Targeting Epigenetic Crosstalk as a Therapeutic Strategy for EZH2-Aberrant Solid Tumors.

Mutations or aberrant upregulation of EZH2 occur frequently in human cancers, yet clinical benefits of EZH2 inhibitor (EZH2i) remain unsatisfactory and limited to certain hematological malignancies. We profile global posttranslational histone modification changes across a large panel of cancer cell lines with various sensitivities to EZH2i. We report here oncogenic transcriptional reprogramming mediated by MLL1's interaction with the p300/CBP complex, which directs H3K27me loss to reciprocal H3K27ac gain and restricts EZH2i response. Concurrent inhibition of H3K27me and H3K27ac results in transcriptional repression and MAPK pathway dependency in cancer subsets. In preclinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors, or a triple-combination including MAPK inhibition display robust efficacy with very tolerable toxicity. Our results suggest an attractive precision treatment strategy for EZH2-aberrant tumors on the basis of tumor-intrinsic MLL1 expression and concurrent inhibition of epigenetic crosstalk and feedback MAPK activation.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

iRice-MS: An integrated XGBoost model for detecting multitype post-translational modification sites in rice.

Post-translational modification (PTM) refers to the covalent and enzymatic modification of proteins after protein biosynthesis, which orchestrates a variety of biological processes. Detecting PTM sites in proteome scale is one of the key steps to in-depth understanding their regulation mechanisms. In this study, we presented an integrated method based on eXtreme Gradient Boosting (XGBoost), called iRice-MS, to identify 2-hydroxyisobutyrylation, crotonylation, malonylation, ubiquitination, succinylation and acetylation in rice. For each PTM-specific model, we adopted eight feature encoding schemes, including sequence-based features, physicochemical property-based features and spatial mapping information-based features. The optimal feature set was identified from each encoding, and their respective models were established. Extensive experimental results show that iRice-MS always display excellent performance on 5-fold cross-validation and independent dataset test. In addition, our novel approach provides the superiority to other existing tools in terms of AUC value. Based on the proposed model, a web server named iRice-MS was established and is freely accessible at http://lin-group.cn/server/iRice-MS.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Identification of patients with nonischemic dilated cardiomyopathy at risk of malignant ventricular arrhythmias: insights from cardiac magnetic resonance feature tracking.

BACKGROUND: Patients with nonischemic dilated cardiomyopathy (NIDCM) are prone to arrhythmias, and the cause of mortality in these patients is either end-organ dysfunction due to pump failure or malignant arrhythmia-related death. However, the identification of patients with NIDCM at risk of malignant ventricular arrhythmias (VAs) is challenging in clinical practice. The aim of this study was to evaluate whether cardiovascular magnetic resonance feature tracking (CMR-FT) could help in the identification of patients with NIDCM at risk of malignant VAs. METHODS: A total of 263 NIDCM patients who underwent CMR, 24-hour Holter electrocardiography (ECG) and inpatient ECG were retrospectively evaluated. The patients with NIDCM were allocated to two subgroups: NIDCM with VAs and NIDCM without VAs. From CMR-FT, the global peak radial strain (GPRS), global longitudinal strain (GPLS), and global peak circumferential strain (GPCS) were calculated from the left ventricle (LV) model. We investigated the possible predictors of NIDCM combined with VAs by univariate and multivariate logistic regression analyses. RESULTS: The percent LGE (15.51 ± 3.30 vs. 9.62 ± 2.18, P < 0.001) was higher in NIDCM patients with VAs than in NIDCM patients without VAs. Furthermore, the NIDCM patients complicated with VAs had significantly lower GPCS than the NIDCM patients without VAs (- 5.38 (- 7.50, - 4.22) vs.-9.22 (- 10.73, - 8.19), P < 0.01). Subgroup analysis based on LGE negativity showed that NIDCM patients complicated with VAs had significantly lower GPRS, GPCS, and GPLS than NIDCM patients without VAs (P < 0.05 for all). Multivariate analysis showed that both GPCS and %LGE were independent predictors of NIDCM combined with VAs. CONCLUSIONS: CMR global strain can be used to identify NIDCM patients complicated with VAs early, specifically when LGE is not present. GPCS < - 13.19% and %LGE > 10.37% are independent predictors of NIDCM combined with VAs.

1 H-NMR revealed pyruvate as a differentially abundant metabolite in the venom glands of Apis cerana and Apis mellifera.

As a common defense mechanism in Hymenoptera, bee venom has complex components. Systematic and comprehensive analysis of bee venom components can aid in early evaluation, accurate diagnosis, and protection of organ function in humans in cases of bee stings. To determine the differences in bee venom composition and metabolic pathways between Apis cerana and Apis mellifera, proton nuclear magnetic resonance (1 H-NMR) technology was used to detect the metabolites in venom samples. A total of 74 metabolites were identified and structurally analyzed in the venom of A. cerana and A. mellifera. Differences in the composition and abundance of major components of bee venom from A. cerana and A. mellifera were mapped to four main metabolic pathways: valine, leucine and isoleucine biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and the tricarboxylic acid cycle. These findings indicated that the synthesis and metabolic activities of proteins or polypeptides in bee venom glands were different between A. cerana and A. mellifera. Pyruvate was highly activated in 3 selected metabolic pathways in A. mellifera, being much more dominant in A. mellifera venom than in A. cerana venom. These findings indicated that pyruvate in bee venom glands is involved in various life activities, such as biosynthesis and energy metabolism, by acting as a precursor substance or intermediate product.

Improving bee feed recipes to safeguard honeybee colonies during times of food scarcity.

In beekeeping, when natural nectar or pollen sources become limited, it is crucial to provide supplemental bee feed to maintain the viability of the bee colony. This study was conducted during the autumn food shortage season, during which bees were fed with different proportions of modified bee feed. We identified an optimal bee diet by evaluating honeybee longevity, food consumption, body weight, and gut microbe distribution, with natural pollen serving as a control diet. The results indicated that bees preferred a mixture of 65% defatted soy flour, 20% corn protein powder, 13% wheat germ flour, 2% yeast powder, and a 50% sucrose solution. This bee food recipe significantly increased the longevity, feed consumption, and body weight of bees. The group fed the natural pollen diet exhibited a greater abundance of essential intestinal bacteria. The bee diets used in this study contained higher protein levels and lower concentrations of unsaturated fatty acids and vitamins than did the diets stored within the colonies. Therefore, we propose that incorporating both bee feed and natural pollen in beekeeping practices will achieve more balanced nutritional intake.

Insight into the role of stress response and toxic mechanism induced by Chloro-haloacetonitrile in vitro.

Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 µg/L and 10.7 µg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI1.5) and the phenotypic endpoint (LD50) with rp=-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.

Advances in ß-Diketocyclisation of Curcumin Derivatives and their Antitumor Activity.

Curcumin, derived from the popular spice turmeric, is a pharmacologically active polyphenol. Curcumin's therapeutic activity has been extensively studied in recent decades, with reports implicating curcumin in many biological activities, particularly, its significant anticancer activity. However, its potential as an oral administration product is hampered by poor bioavailability, which is associated with a variety of factors, including low water solubility, poor intestinal permeability, instability, and degradation at alkaline pH. To improve its bioavailability, modifying ß-diketone curcumin with heterocycles, such as pyrazole, isoxazole and triazole is a powerful strategy. Derivatives are synthesized while maintaining the basic skeleton of curcumin. The ß-diketone cyclized curcumin derivatives are regulators of multiple molecular targets, which play vital roles in a variety of cellular pathways. In some literatures, structurally modified curcumin derivatives have been compared with curcumin, and the former has enhanced biological activity, improved water solubility and stability. Therefore, the scope of this review is to report the most recently synthesized heterocyclic derivatives and to classify them according to their chemical structures. Several of the most important and effective compounds are reviewed by introducing different active groups into the ß-diketone position to achieve better therapeutic efficacy and bioavailability.

A Study on Miniaturized In-Situ Self-Calibrated Thermometers Based on Ga and Ga-Zn Fixed Points.

In order to ensure the reliability and accuracy of long-term temperature measurement where the thermometers are discommodious or even impossible to access for conventional periodical calibration, a study on miniaturized in-situ self-calibrated (MISSC) thermometers based on Ga and Ga-Zn fixed points was conducted using temperature scale transfer technology. One MISSC thermometer consists of three parts: the first is the fixed-points hardware, including a container with two cells separately filled with Ga and Ga-Zn; the second is the temperature sensing hardware, made of a Type T thermocouple; the third is the mini-power heating hardware, made of a film resistance. The measurement and calibration (M&C) system comprises a temperature measurement and data processing subsystem and a mini-power heating control subsystem. Then, an in-situ self-calibration can be carried out by mini-power heating from a room temperature of about 20 °C, and then by comparison between the measured phase transition plateau results and the standard fixed-points, i.e., Ga fixed point (about 29.76 °C) and Ga-Zn fixed point (about 25.20 °C). A series of experiments were performed, and the results show that: (1) both the proposed hardware design and the self-calibration method are feasible, and (2) the Φ16 mm × 25 mm MISSC thermometer is found to be the most miniaturized one that can realize reliable self-calibration in this study.

Being Stung Once or Twice by Bees (Apis mellifera L.) Slightly Disturbed the Serum Metabolome of SD Rats to a Similar Extent.

In most cases, the number of honeybee stings received by the body is generally small, but honeybee stings can still cause serious allergic reactions. This study fully simulated bee stings under natural conditions and used 1H Nuclear Magnetic Resonance (1H NMR) to analyze the changes in the serum metabolome of Sprague-Dawley (SD) rats stung once or twice by honeybees to verify the impact of this mild sting on the body and its underlying mechanism. The differentially abundant metabolites between the blank control rats and the rats stung by honeybees included four amino acids (aspartate, glutamate, glutamine, and valine) and four organic acids (ascorbic acid, lactate, malate, and pyruvate). There was no separation between the sting groups, indicating that the impact of stinging once or twice on the serum metabolome was similar. Using the Principal Component Discriminant Analysis ( PCA-DA) and Variable Importance in Projection (VIP) methods, glucose, lactate, and pyruvate were identified to help distinguish between sting groups and non-sting groups. Metabolic pathway analysis revealed that four metabolic pathways, namely, the tricarboxylic acid cycle, pyruvate metabolism, glutamate metabolism, and alanine, aspartate, and glutamate metabolism, were significantly affected by bee stings. The above results can provide a theoretical basis for future epidemiological studies of bee stings and medical treatment of patients stung by honeybees.

Efficacy of uniportal versus multiportal video-assisted thoracoscopic lobectomy for non-small cell lung cancer: A retrospective analysis.

Objective: To compare the uniportal and multiportal video-assisted thoracoscopic surgery (VATS) in patients with non-small-cell lung cancer (NSCLC). Methods: Medical records of 128 patients with NSCLC who underwent surgical treatment in the First School of Clinical Medicine, Southern Medical University from August 2020 to February 2022 were retrospectively analyzed. There were 60 patients who underwent uniportal VATS (UVATS group) and 68 patients underwent multiportal VATS (MVATS group). The relevant indexes, complications, postoperative pain levels and quality of life, recurrence, metastases and survival between the two groups were compared. Results: UVATS was associated with longer operation time and higher intraoperative blood loss compared to MVATS (P<0.05). The postoperative drainage volume, and the visual analogue scale (VAS) scores at 24 and 72 hours were lower in the UVATS group compared to the MVATS group, while the chest tube retention time and hospitalization time were shorter than those in the MVATS group (P<0.05). The quality of life at six months after surgery in the UVATS group was significantly higher than that in the MVATS group (P<0.05). Conclusions: UVATS and MVATS have similar outcomes in patients with NSCLC. Although UVATS surgery takes longer and is associated with more interoperative bleeding, it can reduce postoperative pain, shorten postoperative recovery time, and help further improve the quality of life of patients after surgery.

Deep-Kcr: accurate detection of lysine crotonylation sites using deep learning method.

As a newly discovered protein posttranslational modification, histone lysine crotonylation (Kcr) involved in cellular regulation and human diseases. Various proteomics technologies have been developed to detect Kcr sites. However, experimental approaches for identifying Kcr sites are often time-consuming and labor-intensive, which is difficult to widely popularize in large-scale species. Computational approaches are cost-effective and can be used in a high-throughput manner to generate relatively precise identification. In this study, we develop a deep learning-based method termed as Deep-Kcr for Kcr sites prediction by combining sequence-based features, physicochemical property-based features and numerical space-derived information with information gain feature selection. We investigate the performances of convolutional neural network (CNN) and five commonly used classifiers (long short-term memory network, random forest, LogitBoost, naive Bayes and logistic regression) using 10-fold cross-validation and independent set test. Results show that CNN could always display the best performance with high computational efficiency on large dataset. We also compare the Deep-Kcr with other existing tools to demonstrate the excellent predictive power and robustness of our method. Based on the proposed model, a webserver called Deep-Kcr was established and is freely accessible at http://lin-group.cn/server/Deep-Kcr.

One-Pot Assembly of Dual-Site-Specific Antibody-Drug Conjugates via Glycan Remodeling and Affinity-Directed Traceless Conjugation.

The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody-drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein-protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with the same payloads or with two types of payloads. The constructed dual-site ADCs showed acceptable homogeneity, excellent buffer stability, and enhanced in vitro and in vivo efficiency.

Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols.

Owing to the ubiquity of the hydroxyl group, reductive deoxygenation of alcohols has become an active research area. The classic Barton-McCombie reaction suffers from a tedious two-step procedure. New efficient methods have been developed, but they have some limitations, such as a narrow substrate scope and the use of moisture-sensitive Lewis acids. In this work, we describe the Ph3P/ICH2CH2I-promoted reductive deoxygenation of alcohols with NaBH4. The process is applicable to benzyl, allyl and propargyl alcohols, and also to primary and secondary alcohols, demonstrating a wide substrate scope and a good level of functional group tolerance. This protocol features convenient operation and low cost of all reagents.

The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents.

Chemotherapy is the mainstay in the treatment of breast cancer. However, many drugs that are commonly used in clinical practice have a high incidence of side effects and multidrug resistance (MDR), which is mainly caused by overexpression of drug transporters and related enzymes in breast cancer cells. In recent years, researchers have been working hard to find newer and safer drugs to overcome MDR in breast cancer. In this review, we provide the molecule mechanism of MDR in breast cancer, categorize potential lead compounds that inhibit single or multiple drug transporter proteins, as well as related enzymes. Additionally, we have summarized the structure-activity relationship (SAR) based on potential breast cancer MDR modulators with lower side effects. The development of novel approaches to suppress MDR is also addressed. These lead compounds hold great promise for exploring effective chemotherapy agents to overcome MDR, providing opportunities for curing breast cancer in the future.

Exploration of browning reactions during alkaline thermal hydrolysis of sludge: Maillard reaction, caramelization and humic acid desorption.

The browning reaction produces melanoidins, 5-hydroxymethylfurfural (HMF) and humic acids which influence subsequent anaerobic digestion and protein recovery. This paper systematically evaluates the variation of organics that make sludge browning with heating temperature and reaction time, the effect of browning organics on protein recovery and anaerobic digestion, and finally proposes a pathway for the occurrence of the Maillard reaction (MR) in the sludge environment. The results show that the browning of sludge hydrolysate is related to the comprehensive influence of the MR, caramelization and humic acid desorption. The increase of temperature (80 °C-150 °C) and pH (9-13) will promote the extent of browning of sludge hydrolysate, and the sludge browning reaction basically stabilizes at the reaction time of 1 h. Humic acid and melanoidin could co-precipitate with the protein, thereby reducing the purity of the recovered protein. The inhibition of anaerobic digestion starts when the melanoidin concentration is 8.01 mmol/L. The three-dimensional fluorescence, GC-MS and FT-IR analysis show that melanoidins have the same functional groups and fluorescence properties as humic acid does, and the humic acid in the supernatant of the sludge treated with ATH was not only converted at its adsorbed state, but also possibly generated by the reaction of the dissolved proteins with polysaccharides. Finally, LC-MS/MS was used to identify the intermediate products of the MR and the possible structural formula of melanoidin. This study further clarifies the browning reaction in hydrothermal sludge treatment and provides help for the accuracy of subsequent studies.

Prognostic implications of the EGFR polymorphism rs763317 and clinical variables among young Chinese lung cancer population.

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.