[Effect analysis of trimethylamine N-oxide and its precursors on susceptibility to pancreatic diseases].

OBJECTIVE: To investigate the causal relationship between trimethylamine N-oxide (TMAO) and its precursors (betaine, carnitine, and choline) and pancreatic diseases based on the Mendelian randomization (MR) method. METHODS: Genome-wide association study data of TMAO, betaine, carnitine, choline, acute pancreatitis (AP), chronic pancreatitis (CP), pancreatic cancer (PC), and circulating immune cell characteristics (white blood cell, lymphocyte, monocyte, neutrophil, eosinophil and basophil) were collected. According to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines, the available genetic variants [single nucleotide polymorphism (SNP)] were strictly screened. The causal relationship between exposure (TMAO and its precursors) and outcomes (pancreatic diseases and circulating immune cell characteristics) was evaluated using inverse variance weighting (IVW), MR-Egger regression and weighted median. The reliability of the results was evaluated by sensitivity analysis based on MR-Egger regression, MR-PRESSO, Cochrane's Q test and leave-one-out method. RESULTS: A total of 36 SNP associated with TMAO and its precursors were included. Five of these were associated with TMAO, 13 with betaine, 12 with carnitine, and 6 with choline. (1) MR analysis showed that TMAO may increase the risk of AP [odds ratio (OR) = 1.100, 95% confidence interval (95%CI) was 1.008-1.200, P = 0.032], and choline may reduce the risk of alcoholic acute pancreatitis (AAP; OR = 0.743, 95%CI was 0.585-0.944, P = 0.015). The analysis results of MR-Egger regression and weighted median were consistent with the IVW results. There is no evidence to support a causal relationship between TMAO and its precursors and the risk of CP and PC. Sensitivity analysis indicated that SNP analyzed by MR showed no heterogeneity and low pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. (2) There was a positive causal relationship between plasma TMAO level and circulating monocyte count (OR = 1.017, 95%CI was 1.000*-1.034, P = 0.048, * represented that the data was obtained by correcting to 3 decimal places from 1.000 1). The causal effect obtained by MR-Egger regression and weighted median analysis was consistent with the results of IVW. Sensitivity analysis illustrated SNP analyzed by MR showed no heterogeneity and pleiotropy. The leave-one-out method analysis determined that after excluding any SNP, the effect intervals of the remaining SNP on the results were similar to the overall effect intervals, which suggested the robustness of MR results. CONCLUSIONS: TMAO and choline may change the risk of AP, and TMAO may contribute to the increase of circulating monocyte count in AP.

Hepatoprotective effects of magnolol in fatty liver hemorrhagic syndrome hens through shaping gut microbiota and tryptophan metabolic profile.

BACKGROUND: Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks. RESULTS: Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites. CONCLUSIONS: Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.

Pharmacokinetics of trastuzumab and its efficacy and safety in HER2-positive cancer patients.

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients.

Systematic review of the efficacy and safety of lenvatinib in various solid tumors.

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. METHOD: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. RESULTS: A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. CONCLUSIONS: Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.

Prospects and challenges of CAR-T cell therapy combined with ICIs.

Immune checkpoint molecules are a group of molecules expressed on the surface of immune cells that primarily regulate their immune homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology that realizes tumor-targeted killing by constructing synthetic T cells expressing specific antigens through biotechnology. Currently, CAR-T cell therapy has achieved good efficacy in non-solid tumors, but its treatment of solid tumors has not yielded the desired results. Immune checkpoint inhibitors (ICIs) combined with CAR-T cell therapy is a novel combination therapy with high expectations to defeat solid tumors. This review addresses the challenges and expectations of this combination therapy in the treatment of solid tumors.

Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer.

BACKGROUND: Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear. METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration. RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05). CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.

Discovery and bioassay of disubstituted ß-elemene-NO donor conjugates: synergistic enhancement in the treatment of leukemia.

Natural products are essential sources of antitumor drugs. One such molecule, ß-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor ß-elemene derivatives were designed, with ß-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.

Mammalian trans-editing factor ProX is able to deacylate tRNAThr mischarged with alanine.

The precise coupling of tRNAs with their cognate amino acids, known as tRNA aminoacylation, is a stringently regulated process that governs translation fidelity. To ensure fidelity, organisms deploy multiple layers of editing mechanisms to correct mischarged tRNAs. Prior investigations have unveiled the propensity of eukaryotic AlaRS to erroneously attach alanine onto tRNACys and tRNAThr featuring the G4:U69 base pair. In light of this, and given ProXp-ala's capacity in deacylating Ala-tRNAPro, we embarked on exploring whether this trans-editing factor could extend its corrective function to encompass these mischarged tRNAs. Our in vitro deacylation assays demonstrate that murine ProXp-ala (mProXp-ala) is able to efficiently hydrolyze Ala-tRNAThr, while Ala-tRNACys remains unaffected. Subsequently, we determined the first structure of eukaryotic ProXp-ala, revealing a dynamic helix α2 involved in substrate binding. By integrating molecular dynamics simulations and biochemical assays, we pinpointed the pivotal interactions between mProXp-ala and Ala-tRNA, wherein the basic regions of mProXp-ala as well as the C3-G70 plays essential role in recognition. These observations collectively provide a cogent rationale for mProXp-ala's deacylation proficiency against Ala-tRNAThr. Our findings offer valuable insights into the translation quality control within higher eukaryotic organisms, where the fidelity of translation is safeguarded by the multi-functionality of extensively documented proteins.

A lightweight neural network for lung nodule detection based on improved ghost module.

Background: Computer tomography images are the preferred method of preoperative evaluation for lung disease. However, it remains difficult to detect and recognize nodules accurately and efficiently due to poor data imaging quality, heavy reliance on physician experience and the need for more human-computer interaction for diagnosis. Currently, image nodule detection based on deep convolutional neural networks has gained much momentum. Methods: To alleviate doctors' tremendous labor in the diagnosis procedure, and improve the accuracy of intelligent detection of lung nodules, we improved GhostNet and proposed a lightweight neural network for object detection for lung nodule image detection. Firstly, the bneck structure in the backbone feature extraction network is adopted and improved from the structure of MobileNetV3. The weights are adjusted by changing the initial channel attention mechanism and introducing a spatial-temporal attention mechanism. Then, in the enhanced feature extraction part, we mainly use depth-separable convolution blocks to replace the 3×3 convolution of the original network for the purpose of reducing the model parameters, and make more improvements based on the network structure to enhance the applicability of the network. Diagnostic precision, recall, F1-score, mAP and parameter count were calculated. Results: According to our lightweight neural network, F1-score, precision, and recall were 0.87, 86.34%, and 86.69%, respectively. Based on our dataset, the Yolov4-GNet network proposed in this research outperforms the current neural networks on both precision and recall as well as F1. Conclusions: The lung nodule detection method proposed in this research not only simplifies the processing of images, but also outperforms comparable methods in nodule detection rate and positioning accuracy, providing a new way for lung nodule detection.

Combination of chemotherapy and gaseous signaling molecular therapy: Novel ß-elemene nitric oxide donor derivatives against leukemia.

This study aimed to design and synthesize active hybrids of ß-elemene and nitric oxide (NO) donor pharmacophore as potential agents for treating leukemia. Derivatives reported herein exerted better inhibitory effects against human chronic myeloid leukemia K562 cells compared to ß-elemene (IC50 > 100 µM). The most potent compound 18f showed an IC50 value of 0.53 µM against K562 cells, as well as a high NO release level in vitro. In the K562 xenograft tumor mice model, compound 18f effectively inhibited the growth of the tumor, with a significant inhibition rate of 73.18%. After treatment with compound 18f, the body weight of mice did not decrease, indicating that it possessed good safety profile. All these proved that compound 18f was an excellent potential agent against leukemia.

Evaluation of HER-2 positive breast cancer treated with dual-targeted treatment of trastuzumab plus pertuzumab.

Objective: Clinical studies have shown that trastuzumab combined with pertuzumab (dual-targeted drug therapy) can significantly improve the treatment status and prognosis of HER-2 positive breast cancer patients through double targeting of HER-2. This study systematically evaluated the efficacy and safety of trastuzumab combined with pertuzumab in the treatment of HER-2 positive breast cancer.Method: We search relevant databases and collect RCTs on the treatment of HER-2 positive breast cancer with dual-targeted treatment. Meta-analysis was performed using Revman5.4 software.Results: A total of 10 studies for 8553 patients were included. Meta-analysis showed that, in terms of efficacy, overall survival (OS) (HR = 1.40, 95%CI = 1.29-1.53, p < 0.00001) and progression-free survival (PFS) (HR = 1.36, 95%CI = 1.28-1.46, p < 0.00001) in dual-targeted drug therapy were better than which in the single-targeted drug group. In terms of safety, the highest incidence (Relative risk, RR) of Adverse reactions was Infections and infestations (RR = 1.48, 95%CI = 1.24-1.77, p < 0.0001) follow by Nervous system disorders (RR = 1.29, 95%CI = 1.12-1.50, p = 0.0006), Gastrointestinal disorders (RR = 1.25, 95%CI = 1.18-1.32, p < 0.0001), Respiratory, thoracic, and mediastinal disorders (RR = 1.21, 95%CI = 1.01-1.46, p = 0.04), Skin and subcutaneous tissue disorders (RR = 1.14, 95%CI = 1.06-1.22, p = 0.0002) and General disorders (RR = 1.14, 95%CI = 1.04-1.25, p = 0.004) in dual-targeted drug therapy group. The incidence of Blood system disorder (RR = 0.94, 95%CI = 0.84-1.06, p = 0.32) and Liver dysfunction (RR = 0.80, 95%CI = 0.66-0.98, p = 0.03) was lower than that of the single targeted drug group.Conclusion: Dual-targeted treatment for HER-2-positive breast cancer can prolong the OS, PFS and improve the quality of patients' life. Meanwhile, it also brings a higher medication risk, which requires a rational selection of drug symptomatic interventions.

Biomarkers of related driver genes predict anti-tumor efficacy of immune checkpoint inhibitors.

Cancer is a disease with high morbidity and mortality in the world. In the past, the main treatment methods for cancer patients were surgery, radiotherapy and chemotherapy. However, with early treatment, the recurrence rate of cancer is higher, and the drug resistance of cancer cells is faster. In recent years, with the discovery of immune escape mechanism of cancer cells, Immunotherapy, especially Immune Checkpoint Inhibitors (ICIs), has made a breakthrough in the treatment of solid tumors, significantly prolonging the overall survival time and disease-free progression in some solid tumors, and its clinical benefits are more prominent than those of traditional anti-tumor drugs, which has become the hope of cancer patients after the failure of multi-line therapy. More and more studies have shown that there is a correlation between cancer driving genes and the clinical benefits of ICIs treatment, and the therapeutic effects and adverse reactions of ICIs can be predicted by the status of driving genes. Therefore, screening potential biomarkers of people who may benefit from immunotherapy in order to maximize the therapeutic benefits is a top priority. This review systematically summarizes the cancer driving genes that may affect the clinical benefits of immune checkpoint inhibitors, and provides accurate scientific basis for clinical practice.

Heavy metals in road dust across China: occurrence, sources and health risk assessment.

We investigated the occurrence of Cd, Cr, Cu, Ni, Pb and Zn in 28 road dust samples collected across China from June to August, 2020. The mean concentrations of Cd, Cr, Cu, Ni, Pb and Zn were 3.16, 24.2, 27.4, 10.4, 49.8 and 608 mg·kg- 1, respectively. The mean levels of Cd and Zn exceeded the Chinese background values by 32.6- and 8.2- fold. Cd, Ni mainly distributed in southern China, whereas Cu, Pb and Zn mainly distributed in central China. Higher concentrations of Cd, Cr, Cu and Pb were found in road dusts from urban areas than those from rural areas. Cu and Ni mainly came from natural sources; Pb and Cd mainly originated from industrial emissions and vehicle exhaust. Hand-mouth ingestion was the most common exposure pathway for both adults and children, followed by dermal contact and inhalation. Pb was found to be the highest risk element via ingestion. No significant non-carcinogenic risks and carcinogenic risks were found for local residents.

Second generation ß-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma.

Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, ß-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour efficacy. To improve the anti-tumour activity of ß-elemene, based on its minor molecular weight character, we introduced furoxan nitric oxide (NO) donors into the ß-elemene structure and designed six series of new generation ß-elemene NO donor hybrids. The synthesised compounds could effectively release NO in vitro, displayed significant anti-proliferative effects on U87MG, NCI-H520, and SW620 cell lines. In the orthotopic glioma model, compound Id significantly and continuously suppressed the growth of gliomas in nude mice, and the brain glioma of the treatment group was markedly inhibited (>90%). In short, the structural fusion design of NO donor and ß-elemene is a feasible strategy to improve the in vivo anti-tumour activity of ß-elemene.

Pharmacologic and genetic inhibition of cholesterol esterification enzymes reduces tumour burden: A systematic review and meta-analysis of preclinical models.

Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.

PD-L1 Acts as a Promising Immune Marker to Predict the Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

BACKGROUND: Programmed death ligand 1 (PD-L1) is a negative immune stimulatory molecule that plays a key role in tumor immune escape. We analyzed the clinical value of PD-L1-positive expression in predicting the outcome of breast cancer patients and to establish its role as new biomarker to guide precise treatment. PATIENTS AND METHODS: PubMed and Embase were searched for all original English-language articles published before January 30, 2019; all articles reported the predictive and prognostic implications of PD-L1+ in breast cancer. Data were analyzed by Stata SE 12 software. RESULTS: The PD-L1+ rate varied from 19.7% to 77.6% in breast cancer patients. Specifically, patients with estrogen receptor-positive, progesterone receptor-positive, luminal A, luminal B, and HER2+ disease subtypes had lower PD-L1 expression, while the PD-L1+ percentages did not follow any trend in patients with Ki-67+, normal-like, HER2 overexpression, and basal-like subtype. In addition, PD-L1+ was observed to be associated with significantly improved pathologic complete response to neoadjuvant chemotherapy (odds ratio = 2.01; 95% confidence interval, 1.35-3.01; P < .05). Using PD-L1+ to predict pathologic response showed obvious accuracy. However, PD-L1+ did not show significant association with risk of higher recurrence or metastasis, or higher death risk (hazard ratio = 0.91, P = .655; hazard ratio = 1.00, P = .995). CONCLUSION: PD-L1+ is a promising immune parameter with the potential to predict response to neoadjuvant chemotherapy, but it cannot indicate a higher risk of death, recurrence, or metastasis.

Sandwich-Type Nitrogen and Sulfur Codoped Graphene-Backboned Porous Carbon Coated Separator for High Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have been identified as the greatest potential next- generation energy-storage systems because of the large theoretical energy density of 2600 Wh kg-1. However, its practical application on a massive scale is impeded by severe capacity loss resulted from the notorious polysulfides shuttle. Here, we first present a novel technique to synthesize sandwich-type nitrogen and sulfur codoped graphene-backboned porous carbon (NSGPC) to modify the commercial polypropylene separator in Li-S batteries. The as-synthesized NSGPC exhibits a unique micro/mesoporous carbon framework, large specific surface area (2439.0 m² g-1), high pore volume (1.78 cm³ g-1), good conductivity, and in situ nitrogen (1.86 at %) and sulfur (5.26 at %) co-doping. Benefiting from the particular physical properties and chemical components of NSGPC, the resultant NSGPC-coated separator not only can facilitate rapid Li⁺ ions and electrons transfer, but also can restrict the dissolution of polysulfides to alleviate the shuttle effect by combining the physical absorption and strong chemical adsorption. As a result, Li-S batteries with NSGPC-coated separator exhibit high initial reversible capacity (1208.6 mAh g-1 at 0.2 C), excellent rate capability (596.6 mAh g-1 at 5 C), and superior cycling stability (over 500 cycles at 2 C with 0.074% capacity decay each cycle). Propelling our easy-designed pure sulfur cathode to a extremely increased mass loading of 3.4 mg cm-2 (70 wt. % sulfur), the Li-S batteries with this functional composite separator exhibit a superior high initial capacity of 1171.7 mAh g-1, which is quite beneficial to commercialized applications.

VEGFR-2 as a novel predictor of survival in gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Expression of VEGFRs may affect cancer prognosis. The aim of this work is to evaluate the prognostic significance of VEGFRs of patients with gastric cancer. METHODS: The databases PubMed, Embase, Web of Science, and Cochrane Library as well as ASCO and ESMO were searched systematically for articles reporting the prognostic significance of tissue VEGFRs in gastric cancer. The statistical analyses were carried out using Stata version 12.0. RESULTS: A total of 8 articles comprising 950 patients were eligible for meta-analysis. The combined HR of studies evaluating total VEGFRs overexpression was 1.42 (95% CI 1.01-2.00, P = 0.044), suggesting that it had prognosis significance in overall survival of gastric cancer. Subgroup analysis showed that it was VEGFR-2 (HR 1.81, 95% CI 1.31-2.49, P < 0.001) but not VEGFR-3 (HR 0.91, 95% CI 0.45-1.82, P = 0.787) overexpression was associated with an increased risk of median overall survival (mOS) and it can be a potentially predictive biomarker for gastric cancer. CONCLUSIONS: VEGFR-2 overexpression is a promising negative prognosis predictor for patients with gastric cancer. The prognosis significance of VEGFR-3 still need further study.

Metastases of transverse colon cancer to bilateral ovaries (Krukenberg tumor) and the left breast: A case report.

Breast cancer has the highest rate of incidence among all types of cancer in women. Only ~0.43% of breast malignancies occur as a result of metastatic lesions from extramammary tumors. The present study reports an extremely rare case of transverse colon cancer metastasizing to the bilateral ovaries and the left breast. The patient was a 47-year old female, who had a lump in the left breast without axillary lymphadenopathy. Specimens obtained by core needle biopsy were submitted for hematoxylin and eosin examination, and results revealed that the lump was a poorly differentiated adenocarcinoma. Since the patient had elevated levels of the carcinoembryonic antigen and a medical history of a Krukenberg tumor metastasized from colon cancer, immunohistochemical examinations were applied. Results identified that caudal-related homeobox protein 2 and cytokeratin 20 were positively stained, whilst cytokeratin 7 was negatively stained. Therefore, this patient was diagnosed as having colon cancer that had metastasized to the bilateral ovaries and the left breast. As the life expectancy of patients with cancer is increasing, types of metastases that used to be seen as rare are increasingly becoming more common. For clinicians, diagnosis should be cautious, and differential diagnosis should always be kept in mind.