Conformal Conversion of Polyphosphazene@Sb2MoO6 Nanowires to N/S-Doped/Carbon-Coated SbPO4/MoOx for High-performance Lithium Storage.

Alloy-type antimony (Sb) and conversion-type molybdenum (Mo) anodes have attracted extensive attention in the application of lithium-ion batteries (LIBs) owing to their high theoretical capacity. In this study, Sb2MoO6 nanowires are prepared via a hydrothermal method and assessed their thermal behavior upon heat treatment, observing an intriguing transformation from nanowire to Sb2O3/MoOx nanosheets. To enhance structure stability, the Sb2MoO6 nanowires are successfully coated with a polyphosphazene layer (referred to as PZS@Sb2MoO6), which not only preserved the nanowires form but also yielded N/S co-doped carbon-coated SbPO4/MoOx (NS-C@SbPO4/MoOx) nanowires following annealing in an inert environment. This composite benefits from the stable PO4 3- anion that serve as a buffer against volume expansion and form a Li3PO4 matrix during cycling, both of which substantially bolster ion transport and cycle endurance. Doping with heteroatoms introduces numerous oxygen vacancies, augmenting the number of electrochemically active sites, and carbon integration considerably enhances the electronic conductivity of the electrode and alleviates the volume-change-induced electrode pulverization. Employed as anode materials in LIBs, the NS-C@SbPO4/MoOx electrode exhibits remarkable cycling performance (449.8 mA h g-1 at 1000 mA g-1 over 700 cycles) along with superior rate capability (394.2 mA h g-1 at 2000 mA g-1).

Risk Factors for Contrast Media Extravasation in Intravenous Contrast-Enhanced Computed Tomography: An Observational Cohort Study.

RATIONALE AND OBJECTIVES: To identify the risk factors for contrast media (CM) extravasation and provide effective guidance for reducing its incidence. MATERIALS AND METHODS: We observed adult inpatients (n = 38 281) who underwent intravenous contrast-enhanced computed tomography between January 1, 2018, and December 31, 2022. Risk factors for CM extravasation were evaluated using univariate and multivariate logistic regression. RESULTS: Among the 38 281 inpatients who underwent enhanced computed tomography angiography, 3885 received peripherally inserted central venous catheters (PICCs) and 34 396 received peripheral short catheters. In 3885 cases of PICCs, no CM extravasation occurred, but in five cases, ordinary PICCs that are unable to withstand high pressure were mistakenly used; three of those patients experienced catheter rupture, and eventually, all five patients underwent unplanned extubation. Among 34 396 cases of peripheral short catheters, 224 (0.65%) had CM extravasation. Female sex (odds ratio [OR]=1.541, 95% confidence interval [CI]: 1.111-2.137), diabetes (OR=2.265, 95% CI: 1.549-3.314), venous thrombosis (OR=2.157, 95% CI: 1.039-4.478), multi-site angiography (OR=9.757, CI: 6.803-13.994), and injection rate ≥ 3 mL/s (OR=6.073, 95% CI: 4.349-8.481) were independent risk factors for CM extravasation. Due to peripheral vascular protection measures in patients with malignant tumor, there was a low incidence of CM extravasation (OR=0.394, 95% CI: 0.272-0.570). CONCLUSION: Main risk factors for CM extravasation are female, diabetes, venous thrombosis, multi-site angiography, and injection rate ≥ 3 mL/s. However, patients with malignant tumor have a low incidence of CM extravasation. CLINICAL IMPACT: Analysis of these risk factors can help reduce the incidence of CM extravasation.

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient.

Although ALK tyrosine kinase inhibitors (ALK-TKIs) have shown remarkable benefits in EML4-ALK positive NSCLC patients compared to conventional chemotherapy, the optimal sequence of ALK-TKIs treatment remains unclear due to the emergence of primary and acquired resistance and the lack of potential prognostic biomarkers. In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed responsiveness to brigatinib and ceritinib. Transcriptomic analysis revealed that brigatinib suppressed the activation of multiple inflammatory signaling pathways, potentially contributing to its anti-tumor activity. Moreover, we constructed a prognostic model based on the expression of IL6, CXCL1, and CXCL5, providing novel perspectives for predicting prognosis in EML4-ALK positive NSCLC patients. In summary, our results delineate clinical responses of sequential ALK-TKIs treatments and provide insights into the mechanisms underlying the superior effects of brigatinib in patients harboring ALKG1269A mutation and resistant towards alectinib, lorlatinib and crizotinib. The molecular signatures model based on the combination of IL6, CXCL1 and CXCL5 has the potential to predict prognosis of EML4-ALK positive NSCLC patients.

Sulfide-modified nanoscale zero-valent iron as a novel therapeutic remedy for septic myocardial injury.

INTRODUCTION: Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. OBJECTIVES: To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. METHODS: We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. RESULTS: The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. CONCLUSIONS: The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.

Antimicrobial, Antioxidant, and Anti-Inflammatory Nanoplatform for Effective Management of Infected Wounds.

Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.

Contrast media extravasation injury: a prospective observational cohort study.

OBJECTIVE: To identify the risk factors for moderate and severe contrast media extravasation and provide effective guidance to reduce the degree of extravasation injuries. METHODS: We observed 224 adult patients who underwent contrast media extravasation at Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province between January 1, 2018 and December 31, 2022. Risk factors for moderate extravasation injuries were evaluated using univariate and multivariate logistic regression. RESULTS: Among 224 patients, 0 (0%) had severe, 18 (8.0%) had moderate, and 206 (92.0%) had mild contrast media extravasation injury. Multivariate logistic regression analysis revealed malignant tumors (odds ratio [OR] = 6.992, 95% confidence interval [CI]: 1.674-29.208), Iohexol (OR = 9.343, 95% CI 1.280-68.214), large-volume (> 50 mL) extravasation (OR = 5.773, 95% CI 1.350‒24.695), and injection site (back of the hand) (OR = 13.491, 95% CI 3.056-59.560) as independent risk factors for moderate injury. CONCLUSION: Risk factors for moderate contrast media extravasation injury are malignant tumors, iohexol, large-volume (> 50 mL) extravasation, and back-of-the-hand injection. Analysis of these risk factors can help reduce the degree of injury after extravasation. CLINICAL RELEVANCE STATEMENT: High-risk patients with extravasation support should choose the appropriate contrast media type, avoiding back-of-the-hand injections. We recommend that patients with cancer be implanted with a high-pressure resistant central venous catheter and receive effective measures to timely detect and reduce extravasation.

An inflammation-associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma.

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.

Adherence to Analgesic Drugs and its Associated Factors among Patients with Cancer Pain: A Crosssectional Study in China.

Objectives: Pain is one of the most common and distressing symptoms co-occurring with cancer progression and treatment, and medication adherence plays an important role in achieving good pain control. However, research on medication adherence and influential factors among individuals with cancer pain (CP) is limited in China. The present study aimed to investigate the adherence to analgesics in patients with CP in China and to identify factors that may influence adherence. Methods: A cross-sectional study was conducted from June 2020 to February 2021. Study instruments consisted of a set of validated questionnaires, 5 measurement instruments including the numerical rating scale (NRS), ID-Pain, Morisky Medication Adherence Scale-Chinese validated version (MMAS-C), Beliefs about Medicines Questionnaire (BMQ) - Specific, and the Hospital Anxiety and Depression Scale (HADS). Results: A total of 141 participants with CP including 71 males (50.4%), aged 54.5±15.5 years were surveyed in this study. Overall, 83 patients (58.9%) showed adherence, but 58 patients (41.1%) showed non-adherence to analgesics. The univariate analysis showed that analgesic adherence was associated with pain duration of>3 months, outbreaks of pain in the last 24 hours, presence of side effects, getting analgesics in time, presence of neuropathic pain, stopping analgesics or adjusting dosage by themselves, presence of anxiety and depression, and beliefs about medicines. Moreover, the multivariate logistic regression showed that getting analgesic drugs in time (odds ratio [OR]=5.218, 95% confidence interval [CI] 1.691-16.100) and high BMQ-Necessity (OR=1.907, 95% CI 1.418-2.565) were associated with high adherence, stopping analgesics or adjusting dosage by themselves (OR=7.958, 95% CI 2.443-25.926) and high BMQ-Concern (OR=0.760, 95% CI 0.600-0.964) were more likely to be associated with non-adherence. Conclusion: In view of our findings, it may be critical for individuals to have a better understanding and strong beliefs about their prescribed analgesic drugs. Pain education, counseling and follow-up of patients and their caregivers, and removal of barriers to accessing analgesic drugs could be considered in further intervention strategies.

Protection of zero-valent iron nanoparticles against sepsis and septic heart failure.

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.

Percutaneous screw fixation assisted by hollow pedicle finder for superior pubic ramus fractures.

BACKGROUND: Pubic ramus fracture was an injury of anterior pelvic ring, the anterior pelvic ring plays an important role in maintaining the stability of the pelvis. The purpose of this study was to investigate the effect and indication of percutaneous retrograde pubic screw fixation assisted by hollow pedicle finder for pubic ramus fractures. METHODS: The clinical data of 68 patients with pubic ramus fracture treated with cannulated screw from March 2008 to March 2020 were retrospectively analyzed. According to the surgical methods, they were divided into traditional surgery group (32 cases in group A, with traditional retrograde pubic screw fixation) and modified surgery group (36 cases in group B, with percutaneous retrograde pubic screw fixation assisted by hollow open circuit device). Operation time, blood loss, incision length, screw length and complications were recorded and compared between the two groups. On the second day after surgery, the maximum fracture displacement over plain radiographs, entrance radiographs and exit radiographs of the pelvis was evaluated according to Matta criteria to evaluate the postoperative fracture reduction. Majeed score was used to evaluate the hip function at 12 months after surgery. RESULTS: The operations were successfully completed in both groups. The operation time, blood loss and incision length in group B were significantly less than those in group A (P < 0.05). There was no significant difference in screw length between the two groups (t = 0.797, P = 0.431). All patients were followed up for 8-38 months (mean 21.8 months). There were no vascular and nerve injury, fracture of internal fixator, screw entry into joint cavity, fracture nonunion and other complications in both groups. The fracture healing time of the two groups was 23.1 ± 2.1 weeks in group A while 22.7 ± 2.1 weeks in group B, respectively, and there was no statistical difference in the fracture healing time between the two groups (P > 0.05). In group A, there were 3 cases of incision infection, 1 case of incision fat liquefaction and 2 cases of lower extremity deep venous thrombosis, and the complication rate was 18.8%. There was only 1 case of lower extremity deep vein thrombosis in group B, and the complication rate was 2.8%, which was significantly lower than that in group A. The fracture in one case after surgery was found to be displaced in group A and no fracture was found in group B. There was no significant difference between the two groups in Matta imaging evaluation on the next day after surgery and Majeed function evaluation at 12 months after surgery (P > 0.05). CONCLUSION: Percutaneous retrograde pubic ramus screw fixation assisted by hollow pedicle finder is effective in the treatment of pelvic pubic ramus fracture. It has the advantages of less incision, shorter operation time, less blood loss and lower incidence of complications compared with traditional methods. However, correct surgical indications should be required when we apply this surgical method.

The novel STAT3 inhibitor WZ-2-033 causes regression of human triple-negative breast cancer and gastric cancer xenografts.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Anlotinib suppresses lung adenocarcinoma growth via inhibiting FASN-mediated lipid metabolism.

Background: Anlotinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, has been widely used in advanced lung cancer patients, but the intrinsic mechanism of cancer cell elimination is not fully disclosed. In this study, we reported that anlotinib suppressed lung adenocarcinoma (LUAD) growth through inhibiting fatty acid synthase (FASN)-mediated lipid metabolism. Methods: To investigate the underlying mechanisms of anlotinib, an A549 cell line-derived xenograft model was constructed and a proteomics technique was employed to screen potential markers. Gas chromatography-mass spectrometry (GC-MS) profiling of medium-long chain fatty acid and neutral lipid droplet fluorescence staining were employed to detect lipid metabolism in cancer cells. Subsequently, the effects of anlotinib on FASN expression were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Short hairpin RNA (shRNA) knockdown of FASN was used to assess the role of FASN in the antitumor effect of anlotinib. A patient-derived xenograft (PDX) model was established to validate the efficacy of anlotinib in the patient and IHC staining of FASN was examined. Results: Our data revealed that anlotinib significantly decreased the expression of proteins related to lipid metabolism. GC-MS profiling of medium-long chain fatty acid and neutral lipid droplet fluorescence staining validated that anlotinib could disturb the fatty acid metabolism in cancer cells, especially de novo lipogenesis. Mechanically, the messenger RNA (mRNA) and protein of FASN were down-regulated by anlotinib in A549 cells and FASN knockdown could diminish the antitumor effect of anlotinib in vitro. Remarkable tumor shrinkage by anlotinib was further shown in a patient with multiple-line treatment failure, and FASN reduction was evidenced in the corresponding patient-derived xenograft (PDX) model. Conclusions: Anlotinib could inhibit the growth of LUAD through FASN-mediated lipid metabolism. Our findings provide new insights into the antitumor mechanism of anlotinib in lung adenocarcinoma.

[Study on effect of gypenosides on insulin sensitivity of rats with diabetes mellitus via regulating NF-κB signaling pathway].

This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase ß(p-IKKß), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1ß and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKß, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKß, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.

Pemetrexed-Platinum With or Without Bevacizumab for Chinese Chemo-Naive Advanced Lung Adenocarcinoma Patients: A Real-World Study.

Despite recent advances in the treatment of advanced non-small-cell lung cancer (NSCLC), bevacizumab plus platinum-based doublet chemotherapy remains a commonly used first-line regimen. This study was conducted to compare the efficacy and safety of pemetrexed-platinum with or without bevacizumab in Chinese chemo-naive advanced lung adenocarcinoma patients in a real-world setting. We retrospectively collected 100 patients who received pemetrexed-platinum with or without bevacizumab (PP, n = 46; Bev+PP, n = 54) until disease progression or unacceptable toxicity. Clinical characteristics of patients were balanced, except for the proportion of stage IV b+c (Bev+PP and PP: 67.4 vs. 37.0%, p = 0.0066). Bev+PP significantly improved the objective response rate (ORR, 65 vs. 30%, p = 0.0004) and progression-free survival (PFS, 7.4 vs. 6.8 months, p = 0.009), but not overall survival (OS, 17.5 vs. 15.0 months, p = 0.553) compared with PP. Treatment (p = 0.001), gender (p = 0.008), adrenal metastasis (p = 0.001), and liver metastasis (p = 0.013) were independent risk factors for PFS. Patients with adrenal metastasis tended to be at the highest risk of not benefiting from bevacizumab addition (HR [95% CI]: 2.244 [0.6495-7.753]). The safety profile was acceptable, and grade ≥3 toxicity occurred similarly. This study showed that pemetrexed-platinum plus bevacizumab was effective compared to chemotherapy alone in Chinese patients with advanced NSCLC.

Fabrication of antigen-containing nanoparticles using microfluidics with Tesla structure.

The polyethyleneimine (PEI)-based antigen delivery system has been proved valuable for therapeutic vaccines. However, the previous bulk mixing method is not ideal to prepare PEI-base antigen- containing nanoparticles. The wide-size distribution and poor reproducibility limit its further application. In this research, we developed a microfluidic method to prepare nanopolyplexes on chips with Tesla structure to improve the fabrication. The structure and bioactivity of protein were not hampered by the shearing force in microfluidics. Comparison between physiochemical parameters suggested that the polyplexes prepared by Tesla chips were more uniform than those prepared by bulk mixing and non-Tesla chips. The reproducibility was improved obviously. The preparation was not influence much by the operating parameters such as flow rates, reagents concentration, and switching of inlets. The results indicated that it was a robust and reliable method. The data that were obtained from BMDC model demonstrated that the nanopolyplexes with optimal weight ratio had higher antigen cross-presentation efficiency than those in free antigen group. In conclusion, Tesla structured microfluidics offers a better method over bulk mixing in the preparation of PEI-based antigen-containing nanopolyplexes. It greatly expands the scope of our study and increases the potential of PEI-based antigen delivery system.

Crack Healing and Mechanical Properties Recovery in SA 508⁻3 Steel.

Internal cracks could be healed under the process of hot plastic deformation. In this study, mechanical properties recovery after crack healing in SA 508⁻3 steel were investigated. Microstructures of the crack healing zones were observed using an optical microscope (OM) and electron back scattered diffraction (EBSD) technology, and the recovery degrees of mechanical properties in the crack healing zones with the healing temperature and a reduction ratio were tested systematically. The results showed that the internal cracks in SA 508⁻3 steel disappeared and were replaced by newly formed grains, achieved by recrystallization and abnormal grain growth. The tensile properties of crack healing zones could be fully restored, while their impact and low cycle fatigue properties could only be partially achieved. The recovery degrees of mechanical properties in crack healing zones increased with increasing the healing temperature and reduction ratio in the temperature range of 950⁻1050 °C. When the temperature was above 1150 °C, the impact properties began to deteriorate because of grain coarsening and larger MA (martensite⁻austenite) constituents. The microstructural evolution of the crack zone in the SA 508⁻3 steel was sketched.

Bioaccumulation and cycling of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in three mangrove reserves of south China.

Total 22 organochlorine pesticides (OCPs) compounds and 31 polychlorinated biphenyls (PCBs) congeners in mangrove sediments and tissues (leaf, branch, root and fruit) of nine species from three Mangrove Reserves of China were studied. The mean concentrations of total DDTs, HCHs, OCPs and PCBs in sediments were 2.84, 0.06, 3.84 and 0.17 ng g-1 dw, while those in tissues were 1.85, 0.22, 9.43 and 1.61 ng g-1 dw, respectively. The elevated OCPs and PCBs levels in mangrove leaves may be caused by atmospheric sedimentation. The biota sediment accumulation factor (BSAF) values of both OCPs (mean: 3.4) and PCBs (mean: 9.9) are generally larger than one, implying mangroves' bioaccumulation and their ability to intercept pollutants. The BSAFs of PCBs in mangrove tissues were negatively correlated with the PCB congener's octanol-water partition coefficients (KOW, R = 0.58, n = 31, p < 0.001), suggesting that lower chlorinated CB congeners are more bioaccumulative in mangroves. In order to better understanding the fate of these organochlorine compounds, the cycling (including the standing accumulation, the annual absorption, the annual net retention, the annual return, and the turnover period) of OCPs and PCBs in the Mangrove Reserves were estimated, and the results indicated that mangroves are playing important roles in retaining OCPs and PCBs.

Prognostic value of C-reactive protein/albumin ratio in predicting overall survival of Chinese cervical cancer patients overall survival: comparison among various inflammation based factors.

Background: Many studies have shown the prognostic value of inflammation based factors in different cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin (CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors, such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and squamous cell carcinoma antigen (SCC-Ag). Methods: This study was a retrospective analysis of the data related to 229 patients with newly diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by Chi-Square or Fisher's exact test. Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR = 2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone. Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition, NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation was present among SCC-Ag, NLR and CRP/Alb ratio. Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common histological SCC subtypes.

Immunization with alkyl hydroperoxide reductase subunit C reduces Fusobacterium nucleatum load in the intestinal tract.

Fusobacterium nucleatum (Fn) is an important tumour-associated bacterium in colorectal cancer (CRC). The antioxidant protein alkyl hydroperoxide reductase subunit C (AhpC) can induce strong antibacterial immune response during various pathogen infections. Our study aimed to evaluate the efficacy of Fn-AhpC as a candidate vaccine. In this work, by western blot analysis, we showed that Fn-AhpC recombinant protein could be recognized specifically by antibodies present in the sera of CRC patients; using the mouse Fn-infection model, we observed that systemic prophylactic immunization with AhpC/alum conferred significant protection against infection in 77.3% of mice. In addition, we measured the anti-AhpC antibody level in the sera of CRC patients and found that there was no obvious increase of anti-AhpC antibodies in the early-stage CRC group. Furthermore, we treated Fn with the sera from both immunized mice and CRC patients and found that sera with high anti-AhpC antibodies titre could inhibit Fn growth. In conclusion, our findings support the use of AhpC as a potential vaccine candidate against inhabitation or infection of Fn in the intestinal tract, which could provide a practical strategy for the prevention of CRC associated with Fn infection.