FGTN: Fragment-based graph transformer network for predicting reproductive toxicity.

Reproductive toxicity is one of the important issues in chemical safety. Traditional laboratory testing methods are costly and time-consuming with raised ethical issues. Only a few in silico models have been reported to predict human reproductive toxicity, but none of them make full use of the topological information of compounds. In addition, most existing atom-based graph neural network methods focus on attributing model predictions to individual nodes or edges rather than chemically meaningful fragments or substructures. In current studies, we develop a novel fragment-based graph transformer network (FGTN) approach to generate the QSAR model of human reproductive toxicity by considering internal topological structure information of compounds. In the FGTN model, the compound is represented by a graph architecture using fragments to be nodes and bonds linking two fragments to be edges. A super molecule-level node is further proposed to connect all fragment nodes by undirected edges, obtaining global molecular features from fragment embeddings. The FGTN model achieved an accuracy (ACC) of 0.861 and an area under the receiver operating characteristic curve (AUC) value of 0.914 on nonredundant blind tests, outperforming traditional fingerprint-based machine learning models and atom-based GCN model. The FGTN model can attribute toxic predictions to fragments, generating specific structural alerts for the positive compound. Moreover, FGTN may also have the capability to distinguish various chemical isomers. We believe that FGTN can be used as a reliable and effective tool for human reproductive toxicity prediction in contribution to the advancement of chemical safety assessment.

[Correlation of anti-C1q antibodies with active systemic lupus erythematosus and lupus nephritis in children]. / 抗C1qæŠ—ä½“ä¸Žå„¿ç«¥æ´»åŠ¨æ€§ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®å’Œæ´»åŠ¨æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

Synthesis of 2,3-Fused Quinazolinones via the Radical Cascade Pathway and Reaction Mechanistic Studies by DFT Calculations.

An efficient radical cascade cyclization of unactivated alkenes toward the synthesis of a series of ring-fused quinazolinones has been developed in moderate to excellent yields using commercially available ethers, alkanes, and alcohols, respectively, under a base-free condition in a short time without a transition metal as catalyst. Notably, the transformations can be carried out with the advantages of a broad substrate scope and high atomic economy. Density functional theory calculations and wavefunction analyses were performed to elucidate the radical reaction mechanism.

The Geriatric Nutritional Risk Index as a Prognostic Factor in Patients with Advanced Non-Small-Cell Lung Cancer.

The Geriatric Nutritional Risk Index (GNRI) is widely applied as a prognostic factor in different cancers. We aimed to analyze the prognostic value of the GNRI in 257 patients diagnosed with advanced non-small-cell lung cancer (NSCLC). Patients with GNRI >98, 92-98, and <92 were grouped into normal, low risk and moderate/high risk groups, respectively. There were 45.1% patients at risk for malnutrition. Kaplan-Meier survival curves indicated that patients with lower GNRI scores had a poorer overall survival (OS). Two-year OS for normal, low risk and moderate/high risk groups were 57.4%, 42.3% and 15.8%, respectively. In multivariate survival analysis, GNRI (<92), body mass index (BMI, ≥24 kg/m2), combined therapy, hemoglobin and neutrophil-to-lymphocyte ratio (NLR) were independent prognostic factors of OS. Stratifying by age groups, GNRI (<92), hemoglobin and NLR were independent prognostic factors of OS in patients aged <65 years. GNRI (<92), smoking, BMI (≥24 kg/m2) and platelet-to-lymphocyte ratio were independent prognostic factors of OS in patients aged ≥65 years. In conclusion, GNRI was a significant prognostic factor in advanced NSCLC patients regardless of age. A decreased GNRI may be considered as a clinical trigger for nutritional support in advanced NSCLC patients, though additional studies are still required to confirm the best cut-point.

The association between milk consumption and the metabolic syndrome: a cross-sectional study of the residents of Suzhou, China and a meta-analysis.

The association between milk consumption and the metabolic syndrome remains inconclusive, and data from Chinese populations are scarce. We conducted a cross-sectional study to investigate the association between milk consumption and the metabolic syndrome and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 5149 participants were included in the final analysis. A logistic regression model was applied to estimate the OR and 95 % CI for the prevalence of the metabolic syndrome and its components according to milk consumption. In addition, the results of our study were further meta-analysed with other published observational studies to quantify the association between the highest v. lowest categories of milk consumption and the metabolic syndrome and its components. There was no significant difference in the odds of having the metabolic syndrome between milk consumers and non-milk consumers (OR 0·86, 95 % CI 0·73, 1·01). However, milk consumers had lower odds of having elevated waist circumference (OR 0·78, 95 % CI 0·67, 0·92), elevated TAG (OR 0·83, 95 % CI 0·70, 0·99) and elevated blood pressure (OR 0·85, 95 % CI 0·73, 0·99). When the results were pooled together with other published studies, higher milk consumption was inversely associated with the risk of the metabolic syndrome (relative risk 0·80, 95 % CI 0·72, 0·88) and its components (except elevated fasting blood glucose); however, these results should be treated with caution as high heterogeneity was observed. In summary, the currently available evidence from observational studies suggests that higher milk consumption may be inversely associated with the metabolic syndrome.

Preparation of gold nanorod-incorporated monolith for solid phase extraction of polycyclic aromatic hydrocarbons.

An organic-inorganic hybrid monolithic column doped with gold nanorods (AuNRs) was prepared and evaluated for solid phase extraction (SPE) of polycyclic aromatic hydrocarbons (PAHs). Excellent dispersibility of AuNRs in binary green porogen system consisting of 1-hexyl-3-methylimidazolium tetrafluoroborate and deep eutectic solvents (DESs) was confirmed by energy dispersive spectrometry (EDS). The particle size of the resulting AuNRs (70-90 nm) was thoroughly examined by a transmission electron microscopy (TEM). The redox system including ammonium persulfate (APS) and tetramethylethylenediamine (TEMED) was used to initiate in situ polymerization at 4 °C to prepare the hybrid monolith. The mesoporous structure of the AuNR hybrid monoliths was confirmed by scanning electron microscopy (SEM) and nitrogen adsorption. With enrichment factors (EFs) of 150- to 292-fold, the developed method was successfully applied to the determination of 10 PAHs in wastewater samples. The recoveries at a spiked level were in the range 84.9 to 99.5% with limit of detections (LODs) and relative standard deviations (RSDs) ranging from 0.02 to 0.10 µg L-1 and 1.5 to 4.2%, respectively. The correlation coefficients (R2) for the calibration function obtained were better 0.9991 for the target compounds. Compared to the AuNR-free monolith, the extraction efficiency of the AuNR-incorporated monolith is more than two times higher. The results indicated that the doping of AuNRs is an effective approach to obtain the hybrid monolithic column with good separation ability for PAHs. Graphical abstract.

Body mass index, waist circumference, and risk of hearing loss: a meta-analysis and systematic review of observational study.

BACKGROUND: Emerging evidence implicates excess weight as a potential risk factor for hearing loss. However, this association remained inconclusive. Therefore, we aimed to systematically and quantitatively review the published observational study on the association between body mass index (BMI) or waist circumference (WC) and hearing loss. METHODS: The odds ratios (ORs) or relative risks (RRs) with their 95% confidence intervals (CIs) were pooled under a random-effects model. Fourteen observational studies were eligible for the inclusion in the final analysis. RESULTS: In the meta-analysis of cross-sectional studies, the ORs for prevalent hearing loss were 1.10 (95% CI 0.88, 1.38) underweight, 1.14 (95% CI 0.99, 1.32) for overweight, OR 1.40 (95% CI 1.14, 1.72) for obesity, 1.14 (95% CI 1.04, 1.24) for each 5 kg/m2 increase in BMI, and 1.22 (95% CO 0.88. 1.68) for higher WC. In the meta-analysis of longitudinal studies, the RRs were 0.96 (95% CI 0.52, 1.79) for underweight, 1.15 (95% CI 1.04, 1.27) for overweight, 1.38 (95% CI 1.07, 1.79) for obesity, 1.15 (95% CI 1.01, 1.30) for each 5 kg/m2 increase in BMI, and 1.11 (95% CI 1.01, 1.22) for higher WC. CONCLUSIONS: In summary, our findings add weight to the evidence that elevated BMI and higher WC may be positively associated with the risk of hearing loss.

Irradiated VEGF164-modified tumor cell vaccine protected mice from the parental tumor challenge.

Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine. T-cells isolated from the vaccinated mice showed cytotoxicity against the parental tumor cells in a dose-dependent manner. Meanwhile, sera from the mice vaccinated with LL/2-VEGF164 showed higher titers of antibodies against parental tumor cells compared with the nonvaccinated groups. Our results indicated that VEGF164-modified tumor vaccine could modulate host antitumor immune response and hold therapeutic potential for cancer.

MCPNET: Development of an interpretable deep learning model based on multiple conformations of the compound for predicting developmental toxicity.

The development of deep learning models for predicting toxicological endpoints has shown great promise, but one of the challenges in the field is the accuracy and interpretability of these models. The bioactive conformation of a compound plays a critical role for it to bind in the target. It is a big issue to figure out the bioactive conformation in deep learning without the co-crystal structure or highly precise molecular simulations. In this study, we developed a deep learning framework of Multi-Conformation Point Network (MCPNET) to construct classification and regression models, respectively, based on electrostatic potential distributions on vdW surfaces around multiple conformations of the compound using a dataset of compounds with developmental toxicity in zebrafish embryo. MCPNET applied 3D multi-conformational surface point cloud to extract the molecular features for model training, which may be critical for capturing the structural diversity of compounds. The models achieved an accuracy of 85 % on the classification task and R2 of 0.66 on the regression task, outperforming traditional machine learning models and other deep learning models. The key feature of our model is its interpretability with the component visualization to identify the factors contributing to the prediction and to understand the compound action mechanism. MCPNET may predict the conformation quietly close to the bioactive conformation of a compound by attention-based multi-conformation pooling mechanism. Our results demonstrated the potential of deep learning based on 3D molecular representations in accurately predicting developmental toxicity. The source code is publicly available at https://github.com/Superlit-CC/MCPNET.

Comprehensive hepatotoxicity prediction: ensemble model integrating machine learning and deep learning.

Background: Chemicals may lead to acute liver injuries, posing a serious threat to human health. Achieving the precise safety profile of a compound is challenging due to the complex and expensive testing procedures. In silico approaches will aid in identifying the potential risk of drug candidates in the initial stage of drug development and thus mitigating the developmental cost. Methods: In current studies, QSAR models were developed for hepatotoxicity predictions using the ensemble strategy to integrate machine learning (ML) and deep learning (DL) algorithms using various molecular features. A large dataset of 2588 chemicals and drugs was randomly divided into training (80%) and test (20%) sets, followed by the training of individual base models using diverse machine learning or deep learning based on three different kinds of descriptors and fingerprints. Feature selection approaches were employed to proceed with model optimizations based on the model performance. Hybrid ensemble approaches were further utilized to determine the method with the best performance. Results: The voting ensemble classifier emerged as the optimal model, achieving an excellent prediction accuracy of 80.26%, AUC of 82.84%, and recall of over 93% followed by bagging and stacking ensemble classifiers method. The model was further verified by an external test set, internal 10-fold cross-validation, and rigorous benchmark training, exhibiting much better reliability than the published models. Conclusion: The proposed ensemble model offers a dependable assessment with a good performance for the prediction regarding the risk of chemicals and drugs to induce liver damage.

Effective induction therapy with subcutaneous administration of bortezomib for newly diagnosed POEMS syndrome: a case report and a review of the literature.

POEMS syndrome is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Bortezomib is an important component of the chemotherapy regimen associated with multiple myeloma, and has been previously applied to POEMS syndrome. We present a 56-year-old Chinese man who was given subcutaneous administration of bortezomib as part of the BDex (bortezomib-dexamethasone) regimen for his POEMS syndrome. The peripheral neuropathy and laboratory-test results of the patient improved dramatically with 4 cycles of treatment, resulting in a complete response. In addition, the treatment was well tolerated and adequate peripheral blood hematopoietic stem cells were collected for an ensuing autologous stem cell transplant.

Graphene oxide used as a carrier for adriamycin can reverse drug resistance in breast cancer cells.

This study evaluates the reversal effects of graphene oxide (GO) used as a carrier for adriamycin (ADR) in cancer drug resistance, and provides a preliminary investigation into the reversal mechanism. ADR was loaded onto the GO surface (ADR-GO) by physical mixing and drug loading content was found to be high, up to 93.6%. In vitro releases of ADR from ADR-GO were studied using a dialysis method, and they exhibited a significant pH-sensitive property. Cell experiments showed that GO significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher cytotoxicity than free ADR, suggesting that ADR-GO could effectively reverse ADR resistance of MCF-7/ADR, with the reversal index reaching 8.35. Microscopy studies found that GO could effectively carry drug molecules into cells in both endocytosis-dependent and independent manners. In conclusion, use of GO as a carrier for chemotherapeutic agents is favorable for the treatment of drug resistant cancers.

[Characteristics of the patients with primary Sjögren's syndrome complicated with lymphoma].

OBJECTIVE: To improve the understanding of diagnosis and treatment of patients with primary The data of clinical features, laboratory Sjögren's syndrome (pSS) complicated with lymphoma. METHODS: findings, therapeutic response and follow-up of patients with primary Sjögren's syndrome complicated with lymphoma from January 2006 to January 2011 in our single center were retrospectively analyzed. RESULTS: Totally twelve inpatients with pSS complicated with lymphoma were diagnosed, which accounted for 1.29% of newly-diagnosed lymphoma inpatients during the same period. The characteristic immunologic changes were hyperimmunoglobulinemia, hypocomplementemia and decrease of CD4 T cell number. In our study, non-Hodgkin's lymphoma (NHL) was the most common type, and the main pathological subtype was diffuse large B cell lymphoma (DLBCL). Most of the patients were in advanced stages, Ann Arbor stage IIl-IV, at diagnosis. Extranodal involvement was common, most frequently in the livers and the lungs. All of the patients received combination chemotherapy. Most of the NHL patients received CHOP/R-CHOP-like regimens, and the Hodgkin's lymphoma (HL) patient received AVD regimen. The median follow-up time was 27 months (range 1-56 months). In terms of median survival time and overall survival there were no statistical significant differences between both low C3 and low C4 group and control group (P > 0.05). In terms of median survival time and overall survival there were no statistical significant differences between rituximab treatment group and control group (P > 0.05). CONCLUSION: The patients with pSS complicated with lymphoma were not uncommon clinically. Hypocomplementemia could not be identified as a risk factor for the prognosis of pSS complicated with lymphoma in our study. Although expected prognosis of these patients was unfavorable, we found that treatment with rituximab combination chemotherapy could not improve the therapeutic effects and survival of patients with pSS complicated with lymphoma.

[Effect of diagnostic ultrasound-mediated microbubble contrast and urokinase on augmentation thrombolysis and optimization of the major parameters: an in vitro study].

OBJECTIVE: To investigate the efficacy of diagnostic ultrasound and microbubble contrast (MB) on enhancing thrombolysis in combination with urokinase (UK) and to determine the optimal combination for thrombolysis in vitro. METHODS: Four types of standardized red thrombus were prepared in vitro, including 3-hour-old (3 h), 6-hour-old (6 h), 12-hour-old (12 h), and 24-hour-old (24 h). The major parameters for the designed experiments included transmit powers of ultrasound (factor A, 5%, 25%, 50%, 100%), MB volumes (factor B, 50 microL, 100 microL, 200 microL, 400 microL), UK concentrations (factor C, 100 U/mL, 200 U/mL, 400 U/mL, 800 U/mL), and lysis time (factor D, 10 min, 20 min, 30 min, 40 min). An orthogonal array experimental design (OAD) based on four levels L16 (4(5)) of the above four parameters was employed to optimize the thrombolysis conditions. During the procedure of thrombolysis, the diagnostic ultrasound frequency was fixed at 1.82 MHz. The histopathological changes measured by HE staining and scanning electron microscope (SEM) were carried out to observe the clots before and after thrombolysis. The loss of clot weight before and after treatment was measured to determine the lysis efficiency (LE). Analysis of variance (ANOVA) was performed to assess the LE according to the L16 (4(5)) matrix. RESULTS: The HE staining and SEM observation of thrombolysis under the following experimental conditions of 5% ultrasound transmit power, 400 microL MB volume, 800 U/mL UK concentration, and 40 min lysis time showed remarkable disaggregation of fibrin nets. The above four factors had significant impact on thrombus (all P < 0.05), among which UK concentrations (factor C) was the most significant one. The optimal scheme was determined as a C4-D4-A1-B4 mode, with UK concentration 800 U/mL, lysis time 40 min, transmit power 5%, and MB volume 400 microL, respectively. The LE curves for 3h clots were superior to the others. The lysis efficiencies for the clots showed significant differences among different type of thrombus (all P < 0.05). CONCLUSION: 1.82 MHz diagnostic ultrasound and microbubble contrast can be applied to augment thrombolysis in vitro even with a transmit power as low as 5%. Under the condition of fixed ultrasound frequency, the LE of thrombus increase with increased UK concentrations, lysis time and MB volumes, and decrease with increased thrombus ages.

Reliable CA-(Q)SAR generation based on entropy weight optimized by grid search and correction factors.

Chromosome aberration (CA) is a serious genotoxicity of a compound, leading to carcinogenicity and developmental side effects. In the present manuscript, we developed a QSAR model for CA prediction using artificial intelligence methodologies. The reliable QSAR model was constructed based on an enlarged data set of 3208 compounds by optimizing machine learning and deep learning algorithms based on hyperparametric iterations and using multiple descriptors of molecular fingerprint in combination with drug-like molecular properties (MP) screened by entropy weight methodology on the open-source Python platform. Furthermore, molecular similarity for returning search and molecular connection index for additional descriptor were additionally introduced to differentiate the compounds with high similarity for correct CA prediction for QSAR model generation. The final generated CA-(Q)SAR model exhibited good prediction accuracy of 80.6%. The bias of the final model is about 0.9793. On the basis of generated QSAR model, data analyses were further performed to analyze the typical structure features in numerical intervals (MPI) of molecular properties MW, XlogP, and TPSA, respectively, for potential CA or non-CA toxicity with a normalized occurrence probability (NOP) more than 70%, which may provide useful clues for drug design of leads or candidate devoid of CA genotoxicity.

[Role of DNMT3a in Hydroquinone-Induced Hematopoietic Stem Cell Toxicity].

OBJECTIVE: To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity. METHODS: Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively. RESULTS: Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001). CONCLUSION: DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.

Novel combined shield design for eye and face protection from COVID-19.

The World Health Organization emphasized the importance of goggles and face shields for protection of medical personnel at the outbreak of the COVID-19 pandemic. Unsurprisingly, almost all countries suffered from a critical supply shortage of goggles and face shields, as well as many other types of personal protective equipment (PPE), for a long period, owing to the lack of key medical material supplies and the inefficiency of existing fabrication methods arising from the need to avoid crowds during the outbreak of COVID-19. In this paper, we propose a novel combined shield design for eye and face protection that can be rapidly fabricated using three-dimensional printing technology. The designed prototype eye-face shield is accessible to the general public, offering more possibilities for yield improvement in PPE during emergent infectious disease events such as COVID-19.

[Effects of WNK1 on Human Chronic Myeloid Leukemia K562 Cells via MAPK7 Phosphorylation and Its Relative Mechanism].

OBJECTIVE: To investigate the biological effects and mechanism of WNK1 on K562 cells through regulating MAPK7. METHODS: Cells were routinely cultured in vitro, the expression of WNK1 and MAPK7 in different blood tumor cell lines was analyzed by RT-qPCR and Western blot analysis.K562 cells were transfected with siRNA-WNK1 lentivirus.The effect of WNK1 on K562 cell proliferation was analyzed by using CCK-8 reagent.And K562 cell apoptosis was analyzed by using flow cytometry. The expression level of phosphorylated MAPK7 protein and total MAPK7 protein in K562 cells was analyzed by Western blot. RESULTS: The mRNA and protein of WNK1 were highly expressed in HL60, THP-1, U266 and K562 cells, however, the expressions were the highest in K562 cells (P<0.05), while the changes of mRNA and protein expressions of MAPK7 were not significantly in HL60, THP-1, U266 and K562 cells (P>0.05), but the phosphorylated MAPK7 expression was the highest in K562 cells (P<0.05). Proliferation of K562 cells transfected by WNK siRNA was significantly suppressed, and apoptosis was obviously increased (P<0.05). And the pMAPK7 protein expression in K562 cells transfected by WNK1 siRNA significantly decreased (P<0.05), however, the total MAPK7 protein expression in K562 cells showed no obvious change (P>0.05). CONCLUSION: WNK1 is highly expressed in K562 cells, which can promote the proliferation of K562 cells and reduce apoptosis probably by promoting phosphorylation of its downstream MAPK7.

Lactoferrin Alleviates the Progression of Atherosclerosis in ApoE-/- Mice Fed with High-Fat/Cholesterol Diet Through Cholesterol Homeostasis.

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.

Post-diagnostic C-reactive protein and albumin predict survival in Chinese patients with non-small cell lung cancer: a prospective cohort study.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80-3.04) and 2.64 (95% CI: 1.35-5.16) for patients in the second and the highest tertiles of CRP (P-trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29-0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15-7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.