Greenhouse gas emission inventory of drinking water treatment plants and case studies in China.

The Chinese government claimed to reach carbon dioxide emissions peaking by 2030 and achieve carbon neutralization by 2060. In this context, it's meaningful and urgent to estimate GHG emissions amount in every sectors. The growing concern about reducing GHG emissions has been shared by many water companies. This work aims to identify and estimate GHG emissions from the activities of drinking water treatment plants (DWTPs). According to the GHG protocol, the GHG emission inventory of DWTPs covers the sources of fossil fuel combustion, reservoir emissions, electricity and heat supply, use of chemicals and additives, disposal of waste, transportation, operation and maintenance. The tool was tested by nine DWTPs, which had an average GHG emission intensity of 0.225 kg CO2-eq/m3. The GHG emission intensities range from 0.167 kg CO2-eq/m3 to 0.272 kg CO2-eq/m3. The main source of GHG emissions is electricity supply, followed by the use of chemicals and additives. According to the average emission intensity, the estimated total amount of GHG emissions from DWTPs in China is about 1.82 × 107 t/a, corresponding to 0.15 % of the total GHG emission in China. The proposed GHG sources and emissions help decision-makers and DWTPs companies estimate GHG emissions more accurately and undertake GHG reduction measures.

An injectable and active hydrogel induces mutually enhanced mild magnetic hyperthermia and ferroptosis.

Magnetic hyperthermia therapy (MHT) is a promising new modality to deal with solid tumors, yet the low magnetic-heat conversion efficacy, magnetic resonance imaging (MRI) artifacts, easy leakage of magnetic nanoparticles, and thermal resistance are the main obstacles to expand its clinical applications. Herein, a synergistic strategy based on a novel injectable magnetic and ferroptotic hydrogel is proposed to overcome these bottlenecks and boost the antitumor efficacy of MHT. The injectable hydrogel (AAGel) exhibiting a sol-gel transition upon heating is made of arachidonic acid (AA)-modified amphiphilic copolymers. Ferrimagnetic Zn0.4Fe2.6O4 nanocubes with high-efficiency hysteresis loss mechanism are synthesized and co-loaded into AAGel with RSL3, a potent ferroptotic inducer. This system maintains the temperature-responsive sol-gel transition, and provides the capacity of multiple MHT and achieves accurate heating after a single injection owing to the firm anchoring and uniform dispersion of nanocubes in the gel matrix. The high magnetic-heat conversion efficacy of nanocubes coupled with the application of echo limiting effect avoids the MRI artifacts during MHT. Besides the function of magnetic heating, Zn0.4Fe2.6O4 nanocubes combined with multiple MHT can sustain supply of redox-active iron to generate reactive oxygen species and lipid peroxides and accelerate the release of RLS3 from AAGel, thus enhancing the antitumor efficacy of ferroptosis. In turn, the reinforced ferroptosis can alleviate the MHT-triggered thermal resistance of tumors by impairment of the protective heat shock protein 70. The synergy strategy achieves the complete elimination of CT-26 tumors in mice without causing local tumor recurrence and other severe side effects.

Healthy Eating Index-2015 in relation to risk of metabolic dysfunction-associated fatty liver disease among US population: National Health and Nutrition Examination Survey 2017-2018.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a serious chronic disease in the US. Dietary patterns provide good guidance for the prevention of chronic diseases. The Healthy Eating Index (HEI-2015) is a dietary pattern based on the dietary characteristics of the US. Objective: Since the relation between HEI-2015 and MAFLD is unclear, this study examined their associations using the US National Health and Nutrition Examination Surveys (NHAENS) during 2017-2018. Methods: This study included data from 4,062 participants aged ≥20 years, without viral hepatitis or pregnancy. MAFLD is defined as hepatic steatosis with one or more of the following: (1) overweight or obesity (body mass index ≥25 kg/m2); (2) type 2 diabetes; or (3) two or more other metabolic risk abnormalities. HEI-2015 scores were calculated from food intake information collected by the 24-h meal review method. The relationship of HEI-2015 with MAFLD was calculated using survey-weighted logistic regression analysis after adjusting for sex, age, race, education level, smoking status, alcohol use, levels of C-reactive protein, Aspartate Aminotransferase, Alanine Aminotransferase, a body shape index, minutes of sedentary activity, levels of cholesterol and glucose, energy take, drugs use, hypertension, and diabetes. Results: When compared to the study population with no MAFLD, the patients with MAFLD showed a lower weighted mean HEI (48.0 ± 0.6). HEI-2015 was inversely associated with MAFLD in the fully adjusted model [Q4 vs. Q1, OR = 0.567 (0.407-0.790), P = -0.002]. Among the 13 HEI-2015 components, total vegetables, greens and beans, total fruits, whole fruits, and whole grains were negatively associated with MAFLD, while added sugars were positively associated with MAFLD. This inverse association was consistent in subgroups of the participants stratified by sex, age, education level, race, body shape index, minutes of sedentary activity, hypertension, and diabetes. Conclusion: A higher HEI-2015 is associated with a lowered risk of MAFLD which is more obvious among participations who were women, young, Mexican Americans, with higher education, and with no hypertension or diabetes.

A Prognostic Nomogram of Colon Cancer With Liver Metastasis: A Study of the US SEER Database and a Chinese Cohort.

BACKGROUND: Among colon cancer patients, liver metastasis is a commonly deadly phenomenon, but there are few prognostic models for these patients. METHODS: The clinicopathologic data of colon cancer with liver metastasis (CCLM) patients were downloaded from the Surveillance, Epidemiology and End Results (SEER) database. All patients were randomly divided into training and internal validation sets based on the ratio of 7:3. A prognostic nomogram was established with Cox analysis in the training set, which was validated by two independent validation sets. RESULTS: A total of 5,700 CCLM patients were included. Age, race, tumor size, tumor site, histological type, grade, AJCC N status, carcinoembryonic antigen (CEA), lung metastasis, bone metastasis, surgery, and chemotherapy were independently associated with the overall survival (OS) of CCLM in the training set, which were used to establish a nomogram. The AUCs of 1-, 2- and 3-year were higher than or equal to 0.700 in the training, internal validation, and external validation sets, indicating the favorable effects of our nomogram. Besides, whether in overall or subgroup analysis, the risk score calculated by this nomogram can divide CCLM patients into high-, middle- and low-risk groups, which suggested that the nomogram can significantly determine patients with different prognosis and is suitable for different patients. CONCLUSION: Higher age, the race of black, larger tumor size, higher grade, histological type of mucinous adenocarcinoma and signet ring cell carcinoma, higher N stage, RCC, lung metastasis, bone metastasis, without surgery, without chemotherapy, and elevated CEA were independently associated with poor prognosis of CCLM patients. A nomogram incorporating the above variables could accurately predict the prognosis of CCLM.

Durable super-hydrophobic PDMS@SiO2@WS2 sponge for efficient oil/water separation in complex marine environment.

The robust and eco-friendly super-hydrophobic sponge with remarkable performances has been potential adsorption material for the treatment of offshore oil spills. In this work, the durable PDMS@SiO2@WS2 sponge was fabricated via a green and facile one-step dipping method. The mixed tungsten disulfide (WS2) microparticles and hydrophobic SiO2 nanoparticles were immobilized on the sponge by non-toxic polydimethylsiloxane (PDMS) glue tier, which featured the hierarchical structure and extreme water repellency with the water contact angle of 158.8 ± 1.4°. The obtained PDMS@SiO2@WS2 sponge exhibits high oil adsorption capacity with 12-112 times of its own weight, and oil/water selectivity with separation efficiency over 99.85%. Notably, when subjected to the complex marine environment including high temperature, corrosive condition, insolation, and strong wind and waves, the modified sponge can maintain sable super-hydrophobicity with water contact angle over 150°. Moreover, it possesses superior mechanical stability for sustainable reusability and oil recovery. The sponge fabricated by non-toxic modifiers along with its sable super-hydrophobicity in complex marine environment makes it a potential material for practical applications.

Green synthesized iron nanoparticles as highly efficient fenton-like catalyst for degradation of dyes.

Iron nanoparticles (Fe NPs) were synthesized herein through a simple and eco-friendly method using FeCl3 and aqueous plant extract (dimocarpus longan, DL). Compared with Fe NPs prepared via traditional chemical methods, this biogenetic DL-Fe NPs demonstrates higher catalytic activity in Fenton-like reaction to degrade methyl orange (MO) in a wide pH range. It's worth noting that the DL-Fe NPs manifest a superior stability even after storage for at least 28 days. Systematic characterizations indicate that the active biomolecules from plant extract significantly contribute to the superior performance of DL-Fe NPs, by facilitating the dye molecules to be adsorbed on the surfaces of DL-Fe NPs, and providing a stable acid environment for the Fenton-like catalytic reaction. The kinetics study demonstrates this removal process conforms to the pseudo first-order model with the reaction activation energy of 41.6 kJ/mol. Moreover, various typical dyes including congo red, malachite green, methylene blue, eosin-Y and rhodamine B can be dramatically degraded by this DL-Fe NPs with a satisfactory removal efficiency.

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance.

BACKGROUND: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP - GC). METHODS: The clinical, gene expression profile data and AS events of 138 HP - GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP - GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan-Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP - GC. Finally, splicing networks were constructed using Cytoscape. RESULTS: A total of 48141 AS events and 1041 DEAS events were found in HP - GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. CONCLUSION: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP - GC and can be used as prognostic factors to establish an effective nomogram.

Cyclic AMP represses pathological MEF2 activation by myocyte-specific hypo-phosphorylation of HDAC5.

Class IIa histone deacetylases (HDACs) critically regulate cardiac function through the repression of the activity of myocyte enhancer factor 2 (MEF2)-dependent gene programs. Protein kinase D (PKD) and Ca2+/Calmodulin-dependent kinase II (CaMKII) activate MEF2 by phosphorylating distinct HDAC isoforms and thereby creating 14-3-3 binding sites for nucleo-cytoplasmic shuttling. Recently, it has been shown that this process is counteracted by cyclic AMP (cAMP)-dependent signaling. Here, we investigated the specific mechanisms of how cAMP-dependent signaling regulates distinct HDAC isoforms and determined their relative contributions to the protection from pathological MEF2 activation. We found that cAMP is sufficient to induce nuclear retention and to blunt phosphorylation of the 14-3-3 binding sites of HDAC5 (Ser259/498) and HDAC9 (Ser218/448) but not HDAC4 (Ser246/467/632). These regulatory events could be observed only in cardiomyocytes and myocyte-like cells but not in non-myocytes, pointing to an indirect myocyte-specific mode of action. Consistent with one previous report, we found that blunted phosphorylation of HDAC5 and HDAC9 was mediated by protein kinase A (PKA)-dependent inhibition of PKD. However, we show by the use of neonatal cardiomyocytes derived from genetic HDAC mouse models that endogenous HDAC5 but not HDAC9 contributes specifically to the repression of endogenous MEF2 activity. HDAC4 contributed significantly to the repression of MEF2 activity but based on the mechanistic findings of this study combined with previous results we attribute this to PKA-dependent proteolysis of HDAC4. Consistently, cAMP-induced repression of agonist-driven cellular hypertrophy was blunted in cardiomyocytes deficient for both HDAC5 and HDAC4. In conclusion, cAMP inhibits MEF2 through both nuclear accumulation of hypo-phosphorylated HDAC5 and through a distinct HDAC4-dependent mechanism.

Biogenic Pt/CaCO3 Nanocomposite as a Robust Catalyst toward Benzene Oxidation.

Fabricating the highly dispersive and stable Pt nanoparticles (NPs) on an economical and environmentally friendly support is of great concern in the field of catalysis. Herein, a waste eggshell was used as the support to prepare supported Pt catalysts through a plant-mediated biosynthesis method, in which the Pt precursor was reduced to Pt NPs by employing Cacumen platycladi (CP) leaf extract. The temperature and atmosphere for thermal treatment of such eggshell-supported Pt catalysts were assessed to understand their effects on catalytic performance toward the oxidation of benzene. The optimal Pt/eggshell-Ar (calcined at 400 °C in Ar) demonstrated that the temperature required for 90% benzene conversion (T90%) was as low as 178 °C (80 000 mL g-1 h-1) and could operate steadily for at least 300 h of onstream reaction. The structure of the catalyst after reaction is much the same as that of the unreacted one. Transmission electron microscopy (TEM), thermogravimetry (TG), and X-ray photoelectron spectroscopy (XPS) results showed that Pt NPs were evenly distributed on the eggshell supports, and the calcination conditions had important influences on the residual CP leaf extract, the average Pt NPs size, and the ratio of Pt0/Pt2+ over the catalysts. Density functional theory (DFT) calculations indicated that the interactions between Pt NPs and porous CaCO3 could promote benzene activation adsorbed onto the Pt NPs. In addition, biogenic Pt catalysts were proved to overtake the chemically reduced counterparts in the field of catalytic performance; furthermore, both biogenic and chemically reduced Pt NPs supported on the eggshell demonstrated preferable catalytic activity than that of commercial 5Pt/C (com-Pt/C) catalysts. Collectively, immobilizing biogenic noble metal active components on the eggshell-based support could be a promising approach for the preparation of supported noble metal catalysts with excellent catalytic performance toward catalytic oxidation of volatile organic compounds (VOCs).

High-Flux and Robust Co3O4 Mesh for Efficient Oil/Water Separation in Harsh Environment.

Material with special wettability for oil/water separation has drawn more and more attention, since the oil spill accidents and industrial processing are growing in frequency and in volume. A superhydrophilic and underwater superoleophobic mesh was prepared by introducing Co3O4 on a stainless steel mesh, through a simple hydrothermal process and subsequent calcination. The as-prepared Co3O4 mesh can not only separate various oil/water mixtures with high efficiency and high flux, but also work effectively in harsh environment such as highly acidic, alkaline, and salty solutions. Moreover, the Co3O4 mesh can still retain good separation performance after 40 abrasion cycles with sandpaper. The outstanding anticorrosion and antiabrasion behaviors make the Co3O4 mesh promising for oil/water separation even in harsh environment.

Formate-assisted analytical pyrolysis of kraft lignin to phenols.

The effect of sodium formate (SF), calcium formate (CF) and nickel formate (NF) as additives on analytical pyrolysis performance of kraft lignin was conducted. The results showed that these formates promoted the releasing of volatiles, leading to the rapid degradation of kraft lignin. High relative content of monophenols (53.77%), especially of guaiacol (23.65%), were achieved from the pyrolysis of pure lignin. The relative content of guaiacol was dramatically decreased after the adding of formates in kraft lignin. The relative content of polyphenols such as 3-methylcatechol and 4-methylcatechol reached to 16.97%, 16.23% and 21.95% with the formates of SF, CF and NF, respectively. The NF showed the highest selectivity of polyphenols and hydrocarbons. The increase of polyphenols and hydrocarbons from NF was the synergetic effect of the hydrogen radical reaction from the formic functional groups under the catalysis of Ni and/or NiO produced from the NF pyrolysis process.

Comprehensive pharmacological profiling of neurofibromatosis cell lines.

Patients with Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) are predisposed to tumors of the nervous system. NF1 patients predominantly develop neurofibromas, and Malignant Peripheral Nerve Sheath Tumors (MPNST) while NF2 patients develop schwannomas and meningiomas. Here we quantified the drug sensitivities of NF1 and NF2 tumor cell lines in a high throughput platform. The platform contained a comprehensive collection of inhibitors of MEK, RAF, RAS, farnesyl transferase, PAK and ERK, representative drugs against many other cancer pathways including Wnt, Hedgehog, p53, EGF, HDAC, as well as classical cytotoxic agents recommended for treating MPNST, such as doxorubicin and etoposide. We profiled seven NF1-associated MPNST cell lines (ST88-14, ST88-3, 90-8, sNF02.2, T265, S462TY, SNF96.2), one sporadic MPNST cell line (STS26), one schwannoma from a NF2 patient (HEI193), one NF2-deficient malignant meningioma (KT21-MG-Luc5D), one mouse NF2 schwannoma (SC4) and one sporadic rat schwannoma (RT4-67 or RT4). NF1 cells were primarily distinguished from NF2 cells and the sporadic MPNST cell line by their sensitivity to MEK and ERK inhibitors, and to a smaller extent their sensitivity to BH3 mimetics and farnesyl transferase inhibitors. The platform was highly successful in predicting the effects of clinical trials for Neurofibromas.

Simultaneous determination of seven nitrogen-containing phenyl ethers in cosmetics by gas chromatography with mass spectrometry and dispersive solid-phase extraction.

An analytical method was established for the simultaneous determination of seven nitrogen-containing phenyl ethers (2-anisidine, 3-anisidine, 4-anisidine, 2-nitroanisole, 3-nitroanisole, 4-nitroanisole, and 3,3'-dimethoxybenzidine) in cosmetics by gas chromatography with mass spectrometry in this work. The samples were extracted with ethyl acetate and purified with primary secondary amine during the dispersed solid-phase extraction. The analytes were separated by a DB-17MS column and detected in the electron ionization mode of mass spectrometry in the selected ions monitoring mode. The extraction solvent, purification adsorbents, and chromatographic column behavior were optimized. The results indicated that the seven analytes show good linear relationship (R2 > 0.9965) in the concentrations of 5.0-5000 µg/L. The quantitation limits of the method ranged from 19.0 to 84.8 µg/kg. The recovery rates of seven analytes were in the range of 72.6-114% with the relative standard deviations of 1.1-7.5%. Real sample analyses showed that this accurate and precise method could be appropriate for simultaneous determination of seven nitrogen-containing phenyl ethers in cosmetics.

Comparative effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in advanced gastric cancer: A meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Platinum-based drugs are the most significant chemotherapy for advanced gastric cancer. The study aims to compare the efficacy and safety of oxaliplatin-based therapy versus cisplatin-based therapy in patients with advanced gastric cancer. MATERIALS AND METHODS: An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in patients with advanced gastric cancer were eligible. The primary endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. RESULTS: Five phase II or III RCTs involving a total of 2,046 patients were identified. The results showed that there were no significant difference in ORR (OR = 1.17, 95% CI = 0.98-1.40, p = 0.08, I2 = 0%), PFS (HR = 0.92, 95% CI = 0.84-1.01, p = 0.09, I2 = 0%) and OS (HR = 0.91, 95% CI = 0.82-1.01, p = 0.07, I2 = 0%) between oxaliplatin-based therapy and cisplatin-based therapy. In addition, oxaliplatin-based therapy had lower risk of neutropenia, anemia, nausea, alopecia, thromboembolism, stomatitis and creatinine increased at all grades, and neutropenia, anemia, leukopenia and alopecia at 3-4 grades than cisplatin-based therapy. However, oxaliplatin-based therapy was associated with increased risk of neurosensory toxicity and thrombocytopenia. CONCLUSIONS: Our meta-analysis showed that there were no significant difference in ORR, PFS and OS between oxaliplatin-based therapy and cisplatin-based therapy. The oxaliplatin-based therapy could generally decrease the risk of adverse effects except neurosensory toxicity and thrombocytopenia.

Plant-mediated synthesis of highly active iron nanoparticles for Cr (VI) removal: Investigation of the leading biomolecules.

The eco-friendly synthesis and application of Fe nanoparticles (Fe NPs) with higher activity and stability has aroused wide attention in the field of pollutant remediation. In this work, 15 plants extracts were selected for the plant-mediated synthesis of Fe NPs. The as-synthesized particles' morphology and structure were characterized by transmission electron microscopy, X-ray diffraction and UV-Vis spectroscopy. The contents of four main active biomolecules in the 15 extracts were determined, and comparative studies were further carried out to clarify the key component closely related to the reducing capacity. The results demonstrate that polyphenol is the leading ingredient involved in the biosynthesis of Fe NPs. Then Fe products synthesized by three extracts with distinct content of polyphenol were employed to remove Cr (VI) in the aqueous solution, indicating that the activity of the Fe NPs for Cr (VI) removal is consistent with the reducing capacity of the extracts. Furthermore, the Fe NPs synthesized by S. jambos（L.） Alston extract (SJA-Fe NPs) showed significant removal capacity of Cr(VI) with 698.6 mg Cr(VI) per g of iron.

Role for intravesical prostatic protrusion in lower urinary tract symptom: a fluid structural interaction analysis study.

BACKGROUND: Numerous studies indicated that Intravesical prostatic protrusion is relevant to prognosis of LUTS, however, the confounding effect that is brought about by prostate volume, urethra anterior curvature angle and other factors makes it hard to evaluate the role of intravesical prostatic protrusion in clinical observation. METHODS: We proposed a fluid structural interaction analysis approach. 3D models were constructed based on MRI images, and prostatic urethra diameters were calibrated with urodynamic data. Comparisons of urine flow dynamics were made between models with various degree of intravesical prostatic protrusion, while the intravesical pressure, anterior urethra curvature angle and diameter of prostatic urethra were same among all models to rule out their confounding effects. RESULTS: Simulation result showed that the decrement of diameter and increment of variation in cross-sectional area for prostatic urethra were related to the degree of intravesical prostatic protrusion. Such deformation would lead to deterioration of flow efficiency and could compromise the effect of bladder outlet obstruction alleviation treatment. CONCLUSIONS: These results provided further evidence for intravesical prostatic protrusion being an independent risk factor for bladder outlet obstruction severity and demonstrated that intravesical prostatic protrusion would be a promising marker in clinical decision making.

Safety profile of combined therapy inhibiting EFGR and VEGF pathways in patients with advanced non-small-cell lung cancer: A meta-analysis of 15 phase II/III randomized trials.

The efficacy of combined vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibition in patients with advanced non-small-cell lung cancer (NSCLC) was well studied. However, few studies focused on the risk and adverse events (AEs) of combined targeted therapy. The aim of this meta-analysis was to evaluate the safety profile of combined targeted therapy against EFGR and VEGF in patients with advanced NSCLC. A comprehensive literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts and ESMO Abstracts was conducted. Eligible studies were randomized clinical trials (RCTs) that compared safety profile of combined therapy inhibiting EFGR and VEGF pathways with control groups (placebo, single EGFR or VEGF inhibition therapy, chemotherapy or a combination of them) in patients with advanced NSCLC. The endpoints included treatment discontinuation, treatment-related deaths and AEs. The search identified 15 RCTs involving 6,919 patients. The outcomes showed that three of four pairwise comparisons detected more discontinuation due to AEs in combined targeted therapy, with odds ratio (OR) compared with the control groups ranged from 1.97 to 2.29. Treatment with combined inhibition therapy was associated with several all-grade and grade 3 or 4 AEs (e.g. rash, diarrhea and hypertension). Also, there was a significantly higher incidence of treatment-related deaths in combined inhibition using vandetanib versus single EGFR inhibition therapy (OR = 1.97, 95% CI 1.19-3.28). In conclusion, combined inhibition therapy against EGFR and VEGF in patients with advanced NSCLC was associated with increased toxicity. Increased AEs hinder patient compliance and reduce their quality of life, leading to dose reduction or discontinuation.