF composites.

Cardiac septic pulmonary embolism: A retrospective analysis of 20 cases in a Chinese population.

Based on the source of the embolus, septic pulmonary embolism (SPE) can be classified as cardiac, peripheral endogenous, or exogenous. Cardiac SPEs are the most common.We conducted a retrospective analysis of 20 patients with cardiac SPE hospitalized between 1991 and 2013 at a Chinese tertiary referral hospital.The study included 14 males and 6 females with a median age of 38.1 years. Fever (100%), cough (95%), hemoptysis (80%), pleuritic chest pain (80%), heart murmur (80%), and moist rales (75%) were common clinical manifestations. Most patients had a predisposing condition: congenital heart disease (8 patients) and an immunocompromised state (5 patients) were the most common. Staphylococcal (8 patients) and Streptococcal species (4 patients) were the most common causative pathogens. Parenchymal opacities, nodules, cavitations, and pleural effusions were the most common manifestations observed via computed tomography (CT). All patients exhibited significant abnormalities by echocardiography, including 15 patients with right-sided vegetations and 4 with double-sided vegetations. All patients received parenteral antimicrobial therapy as an initial treatment. Fourteen patients received cardiac surgery, and all survived.Among the 6 patients who did not undergo surgery, only 1 survived. Most patients in our cardiac SPE cohort had predisposing conditions. Although most exhibited typical clinical manifestations and radiography, they were nonspecific. For suspected cases of SPE, blood culture, echocardiography, and CT pulmonary angiography (CTPA) are important measures to confirm an early diagnosis. Vigorous early therapy, including appropriate antibiotic treatment and timely cardiac surgery to eradicate the infective source, is critical.

Whole Lung Lavage Treatment of Chinese Patients with Autoimmune Pulmonary Alveolar Proteinosis: A Retrospective Long-term Follow-up Study.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease, the most common type of which is autoimmune PAP. The gold standard therapy for PAP is whole lung lavage (WLL). Few studies have reported the optimal technique with which to evaluate the response to WLL. In this study, we aimed to identify parameters with which to assess the need for repeat WLL during a long-term 8-year follow-up. METHODS: We conducted a retrospective analysis of 120 patients with autoimmune PAP with 80 of whom underwent WLL. Physiologic, serologic, and radiologic features of the patients were analyzed during an 8-year follow-up after the first WLL treatment. RESULTS: Of the 40 patients without any intervention, 39 patients either achieved remission or remained stable and only one died of pulmonary infection. Of the 56 patients who underwent WLL for 1 time, 55 remained free from a second WLL and 1 patient died of cancer. Twenty-four required additional treatments after their first WLL. The baseline PaO 2 (P = 0.000), PA-aO 2 (P = 0.000), shunt fraction rate (P = 0.001), percent of predicted normal diffusing capacity of the lung for carbon monoxide (DLCO%Pred) (P = 0.016), 6-min walk test (P = 0.013), carcinoembryonic antigen (CEA) (P = 0.007), and neuron-specific enolase (NSE) (P = 0.003) showed significant differences among the three groups. The need for a second WLL was significantly associated with PaO 2 (P = 0.000), CEA (P = 0.050) , the 6-minute walk test (P = 0.026), and DLCO%Pred (P = 0.041). The DLCO%Pred on admission with a cut-off value of 42.1% (P = 0.001) may help to distinguish whether patients with PAP require a second WLL. CONCLUSIONS: WLL is the optimal treatment method for PAP and provides remarkable improvements for affected patients. The DLCO%Pred on admission with a cut-off value of 42.1% may distinguish whether patients with PAP require a second WLL.

Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease.

Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female predominance and presentation at younger age. Immunosuppressant therapy, lymphocytopenia, particularly low CD4+ T-lymphocyte counts, and low serum albumin levels may be disease susceptibility factors. Air-space opacities and nodules were the most common chest imaging features, and disseminated nocardiosis with lung and skin involvement was more common among them. Early diagnosis and anti-nocardial antibiotics with modulation of the basic immunosuppressive therapy were important for them.

Diagnostic and prognostic value of plasma adrenomedullin in COPD exacerbation.

BACKGROUND: Adrenomedullin (ADM) is a regulatory peptide with many biological actions, but little is known about its role in patients with COPD exacerbation. The purpose of this study was to evaluate the diagnostic and prognostic value of plasma ADM levels on hospital admission in patients with COPD exacerbation. METHODS: Consecutive subjects admitted to the hospital for COPD exacerbation were included and were followed up for 1 y; in addition, subjects with stable COPD from an out-patient clinic and healthy volunteers were recruited as controls. RESULTS: Compared with healthy subjects (145 pg/mL [interquartile range {IQR} 103-290 pg/mL]), plasma ADM levels were significantly higher in subjects with COPD exacerbation (270 pg/mL [IQR 170-510 pg/mL], P = .001) and in subjects with stable COPD (400 pg/mL [IQR 210-525 pg/mL], P < .001). In subjects with COPD exacerbation, ADM levels were significantly elevated during exacerbation (560 pg/mL [IQR 495-630 pg/mL]) compared with the recovery phase (470 pg/mL [IQR 393-553 pg/mL], P = .01) and the stable phase (200 pg/mL [IQR 143-308 pg/mL], P < .001). In receiver operating characteristic analysis, in subjects with COPD exacerbation, ADM had high diagnostic accuracy in differentiating between exacerbation and the stable phase (area under the curve 0.97, 95% CI 0.93-1.02, P < .001). In Cox regression analysis, plasma ADM was not independently associated with 1-y survival (P = .97), but it could accurately predicted the need for ICU care (hazard ratio 1.37, 95% CI 1.09-1.72, P = .008). CONCLUSIONS: Plasma ADM is a valuable biomarker to confirm COPD exacerbation; furthermore, plasma ADM independently predicts the need of ICU care, although it is not associated with long-term mortality in patients with COPD exacerbation.