A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. METHODS: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). FINDINGS: Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. CONCLUSIONS: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. FUNDING: Shanghai Henlius Biotech, Inc.

Butane Tetracarboxylic Acid Grafted on Polymeric Nanofibrous Aerogels for Highly Efficient Protein Absorption and Separation.

Developing high-performance and low-cost protein purification materials is of great importance to meet the demands for highly purified proteins in biotechnological industries. Herein, a facile strategy was developed to design and construct high-efficiency protein absorption and separation media by combining aerogels' molding techniques and impregnation processes. Poly (ethylene-co-vinyl alcohol) (EVOH) nanofibrous aerogels (NFAs) were modified by grafting butane tetracarboxylic acid (BTCA) over them in situ. This modification was carried out using polyphosphoric acid as a catalyst. The resulting EVOH/BTCA NFAs exhibited favorable comprehensive properties. Benefiting from the highly interconnected porous structure, good underwater compressive properties, and abundant absorption ligands, the obtained EVOH/BTCA NFAs possessed a high static absorption capacity of 1082.13 mg/g to lysozyme and a short absorption equilibrium time of about 6 h. A high saturated dynamic absorption capacity for lysozyme (716.85 mg/g) was also realized solely by gravity. Furthermore, EVOH/BTCA NFAs displayed excellent reusability, good acid and alkaline resistance, and unique absorption selectivity performance. The successful synthesis of such aerogels can provide a potential candidate for next-generation protein absorbents for bio-separation and purification engineering.

Self-Assembly Study of Block Copolypeptoids in Response to pH and Temperature Stimulation.

Polypeptoids with well-designed structures have the ability to self-assemble into nanomaterials, which have wide potential applications. In this study, a series of diblock copolypeptoids were synthesized via ring-opening polymerization followed by click chemistry and exhibited both temperature and pH stimulation responsiveness. Under specific temperature and pH conditions, the responsive blocks in the copolypeptoids became hydrophobic and aggregated to form micelles. The self-assembly process was monitored using the UV-Vis and DLS methods, which suggested the reversible transition of free molecules to micelles and bigger aggregates upon instituting temperature and pH changes. By altering the length and proportion of each block, the copolypeptoids displayed varying self-assembly characteristics, and the transition temperature could be tuned. With good biocompatibility, stability, and no cytotoxicity, the polypeptoids reported in this study are expected to be applied as bionanomaterials in fields including drug delivery, tissue engineering, and intelligent biosensing.

Enhancing Electrochemical Performance of Aluminum-Oxygen Batteries with Graphene Aerogel Cathode.

Aluminum-oxygen batteries (AOBs) own the benefits of high energy density (8.14 kWh kg-1 ), low cost, and high safety. However, the design of a cathode with high surface area, structure integrity, and good catalytic performance is still challenging for rechargeable AOBs. Herein, the fabrication of a robust self-supporting cathode using 3D graphene aerogel (3DGA) for rechargeable AOBs is demonstrated. Electroanalysis showed that the 3DGA presented good catalytic activity in both oxygen reduction and evolution reactions, which allowed the AOB to operate for >90 cycles with low overpotentials at a current density of 0.2 mA cm-2 , and a high Coulombic efficiency of ca. 99% using ionic liquid as electrolyte. In comparison, the cell with the carbon paper cathode can only cycle for 50 rounds. The excellent cyclic performance can be attributed to the porous structure, large surface area, good electric conductivity, and catalytic activity of the 3DGA, which is prospective to be applied for other metal-air batteries, fuel cells, and supercapacitors.

The Developmental Toxicity and Endocrine-Disrupting Effects of Fenpropathrin on Gobiocypris rarus during the Early Life Stage.

In the present study, the developmental toxicity and endocrine-disrupting effects of fenpropathrin on Gobiocypris rarus during the early life stage were studied using a semi-static water exposure method. The results showed that the LOEC (lowest observed effect concentration) of fenpropathrin on the incubation of rare minnow embryos was above 2.5 µg·L-1. The LOEC and NOEC (no observed effect concentration) of fenpropathrin on the developmental malformations and death indicators were 2.0 and 1.5 µg·L-1, respectively. After exposure to 1.5 µg·L-1 of fenpropathrin for 31 days, the expressions of androgen receptor genes (AR) and sex hormone-synthesis-related genes (CYP17 and CYP19a) were significantly decreased and the expressions of thyroid hormone receptor genes (TRß) and aryl hydrocarbon receptor genes (AhR1a and AhR2) were significantly increased in juvenile Gobiocypris rarus. The expression levels of the androgen receptor gene (AR), estrogen receptor gene (ER1), and the sex hormone-synthesis-related genes (HMGR, CYP17, and CYP19a) were significantly decreased, while the estrogen receptor gene (ER2a), thyroid hormone receptor gene (TRß), and aromatic hydrocarbon receptor genes (AhR1a and AhR2) were upregulated in juvenile Gobiocypris rarus under exposure to 2.0 µg·L-1 of fenpropathrin. Relatively low concentrations of fenpropathrin can affect the expression of sex hormone receptor genes, genes related to sex hormone synthesis, thyroid hormone receptor genes, and aromatic hydrocarbon receptor genes, thus interfering with the reproductive system, thyroid system, and metabolic level in Gobiocypris rarus. Therefore, more attention should be paid to the endocrine-disrupting effect caused by the pyrethroid insecticides in the water environment. Furthermore, studies on the internal mechanism of the endocrine-disrupting effect of pyrethroid insecticides on fish is needed in the future.

HKDC1 Silencing Inhibits Proliferation and Glycolysis of Gastric Cancer Cells.

Gastric cancer (GC) is the third most lethal and fifth most common cancer in the world. In a variety of cancers, the hexokinase domain component 1 (HKDC1) is carcinogenic. This study was to investigate into how HKDC1 contributes to the development and progression of GC. Three different datasets (GSE103236, GSE13861, and GSE55696) were extracted from the Gene Expression Omnibus (GEO) database and then analyzed using the sva package. The R software was used to identify 411 differentially expressed genes (DEGs) in the pooled dataset. We discovered 326 glycolysis-related genes (glyGenes) in the cancer genome atlas-stomach adenocarcinoma (TCGA-STAD) cohort using gene set enrichment analysis set (GSEA). HKDC1 is one of the most prevalent glyGenes in GC tumor tissues and cells, as seen in the Venn diagram. According to the results of the Cell Count Kit-8 assay, the proliferation of AGS and MKN-45 cells decreased when HKDC1 was knocked down. Lack of HKDC1 in cells enhanced oxygen consumption and decreased glycolytic protein expression while suppressing glucose absorption, lactate production, ATP level, and extracellular acidification ratio. As an oncogene in gastric cancer development, HKDC1 influences cell proliferation and glycolysis.

Chitosan-based hollow nanofiber membranes with polyvinylpyrrolidone and polyvinyl alcohol for efficient removal and filtration of organic dyes and heavy metals.

Due to their large specific surface area and numerous diffusion channels, hollow fibers are widely used in wastewater treatment. In this study, we successfully synthesized a chitosan (CS)/polyvinylpyrrolidone (PVP)/polyvinyl alcohol (PVA) hollow nanofiber membrane (CS/PVP/PVA-HNM) via coaxial electrospinning. This membrane demonstrated remarkable permeability and adsorption separation. Specifically, the CS/PVP/PVA-HNM had a pure water permeability of 4367.02 L·m-2·h-1·bar-1. The hollow electrospun nanofibrous membrane exhibited a continuous interlaced nanofibrous framework structure with the extraordinary advantages of high porosity and high permeability. The rejection ratios of CS/PVP/PVA-HNM for Cu2+, Ni2+, Cd2+, Pb2+, malachite green (MG), methylene blue (MB) and crystal violet (CV) were 96.91 %, 95.29 %, 87.50 %, 85.13 %, 88.21 %, 83.91 % and 71.99 %, and the maximum adsorption capacities were 106.72, 97.46, 88.10, 87.81, 53.45, 41.43, and 30.97 mg·g-1, respectively. This work demonstrates a strategy for the synthesis of hollow nanofibers, which provides a novel concept for the design and fabrication of highly efficient adsorption and separation membranes.

Characteristic analysis of bio-oil from penicillin fermentation residue by catalytic pyrolysis.

The hazardous waste penicillin fermentation residue (PR) is a huge hazard to the environment. The bio-oil produced by the pyrolysis of the penicillin fermentation residue has the potential to become a biofuel in the future. This paper studied the pyrolysis characteristics of PR at 400°C ∼700°C. According to the weight loss and weight loss rate of PR, the whole process of pyrolysis can be divided into three stages for analysis: dehydration and volatilization, initial pyrolysis, and pyrolytic char formation. The experimental results showed that the yield of the liquid phase is the highest (33.11%) at 600°C. GC-MS analysis results showed that high temperature is beneficial to reduce the generation of oxygenated hydrocarbons (73%∼31%) and the yield of nitrogenous compounds gradually increased (19%∼43%); the yield of hydrocarbons was low in 400°C∼600°C pyrolysis (2%∼5%) but significantly increased around 700°C (22%). In the temperature range of 400°C to 700°C, the proportion of C5-C13 in bio-oil gradually increased (26%-64%), and the proportion of C14-C22 gradually decreased (47%-16%). The catalyst can increase the proportion of hydrocarbons in the bio-oil component. And the Fe2O3/HZSM-5 mixed catalyst has a significant reduction effect on oxygen-containing hydrocarbons and nitrogen-containing compounds.

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis.

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.

A Prognostic Risk Model of a Novel Oxidative Stress-Related Signature Predicts Clinical Prognosis and Demonstrates Immune Relevancy in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is among the most prevalent malignant lung cancers with a poor prognosis due to high invasiveness and lethality despite multiple treatments. Since the lung is an important organ associated with oxidative stress, and it has been confirmed that oxidative stress represents a potential cancer-specific depletion, it is of important significance to investigate and evaluate the clinical value of oxidative stress mechanisms regulating tumor cell apoptosis. Furthermore, there are few studies on the impact of the microenvironment on reaction to immune-checkpoint inhibitors (ICIs) in patients with LUAD. Based on the TCGA-LUAD dataset, which is stratified into a training set as well as a validation set in a ratio of 2 : 1, this investigation constructs and validates a prognostic predictive power of a gene signature model of oxidative stress-related prognostic signatures. To ascertain the differences between the high-risk score group and the low-risk score group in tumor-infiltrating lymphocytes and patients' response to ICI therapy. This oxidative stress-related prognostic gene signature is composed of MAP3K19 and NTSR1 and is an independent prognosis-related factor in the LUAD group. The outcome of patients having a low risk score is better, and the difference was statistically significant, and individuals with a low risk score had a larger number of infiltrating immune cell distribution in the tumor microenvironment, which was closely related to clinical outcome. Our study suggests that the synergistic effect of oxidative stress-related prognostic gene markers-MAP3K19 and NTSR1 has clinical significance in the prognosis identification and immunotherapy of LUAD patients. Thus, the results may help to better intersect the oxidative stress-related mechanisms in clinical value in LUAD but requires prospective validation.

Clinicopathological Features and Postoperative Survival Analysis of Gastric Carcinoma with Neuroendocrine Differentiation.

Objectives: This study aims at investigating the differences of clinicopathological features and postoperative prognosis in three different types of neuroendocrine differentiation-related gastric cancers. Methods: From January 1, 2015 to September 30, 2016, 47 patients diagnosed with neuroendocrine differentiation-related gastric cancers were collected from 1095 patients with gastric cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery, Jiangsu Cancer Hospital. Patients were followed up regularly, and the last follow-up time was October 25, 2021. A total of 38 cases met the inclusion criteria and completed follow-up. The clinicopathological characters and immunohistochemical results of these three special pathological types of gastric cancer (adenocarcinoma with neuroendocrine differentiation, mixed adenoneuroendocrine carcinoma, and neuroendocrine carcinoma of the stomach) patients were compared. Tissues from these patients were tested with immunohistochemical markers synaptophysin (Syn), chromogranin A (CgA), and Ki-67. The Kaplan-Meier method and log-rank test were used to analyze the effect of different histological types of gastric cancer on overall survival (OS). The differences in positive rates of chromogranin A (CgA) and Ki-67 were analyzed by univariate Cox regression analysis as independent risk factors that may affect the survival of gastric cancer patients. Results: Ki-67 and N staging were significantly correlated with OS in gastric cancer patients and were independent prognostic factors affecting the survival of gastric cancer patients. There was no statistical difference in OS between the two histopathological types (adenocarcinoma with neuroendocrine differentiation and mixed adenoneuroendocrine carcinoma) of gastric cancer patients. There were no significant differences in the positive rates of immunohistochemical markers Syn, CgA, and Ki-67 in gastric cancer patients with different histological types. Conclusion: The combined detection of Syn and CgA is of great value for the diagnosis of neuroendocrine differentiation-related gastric cancers, Ki-67 is of significance for the prognosis prediction of neuroendocrine differentiation-related gastric cancers, regional lymph node metastasis has a great impact on tumor prognosis, and the N staging determines the necessity of postoperative adjuvant chemotherapy for patients with neuroendocrine differentiation-related gastric cancer.

Expression of CircATXN7 in esophageal cancer tissues and its effect on cell proliferation and invasion.

Background: The goal of the current research was to investigate circATXN7 expression in esophageal cancer (EC) and its impact on the proliferation, migration, and invasion of EC cells. Methods: Determination of circATXN7 expression in esophageal cancer tissues and adjacent tissueswas carried out using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and we further analyzed the correlation between patients' clinical characteristics and circATXN7 expression. EC cell lines (EC-9706, Eca-109, TE-1, KYSE-30, and KYSE-150) and normal esophageal cell line (HET-1A) were cultured, and circATXN7 expression was detected by qRT-PCR. The lowest circATXN7-containing Eca-109 cells were selected to be transfected with an overexpressing lentiviral vector (circATXN7). EC-9706 cells with the highest expression of circATXN7 were selected for transfection with knockdown vectors [short hairpin RNA (shRNA)#1 and shRNA#2] of the circATXN7 sequence. Cell proliferation was determined via MTT assay. The formation of cell clones was investigated via colony formation assay. Transwell migration assay was utilized to determine cell migration and invasion ability. Results: Significantly higher levels of circATXN7 were observed in EC tissues compared with paracancerous tissues (P<0.01), and circATXN7 expression level showed a significant correlation with the tumor/lymph nodes/metastasis (TNM) stage and metastasis of lymph nodes (P<0.05). Among all esophageal cell lines, EC-9706 had the highest expression level and Eca-109 had the lowest expression level. The MTT assay revealed that circATXN7 overexpression could significantly promote the proliferation of Eca-109 cells, while circATXN7 knockdown was capable of significantly inhibiting EC cell proliferation. The colony formation experiments revealed a significant increase in the number of clones in the circATXN7 overexpression model and a significant decrease in the circATXN7 knockdown model. The results of transwell migration experiments suggested that circATXN7 overexpression could promote EC cell invasion and migration, while knockdown of circATXN7 expression was associated with significant inhibition of the invasion and migration of these cells. Conclusions: CircATXN7 exerted a critical role in the incidence and progression of EC. This study identified a novel molecular target and established a theoretical basis for the early detection and treatment of EC.

A cohort study of the efficacy and safety of immune checkpoint inhibitors plus anlotinib versus immune checkpoint inhibitors alone as the treatment of advanced non-small cell lung cancer in the real world.

Background: Anlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and has been shown to have antitumor effects and synergistic antitumor effects with immunotherapy only in animal studies and in the 2nd-line treatment in small clinical trials. A real-world study with large sample to compare the efficacy and safety of anlotinib plus immune checkpoint inhibitors (ICIs) with ICIs alone in the multiline treatment of advanced non-small cell lung cancer (NSCLC) was urgently needed. Methods: The data of 535 advanced NSCLC patients were collected from January 1, 2018, to December 31, 2021. The patients were divided into 2 groups: (I) ICI monotherapy (230 patients); (II) ICI + anlotinib (305 patients). After propensity-score matching (PSM) to reduce the effects of biases and confounding variables, the progression-free survival time (PFS), occurrence of adverse events, disease control rate (DCR), and objective response rate (ORR) of the 2 groups were compared. The effects of clinical factors, including age, gender, gene mutations, tumor proportion score, metastases, and combined radiotherapy, were also analyzed. Results: After PSM, the baseline clinical characteristics were well balanced and the 2 group had a good comparability. Patients in the ICI + anlotinib group had significantly longer median PFS in both the 2nd-line treatment (7.73 vs. 4.70 months; P=0.003) and 3rd-line treatment (5.90 vs. 3.37 months; P=0.020), but the difference lacked statistical significance in the 1st-line treatment (8.40 vs. 5.20 months; P=0.229). The overall median PFS of patients in the ICI + anlotinib group was also much longer than that of patients in the ICI monotherapy group (6.37 vs. 3.90 months; P<0.001). The ICI + anlotinib group also tended to have a higher DCR, a higher ORR, and a higher probability of severe adverse drug reactions during the treatment than the ICI monotherapy group, but the differences were not statistically significant. Combining ICI + anlotinib could improve the outcomes of patients with bone metastasis. Conclusions: Anlotinib + ICI therapy could have greater efficacy in the treatment of advanced NSCLC patients than ICI monotherapy. The probability of adverse events might increase in the combined treatment, but could be controlled.

An exploration of the clinical progression models of osimertinib in the treatment of advanced EGFR-mutant non-small cell lung cancer.

Background: Classifying the progression pattern had been proved to be momentous for predicting efficacy and guiding treatment in the 1st/2nd generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), while lack evidence in the 3rd generation EGFR-TKIs. This study aimed to classify tumor progression of osimertinib in EGFR+ advanced non-small cell lung cancer (NSCLC), exploring the characteristics and the clinical significance of each progression pattern. Methods: After screening 1,125 lung cancer patients, 168 EGFR T790M+ advanced patients using osimertinib were enrolled and divided into two groups and five clinical progression models according to the time course of the tumor progression. The prognosis and characteristics, such as gender, age, metastases, of each model were analyzed and compared by Kaplan-Meier method, t-test, and linear regression. Results: Complete follow-up data were available for 117 of the 168 patients. Progressive disease (PD) occurred in 89 patients at an average onset of 6.59 months since using osimertinib, with 79.78% of patients experiencing enlargement of some preexisting lesions before PD. Among the five progression models, the 'Rapid Enlargement' (10.11%) model, the 'Rapid New Lesion' model (10.11%), the 'Delayed Enlargement' model (29.21%), the 'Delayed New Lesion' model (15.73%), and the 'Non-targeted Enlargement' model (34.83%), the 'Non-targeted Enlargement' model had the worst prognosis, with a median progression-free survival (mPFS) of 7.1 months (P=0.046). The mPFS of other models was similar, with the largest difference in the time interval between the beginning of osimertinib treatment to the first appearance of target lesion enlargement (Tm-e). Smoking history (P=0.046) and the location of the initial (P=0.048), enlarged (P=0.003), and progressive lesions (P=0.002) affected the progression models, while gender, age, and treatment lines had no effect. The Tm-e was related to the overall disease control time with a correlation coefficient of 0.667 (P=0.000). The appearance of a malignant pleural effusion had an impact on progression. Conclusions: We tried to create a classification system for describing the failure of the third-generation EGFR-TKI osimertinib including two groups, subdivided into five progression models based on the time course of tumor lesion changes. The system might be conducive to predict the prognosis and be potential to assist in selecting subsequent treatment strategies.

Deep-learning-based analysis of preoperative MRI predicts microvascular invasion and outcome in hepatocellular carcinoma.

BACKGROUND: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC. METHODS: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated, and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression. RESULTS: Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and a-fetoprotein (AFP) were independently associated with MVI: DL-MVI (odds ratio [OR] = 35.738; 95% confidence interval [CI] 14.027-91.056; p < 0.001), AFP (OR = 4.634, 95% CI 2.576-8.336; p < 0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824. CONCLUSIONS: Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.

Preoperative Systemic Immune-Inflammation Index (SII) as a Superior Predictor of Long-Term Survival Outcome in Patients With Stage I-II Gastric Cancer After Radical Surgery.

Background: Systemic immune-inflammation index (SII), calculated by immunoinflammatory cell counts of peripheral blood, is considered a predictor of survival outcome in several solid tumors, including gastric cancer (GC). However, there is no study focusing on the prognostic value of SII in the early stage of GC. This study aims to compare prognostic prediction capabilities of several inflammatory indices, nutritional indices, and tumor markers to further verify the superior prognostic value of SII in stage I-II GC patients after surgery. Methods: In this study, 548 patients (358 in the training group and 190 in the validation group) with stage I-II GC after radical surgery were retrospectively analyzed. The peripheral blood indices of interest were SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), advanced lung cancer inflammation index (ALI), systemic inflammation score (SIS), prognostic nutritional index (PNI), body mass index (BMI), albumin, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate-associated antigen 19-9 (CA19-9), and alpha-fetoprotein (AFP). The time-dependent receiver operating characteristic (t-ROC) curves and the area under the curve (AUC) were used to determine the optimal cutoff value and prognostic ability of each parameter. Kaplan-Meier curves and multivariable Cox regression models were used to evaluate independent prognostic factors. The nomogram was constructed based on the result of bidirectional stepwise regression model. Results: The optimal cutoff value of SII was 508.3. The 5-year overall survival rate of the low SII (SII-L) group was significantly higher than that of the high SII (SII-H) group (92% vs. 80%, P < 0.001), especially in the elderly and stage II patients (91% vs. 73%, P = 0.001; 86% vs. 67%, P = 0.003, respectively). The significant prognostic values of SII were consistent in most subgroups. In multivariate analysis, SII and CA19-9 were the only two independent prognostic hematology indices. The AUC value of SII (0.624) was greater than that of CA19-9 (0.528) and other prognostic parameters. Adding SII to the conventional model improved the predictive ability of 5-year overall survival as shown by the significantly increased net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (P = 0.033, P = 0.053, respectively) and modestly improved consistency index (C-index) (increased by 1.6%). External validation of SII-based nomogram demonstrated favorable predictive performance and discrimination. In addition, interactive web dynamic nomogram was published to facilitate clinical use. Conclusion: SII is a simple but powerful index with a high predictive value to predict survival outcome in patients with stage I-II GC after radical operation. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

[Rapid determination of bisphenols in surface water by modified QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

Chromatography combined with mass spectrometry is the most commonly used detection technology, and it offers the advantages of high sensitivity and high selectivity. However, the contents of bisphenols (BPs) in water samples are at the ng/L level. Even if the BPs contents are determined by mass spectrometry, the samples must be pretreated and enriched. A quick, easy, inexpensive, effective, rugged, and safe technique (QuEChERS) can offer advantages such as cost effectiveness and time efficiency. The application of QuEChERS is currently extended to the analysis of contaminants in food and water samples. In this work, QuEChERS coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was proposed for the determination of eight BPs in surface water. Method optimization was carried out in terms of process efficiency (PE), which included the matrix effect (ME) and extraction recovery (RE). First, the water samples were extracted with 10 mL ethyl acetate and cleaned with 50 mg primary secondary amine (PSA) and 50 mg graphitized carbon black (GCB). Then, the organic layer was collected and evaporated to dryness under nitrogen flow (40 ℃). Finally, the extracts were redissolved in 0.5 mL of a methanol-water (1∶1, v/v) mixture and subjected to UPLC-MS/MS analysis. Chromatographic separation was accomplished on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) with gradient elution. Methanol and 0.1 mmol/L ammonium bicarbonate aqueous solution were used as the mobile phases. The eight BPs were analyzed by MS/MS with negative electrospray ionization (ESI-) and in the multiple reaction monitoring (MRM) mode. The matrix matching external standard method was used for quantitative determination. The eight compounds could be analyzed within 8 min. Under the optimized conditions, the calibration curves showed good linearities for the eight BPs, and the coefficients of determination (R2) were greater than 0.9990. The limits of detection (LODs, S/N=3) and limits of quantification (LOQs, S/N=10) were in the ranges of 0.1-2.3 ng/L and 0.3-6.1 ng/L, respectively. The average recoveries of the eight BPs in river water samples were 78.8%-116.6%, and the corresponding relative standard deviations (RSDs) were 1.8%-9.0% (n=6). This method was applied to the analysis of BPs pollution in Guangyuan section of Jialing river and its tributaries, and widespread pollution was confirmed. The detection rate of BPA was 100% with a content of 6.15-90.03 ng/L, and the detection rate of BPS was 91%, with the contents being in the range not detected (nd) to 4.63 ng/L. The method established in this study allowed for the rapid enrichment and purification of the eight BPs in water. With its advantages of simplicity, rapidness, high sensitivity, and low cost, the method can be used for the rapid determination of trace BPs in surface water such as lake water and river water.

Deep muscularis propria tumor invasion without lymph node metastasis as a unique subclassification of stage IB gastric cancer: a retrospective study.

BACKGROUND: The prognosis difference based on the depth of tumor muscularis propria invasion in gastric cancer (GC) was still debated, and therapy strategy for stage IB GC patient required further investigation. METHODS: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in superficial muscularis propria (sMP) group and 195 in deep muscularis propria (dMP) group. RESULTS: The overall survival (OS) was significantly better for patients in sMP group than for patients in dMP group (P = 0.007). In multivariate analysis, depth of tumor invasion, pN stage, age, primary location, positive expression of p53, elevated maximal LDH, elevated initial CA19-9 and AFP level were independent prognostic factors for OS. The sMP group had a significantly better OS than dMP group (P = 0.014) in pN0 stage. After further stratification, the survival outcomes were not significantly different between deep muscularis propria tumor invasion without lymph node metastasis (dMPN0) group (stage IB) and superficial muscularis propria tumor invasion with stage 1-2 lymph node metastasis (sMPN1-2) group (stage II) (P = 0.100). Patients with adjuvant chemotherapy had a statistically better survival than those without in dMPN0 group (P = 0.045) and dMPN0 patients with adjuvant chemotherapy had better OS than sMPN1-2 patients (P = 0.015). In addition, greater postoperative survival could be observed in sMPN0 patients than dMPN0 patients in p53-positive group (P = 0.002), and similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872). CONCLUSION: As a unique subclassification of stage IB GC, appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53, elevated LDH could be potential factors in identifying the different prognoses for stage IB GC patients.

Cross-Modal Prostate Cancer Segmentation via Self-Attention Distillation.

The automatic and accurate segmentation of the prostate cancer from the multi-modal magnetic resonance images is of prime importance for the disease assessment and follow-up treatment plan. However, how to use the multi-modal image features more efficiently is still a challenging problem in the field of medical image segmentation. In this paper, we develop a cross-modal self-attention distillation network by fully exploiting the encoded information of the intermediate layers from different modalities, and the generated attention maps of different modalities enable the model to transfer significant and discriminative information that contains more details. Moreover, a novel spatial correlated feature fusion module is further employed for learning more complementary correlation and non-linear information of different modality images. We evaluate our model in five-fold cross-validation on 358 MRI images with biopsy confirmed. Without bells and whistles, our proposed network achieves state-of-the-art performance on extensive experiments.

Differences in responses of ammonia volatilization and greenhouse gas emissions to straw return and paddy-upland rotations.

Paddy-upland rotation and/or straw return could improve soil structure and soil nutrient availability. Different previous crops (wheat and/or oilseed rape) and straw return methods (straw mulching and/or returning) might increase soil organic carbon (C) and total nitrogen (N) content, and further affected the ammonia (NH3) volatilization, nitrous oxide (N2O), and methane (CH4) emissions. A comparison study was carried out in a located field experiment started from 2014 in Central China, aiming to exam seasonal and annual NH3, N2O, and CH4 emissions under the wheat-rice (WR) and oilseed rape-rice (OR) rotations. Three treatments were chosen, i.e., (i) no chemical N fertilizer application (PK), (ii) chemical nitrogen-phosphorus-potassium combination (NPK), and (iii) chemical NPK with straw returning (NPK+St). We found that after 3 years of cultivation, treatment with straw return increased soil total N content and organic C by 15.57% and 17.11% on average as compared with the NPK treatment, respectively. Straw return did not generate additional NH3 and N2O losses during the rice season after improving soil fertility. However, CH4 emissions increased by 45.35% on average after straw return in summer. In winter, straw return increased NH3, N2O, and CH4 emissions by 70.12-85.23%, 16.93-22.97%, and 7.18-9.17%, respectively. The stimulation of NH3 volatilization mainly occurred in the topdressing stage. Compared with WR rotation, OR rotation had no significant effect on NH3 and CH4 emissions, and the change of N2O emission might be related to the increase of soil C and N pools. The retention of residues in the process of straw decomposition may be the main factor leading to the difference of gas emission between the paddy-upland rotation and straw return.