Heterogeneous catalytic oxidation of glycerol over a UiO-66-derived ZrO2@C supported Au catalyst at room temperature.

The catalytic conversion of biomass-derived glycerol into high-value-added products, such as glyceric acid (GLYA), using catalyst-supported Au nanoparticles (Au NPs) at room temperature presents a significant challenge. In this study, we constructed a series of supported Au catalysts, including Au/ZrO2@C, Au/C, Au/ZrO2, and Au/ZrO2-C, and investigated their effectiveness in selectively catalytic oxidizing glycerol to GLYA at room temperature. Among these catalysts, the Au/ZrO2@C catalyst exhibited the best catalytic performance, achieving a glycerol conversion rate of 73% and a GLYA selectivity of 79% under the optimized reaction conditions (reaction conditions: 30 mL 0.1 M glycerol, glycerol/Au = 750 mol mol-1, T = 25 °C, p(O2) = 10 bar, stirring speed = 600 rpm, time = 6 h). Physical adsorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and other characterization methods were employed to analyze the texture properties of the catalyst. The findings indicated that the support structure, the strong metal-support interactions between Au NPs and the support, and the presence of small metallic Au NPs were the primary factors contributing to the catalyst's high activity and selectivity. Moreover, the reusability of the Au/ZrO2@C catalyst was investigated, and a probable reaction mechanism for the oxidation of glycerol was proposed.

Cardiovascular safety of Janus kinase inhibitors in patients with rheumatoid arthritis: systematic review and network meta-analysis.

Background: Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete determination of their cardiovascular safety remains inconclusive. Hence, the primary objective of this network meta-analysis is to meticulously assess and juxtapose the cardiovascular risks linked to distinct JAK inhibitors employed in RA patients. Methods: A systematic review and network meta-analysis were meticulously conducted, encompassing a collection of randomized controlled trials (RCTs) that focused on investigating the incidence of major adverse cardiovascular events (MACE) and all-cause mortality associated with Janus kinase (JAK) inhibitors administered to patients with rheumatoid arthritis (RA). Extensive exploration was performed across multiple electronic databases, incorporating studies published until March 2023. To be included in this analysis, the RCTs were required to involve adult participants diagnosed with RA who received treatment with JAK inhibitors. To ensure accuracy, two authors independently undertook the selection of eligible RCTs and meticulously extracted aggregate data. In order to examine the outcomes of MACE and all-cause mortality, a frequentist graph theoretical approach within network meta-analyses was employed, utilizing random-effects models. Third study has been registered on PROSPERO under the reference CRD42022384611. Findings: A specific selection encompassing a total of 14 meticulously chosen randomized controlled trials was undertaken, wherein 13,524 patients were assigned randomly to distinct treatment interventions. The analysis revealed no notable disparity in the occurrence of major adverse cardiovascular events (MACE) between the interventions and the placebo group. However, in comparison to adalimumab, the employment of JAK inhibitors exhibited an association with higher rates of all-cause mortality [odds ratio (OR): 1.7, 95% confidence interval (CI): 1.02-2.81]. This observed increase in risk primarily stemmed from the usage of tofacitinib (OR: 1.9, 95% CI: 1.12-3.23). None of the other JAK inhibitors exhibited a statistically significant variance in all-cause mortality when compared to adalimumab. Interpretation: Our study suggests that JAK inhibitors may not increase the risk of MACE in RA patients but may be associated with a higher risk of all-cause mortality compared to adalimumab, primarily due to tofacitinib use. Rheumatologists should carefully consider the cardiovascular risks when prescribing JAK inhibitors, particularly tofacitinib, for RA patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384611, CRD42022384611.

Saline-Alkaline Stress Resistance of Cabernet Sauvignon Grapes Grafted on Different Rootstocks and Rootstock Combinations.

Grafting the wine grape variety Cabernet Sauvignon onto salinity-tolerant rootstocks can improve salinity tolerance and grape yields in regions with high salinity soils. In this experiment, the effects of different rootstocks and rootstock combinations on the saline-alkaline stress (modified Hoagland nutrient solution + 50 mmol L-1 (NaCl + NaHCO3)) of Cabernet Sauvignon were studied. Correlation and principal component analyses were conducted on several physiological indicators of saline-alkaline stress. Salinity limited biomass accumulation, induced damage to the plant membrane, reduced the chlorophyll content and photosynthetic capacity of plants, and increased the content of malondialdehyde, sodium (Na+)/potassium (K+) ratio, and antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase). Significant differences in several indicators were observed among the experimental groups. The results indicate that the saline-alkaline tolerance of Cabernet Sauvignon after grafting was the same as that of the rootstock, indicating that the increased resistance of Cabernet Sauvignon grapes to saline-alkaline stress stems from the transferability of the saline-alkaline stress resistance of the rootstock to the scion.

Efficient removal of Cr from aqueous solution by catechol/m-phenylenediamine nanospheres combined with Fe(II).

The discharge of chromium-containing wastewater in industrial production causes resource loss and damage to the ecological environment. Currently, various phenolamine materials have been used to remove chromium, but their harsh adsorption conditions bring many difficulties. For example, ideal chromium removal is only achieved at low pH. In this study, we synthesized catechol/m-phenylenediamine nanospheres (CMN) and combined CMN with Fe(II) for Cr removal from aqueous solutions, and Fe(II) comes from FeSO4·7H2O. CMN was characterized and analyzed by field-emission scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Fourier transformed infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS). The adsorption performance was studied through a series of adsorption experiments. When C0 = 900 mg/L and pH = 6, the maximum adsorption capacity obtained in the experiment was 977.1 mg/g. It maintains excellent adsorption properties in acidic, neutral and alkaline environments. The results of the adsorption mechanism showed that the ultra-high adsorption capacity of CMN and Fe(II) for Cr was the result of the synergistic effect of adsorption and reduction, including electrostatic attraction, reduction and coprecipitation. CMN is expected to be an ideal adsorbent for Cr removal in aqueous solution due to its low cost, high biocompatibility and high efficiency in Cr removal.

Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

Development of Child-Friendly Lisdexamfetamine Chewable Tablets Using Ion Exchange Resin as a Taste-Masking Carrier Based on the Concept of Quality by Design (QbD).

Taste masking is critical to improving the compliance of pediatric oral dosage forms. However, it is challenging for extremely bitter lisdexamfetamine dimesylate (LDX) with a long half-life and given in large dose. The present study aims to develop an immediate-release, taste-masked lisdexamfetamine chewable tablet. Lisdexamfetamine-resin complexes (LRCs) were prepared using the batch method. The molecular mechanism of taste masking was explored by PXRD, PLM, STA, and FT-IR. The results showed that taste masking was attributed to the ionic interaction between drug and the resin. The ion exchange process conformed to first-order kinetics. The rate-limiting step of drug release was the diffusion of ions inside the particles, and the concentration of H+ was the key factor for immediate release. The masking efficiency of the prepared LRCs in saliva exceeded 96%, and the drug could be completely released within 15 min in aqueous HCl (pH 1.2). Furthermore, the SeDeM expert system was used for the first time to comprehensively study the powder properties of LRCs and to quickly visualize their defects (compressibility, lubricity/stability, and lubricity/dosage). The selection of excipients was targeted rather than traditional screening, thus obtaining a robust chewable tablet formulation suitable for direct compression. Finally, the difference between chewable tablets containing LRCs and chewable tablets containing lisdexamfetamine dimesylate was compared by in vitro dissolution test, electronic tongue, and disintegration test. In conclusion, an immediate-released, child-friendly lisdexamfetamine chewable tablets without bitterness was successfully developed by the QbD approach, using the SeDeM system, which may help in further development of chewable tablets.

Oral Application of Mother's Own Milk for Reducing Necrotizing Enterocolitis in Preterm Infants: An Updated Meta-Analysis of RCTs.

Background: Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are the major contributors to mortality and morbidity in preterm infants. This updated meta-analysis was aimed to assess the effects of mother's milk on the incidence of NEC, LOS, and other clinical outcomes in preterm infants. Methods: PubMed, Embase, and the Cochrane library were searched for papers published up to October 2022. Results: A total of 13 RCTs with 1330 infants were included in the final analysis. Significant difference in NEC (stage 2 or 3) was found between the intervention group and the control group (RR = 0.508, 95% CI: 0.314-0.822, and P=0.008). The incidence of proven LOS (RR = 0.809, 95% CI: 0.610-1.071, and P=0.139) and death (RR = 0.800, 95% CI: 0.571-1.122, and P=0.196) was comparable between the two groups. Statistical differences in the incidence of proven or probable LOS (RR = 0.705, 95% CI: 0.577-0.862, and P=0.001) and length of hospitalization (WMD = -4.868, 95% CI: -6.608 to -3.128, and P < 0.001) between the intervention group and the control group were observed. Conclusions: The results of this updated meta-analysis showed that compared to the placebo, mother's milk provides better effects in reducing the incidences of NEC, proven or probable LOS, and the length of stay, whereas no significant benefit of mother's milk was observed in reducing the incidence of proven LOS and death.

Influence of rootstock on endogenous hormones and color change in Cabernet Sauvignon grapes.

Different rootstocks for grapes can significantly affect fruit color and quality, possibly by affecting hormone contents, related genetic pathways, and fruit coloring mechanisms in skin. 'Cabernet Sauvignon' was grafted to '5BB', 'SO4', '140R', 'CS', '3309M' and 'Vitis riparia' rootstocks, with self-rooting seedlings as the control (CS/CS), and sampled from the early stage of veraison to the ripening stage. The effects of rootstock on the contents of gibberellin (GA3), auxin (IAA), and abscisic acid (ABA) in grape skin were determined alongside the expression levels of eight anthocyanin synthesis related genes using real-time fluorescence quantitative PCR methods. The rootstock cultivars exhibited accelerated fruit color change, and the CS/140R combination resulted in grapes with more color than the control group in the same period. With the development of fruit, the IAA and GA3 contents in the skin of different rootstock combinations showed trends of increasing initially, then decreasing, while the ABA content decreased initially and then increased. During the verasion (28 July), the various 'Cabernet Sauvignon' rootstock combinations exhibited varying degrees of increases in GA3, ABA, and IAA contents; correlation analysis showed that, at the start of veraison, the expression levels of the anthocyanin synthesis-related genes VvCHS, VvDFR, and VvUFGT had strong positive correlations with hormone contents, which indicated they are key genes involved in the endogenous hormone responsive anthocyanin biosynthesis pathway. The results of this study showed that rootstock regulates the fruit coloring process by influencing the metabolism level of peel hormones in the 'Cabernet Sauvignon' grape.

Efficacy, safety and immunogenicity of etanercept biosimilars versus reference biologics in patients with rheumatoid arthritis: A meta-analysis.

Background: Although with the application of etanercept biosimilars in the field of rheumatoid arthritis, the evidences of their efficacy, safety, and immunogenicity are still limited. We conducted this meta-analysis to evaluate the efficacy, safety and immunogenicity of etanercept biosimilars for treating active rheumatoid arthritis compared to reference biologics (Enbrel®). Methods: PubMed, Embase, Central, and ClinicalTrials.gov were searched for randomized controlled trials of etanercept biosimilars treated in adult patients diagnosed with rheumatoid arthritis from their earliest records to 15 August 2022. The outcomes included ACR20, ACR50, and ACR70 response rate at different time points from FAS or PPS, adverse events, and proportion of patients developed anti-drug antibodies. The risk of bias of each included study was assessed using the revised Cochrane Risk of Bias in Randomised Trials tool, and the certainty of evidence was rated according to the Grading of Recommendation Assessment, Development, and Evaluation. Results: Six RCTs with 2432 patients were included in this meta-analysis. Etanercept biosimilars showed more benefits in ACR50 at 24 weeks from PPS [5 RCTs, OR = 1.22 (1.01, 1.47), p = 0.04, I 2 = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I 2 = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I 2 = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I 2 = 0%, high certainty]. In terms of other outcomes about efficacy, safety, and immunogenicity, the results showed that there was no significant difference between etanercept biosimilars and reference biologics, and the certainty of evidences ranged from low to moderate. Conclusion: Etanercept biosimilars showed more benefits in ACR50 response rate at 1 year than reference biologics (Enbrel®), other outcomes for clinical efficacy, safety, and immunogenicity of etanercept biosimilars were comparable with originator in patients with rheumatoid arthritis. Systematic Review Registration: PROSPERO, identifier CRD42022358709.

Meta-analysis of the effect of PGM on survival prognosis of tumor patients.

Objective: A systematic evaluation of the impact of phosphoglucose translocase PGM on the survival prognosis of tumor patients was conducted to understand its impact on tumors so as to improve the quality of survival and to find effective therapeutic targets for tumor patients. Methods: The following were searched in the databases China National Knowledge Infrastructure (CNKI), Wanfang, Wipu, PubMed, EMBASE, ScienceDirect, Web of Science, and Cochrane Library: "PGM1", "PGM2", "PGM3", "PGM4", and "PGM5" as Chinese keywords and "PGM1", "PGM2", "PGM3", "PGM4", "PGM5", "PGM1 cancer", "PGM2 cancer", "PGM3 cancer", "PGM4 cancer", "PGM5 cancer", and "phosphoglucomutase". Relevant studies published from the database establishment to April 2022 were collected. Studies that met the inclusion criteria were extracted and evaluated for quality with reference to the Cochrane 5.1.0 systematic evaluation method, and quality assessment was performed using RevMan 5.3 software. Results: The final results of nine articles and 10 studies with a total of 3,806 patients were included, including 272 patients in the PGM1 group, 541 patients in the PGM2 group, 1,775 patients in the PGM3 group, and 1,585 patients in the PGM5 group. Results of the meta-analysis: after determining the results of the nine articles, it was found that the difference was statistically significant with a p-value <0.05 (hazard ratio (HR) = 0.89, 95% CI 0.69-1.09, p = 0.000). To find the sources of heterogeneity, the remaining eight papers were tested after removing the highly sensitive literature, and the results showed I2 = 26.5%, p < 0.001, a statistically significant difference. The HR for high expression of PGM1 and PGM2 and PGM5 was <1, while the HR for high expression of PGM3 was >1. Conclusion: Although PGM1, PGM2, PGM3, and PGM5 are enzymes of the same family, their effects on tumors are different. High expression of PGM1, PGM2, and PGM5 can effectively prolong the overall survival of patients. In contrast, high expression of PGM3 reduced the overall survival of patients. This study of PGM family enzymes can assist in subsequent tumor diagnosis, treatment, and prognostic assessment.

Catalytic Oxidation of Glycerol over Pt Supported on MOF-Derived Carbon Nanosheets.

A series of nitrogen-doped porous carbon nanosheets (NPCNs) doped with transition-metal-supported Pt catalysts were prepared by colloidal deposition and evaluated for the selective oxidation of glycerol to glyceric acid (GLYA) under nonalkaline conditions. The transition metal contained in the catalyst was found to affect its performance and selectivity for GLYA, with the Pt/Zr@NPCN catalyst showing the highest catalytic activity and selectivity. These materials were characterized using Brunauer-Emmett-Teller surface area analysis, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature-programmed desorption. The results showed that the small size of the Pt nanoparticles, the interaction between the Pt nanoparticles and the support, and the unique textural properties of the catalyst all promoted glycerol conversion and GLYA selectivity. A Zr concentration of 1.5 wt % and a support preparation temperature of 800 °C were found to provide a catalyst with the optimal performance that exhibited a glycerol conversion and selectivity for GLYA of 68.62 and 77.29%, respectively, at an initial O2 pressure of 10 bar and 60 °C after 6 h. Even after being recycled five times, this material provided a GLYA selectivity of approximately 75%, although the glycerol conversion decreased from 68 to 50%. The insights may provide new suggestions on the design of efficient support for the selective oxidation of polyols.

ST8SIA6-AS1 Promotes the Epithelial-to-Mesenchymal Transition and Angiogenesis of Pituitary Adenoma.

To investigate the effect of long noncoding RNA ST8SIA6-AS1 on the epithelial-to-mesenchymal transition (EMT) and angiogenesis of pituitary adenoma and its possible mechanism. The expression levels of ST8SIA6-AS1 and HOXA9 in noninvasive pituitary adenoma and invasive pituitary adenoma were detected using qRT-PCR. sh-ST8SIA6-AS1 transfection silenced the expression of ST8SIA6-AS1 in GH3 and GTI-1 cells. The effects of ST8SIA6-AS1 on the proliferation, invasion, angiogenesis, and EMT of GH3 and GTI-1 pituitary adenoma cells were detected. The migration ability of cells was detected through scratch assay. Dual luciferase analysis verified the targeting relationship between ST8SIA6-AS1 and miR-5195-3p. ST8SIA6-AS1 and HOXA9 were highly expressed in invasive pituitary adenoma. In pituitary adenomas, miR-5195-3p directly targeted HOXA9. miR-5195-3p is the target gene of ST8SIA6-AS1. ST8SIA6-AS1 knockdown inhibited the proliferation, invasion, angiogenesis, and EMT of pituitary adenoma. HOXA9 expression mediates the biological effect of ST8SIA6-AS1. ST8SIA6-AS1 targets miR-5195-3p to regulate the expression of HOXA9 and promote the EMT of pituitary adenomas.

Immune Infiltration Characteristics and a Gene Prognostic Signature Associated With the Immune Infiltration in Head and Neck Squamous Cell Carcinoma.

Background: Immunotherapy has become the new standard of care for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and PD-L1 is a widely used biomarker for immunotherapeutic response. However, PD-L1 expression in most cancer patients is low, and alternative biomarkers used to screen the population benefiting from immunotherapy are still being explored. Tumor microenvironment (TME), especially tumor immune-infiltrating cells, regulates the body's immunity, affects the tumor growth, and is expected to be a promising biomarker for immunotherapy. Purpose: This article mainly discussed how the immune-infiltrating cell patterns impacted immunity, thereby affecting HNSCC patients' prognosis. Method: The immune-infiltrating cell profile was generated by the CIBERSORT algorithm based on the transcriptomic data of HNSCC. Consensus clustering was used to divide groups with different immune cell infiltration patterns. Differentially expressed genes (DEGs) obtained from the high and low immune cell infiltration (ICI) groups were subjected to Kaplan-Meier and univariate Cox analysis. Significant prognosis-related DEGs were involved in the construction of a prognostic signature using multivariate Cox analysis. Results: In our study, 408 DEGs were obtained from high- and low-ICI groups, and 59 of them were significantly associated with overall survival (OS). Stepwise multivariate Cox analysis developed a 16-gene prognostic signature, which could distinguish favorable and poor prognosis of HNSCC patients. An ROC curve and nomogram verified the sensitivity and accuracy of the prognostic signature. The AUC values for 1 year, 2 years, and 3 years were 0.712, 0.703, and 0.700, respectively. TCGA-HNSCC cohort, GSE65858 cohort, and an independent GSE41613 cohort proved a similar prognostic significance. Notably, the prognostic signature distinguished the expression of promising immune inhibitory receptors (IRs) well and could predict the response to immunotherapy. Conclusion: We established a tumor immune cell infiltration (TICI)-based 16-gene signature, which could distinguish patients with different prognosis and help predict the response to immunotherapy.

lncRNA KCNQ1OT1 Promotes EMT, Angiogenesis, and Stemness of Pituitary Adenoma by Upregulation of RAB11A.

This study is aimed at investigating the effect and mechanism of long noncoding RNA (lncRNA) KCNQ1OT1 on pituitary adenoma (PA). The KCNQ1OT1 expression in invasive and noninvasive PA tissues was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). The effects of KCNQ1OT1 on the proliferation of PA cells, namely, GH3 and HP75, were detected by CCK-8 experiment. The Transwell assay detected the effect of KCNQ1OT1 on the invasion of GH3 and HP75 cells. The effect of KCNQ1OT1 on the clonal formation ability was detected by clonal formation experiment. The double luciferase reporter assay and the miRNA pull down assay verified the binding of KCNQ1OT1 to miR-140-5p. Meanwhile, the regulatory effect of miR-140-5p on RAB11A was verified. qPCR results showed that KCNQ1OT1 was significantly increased in invasive PA compared with noninvasive PA tissues. Knockdown KCNQ1OT1 inhibited PA cell stemness, angiogenesis, and EMT. In addition, knockdown KCNQ1OT1 inhibited the proliferation, invasion, and clonal formation of PA. miR-140-5p is the target gene of KCNQ1OT1. miR-140-5p targets RAB11A directly. RAB11A can mediate the biological effects of KCNQ1OT1. Meanwhile, lncRNA KCNQ1OT1 can promote the EMT and cellular stemness of PA. Its mechanism of action is realized by inhibiting miR-140-5p. This result can provide a molecular basis for the further study of PA.

Analytical Lifecycle Management (ALM) and Analytical Quality by Design (AQbD) for analytical procedure development of related substances in tenofovir alafenamide fumarate tablets.

Analytical procedure development for quantifying 10 impurities in Tenofovir Alafenamide Fumarate (TAF) tablets was a challenge for analytical and formulation researchers. The aim of this paper was to develop a robust, regulatory-flexible, application-specific Ultra Performance Liquid Chromatography (UPLC) analytical procedure using the Analytical Lifecycle Management (ALM) and the Analytical Quality by Design (AQbD) for the estimation of the TAF tablets. In this work, the Analytical Target Profile (ATP) for the analytical procedure and the Critical Analytical Attributes (CAAs) were identified. Through the risk assessment studies, the high-risk analytical conditions were found, and they were screened and optimized by the Design of Experiment (DoE) to obtain the Design Space (DS) and identify the working point. The prediction intervals were used to examine the robustness of the analytical procedure. And the procedure performance qualification and the continued procedure performance verification were used to ensure routine application of analytical procedure. Finally, the 10 impurities were separated within 20 min by UPLC. The success of this study demonstrates the usefulness of using ALM and AQbD for analytical procedure development and provides a reference for the analytical procedure development for other drugs.

Heptadecanoic acid and pentadecanoic acid crosstalk with fecal-derived gut microbiota are potential non-invasive biomarkers for chronic atrophic gastritis.

Background: Chronic atrophic gastritis (CAG), premalignant lesions of gastric cancer (GC), greatly increases the risk of GC. Gastroscopy with tissue biopsy is the most commonly used technology for CAG diagnosis. However, due to the invasive nature, both ordinary gastroscope and painless gastroscope result in a certain degree of injury to the esophagus as well as inducing psychological pressure on patients. In addition, patients need fast for at least half a day and take laxatives. Methods: In this study, fecal metabolites and microbiota profiles were detected by metabolomics and 16S rRNA V4-V5 region sequencing. Results: Alteration of fecal metabolites and microbiota profiles was found in CAG patients, compared with healthy volunteers. To identify the most relevant features, 7 fecal metabolites and 4 microbiota were selected by random forest (RF), from A and B sample sets, respectively. Furthermore, we constructed support vector machines (SVM) classifification model using 7 fecal metabolites or 4 gut microbes, or 7 fecal metabolites with 4 gut microbes, respectively, on C sample set. The accuracy of classifification model was 0.714, 0.857, 0.857, respectively, and the AUC was 0.71, 0.88, 0.9, respectively. In C sample set, Spearman's rank correlation analysis demonstrated heptadecanoic acid and pentadecanoic acid were signifificantly negatively correlated to Erysipelotrichaceae_UCG-003 and Haemophilus, respectively. We constructed SVM classifification model using 2 correlated fecal metabolites and 2 correlated gut microbes on C sample set. The accuracy of classification model was 0.857, and the AUC was 0.88. Conclusion: Therefore, heptadecanoic acid and pentadecanoic acid, crosstalk with fecal-derived gut microbiota namely Erysipelotrichaceae_UCG-003 and Haemophilus, are potential non-invasive biomarkers for CAG diagnosis.

Analysis of risk factors related to acute radiation dermatitis in breast cancer patients during radiotherapy.

Aims: To investigate the incidence and influencing factors of acute radiation dermatitis (ARD) induced by radiotherapy in postoperative patients with breast cancer. Methods and Materials: A retrospective analysis was conducted on 598 patients with breast cancer who received postoperative radiotherapy from November 18, 2014 to September 14, 2019. The radiotherapy technology included two-dimensional radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and tomotherapy. The occurrence of ARD in patients was then followed up and recorded. The independent risk factors for radiation-induced dermatitis were analyzed by using an orderly logistic regression model. Results: Of the 598 patients, 431 had mild skin reactions, including pigmentation and dry desquamation (grade 1), 151 developed wet desquamation and tender erythema (grade 2), and 16 had severe skin reactions, including flaky wet scaling and erosion (grade 3). There were no grade 4 skin reactions. The severity of ARD was independent of the following factors: Age, diabetes, allergy, quadrant, pathological type, the clinical stage, the tumor stage, triple-negative breast cancer, ki-67 expression, adjuvant chemotherapy, endocrine therapy, targeted therapy, radiotherapy area, and boost irradiation. However, it was found to be dependent on the body mass index, surgery type, radiotherapy technique, node stage, and the prophylactic use of topical agents. Conclusions: ARD in response to postoperative radiotherapy in patients with breast cancer is common and mild. Clinicians and patients need to cultivate awareness of the potential risk factors involved and then intervene to alleviate skin reactions and improve the quality of life.

A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer.

Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC). Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database. Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and protein levels in BC. Both methylation and methylation-based gene prognostic signatures showed good prognostic stratification ability. The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively. In the validation groups, high-risk patients were confirmed to have poorer OS. The AUC values of 3 years were 0.757, 0.735, 0.733 in the three subgroups of TCGA dataset and 0.635 in GSE146558 dataset. Conclusion: This study revealed the DNA methylation landscape and established promising methylation and methylation-based gene prognostic signatures that could serve as potential prognostic biomarkers and therapeutic targets.

Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab.

BACKGROUND: Cisplatin-based concurrent chemoradiotherapy is standard of care for locally advanced head and neck cancers (LAHNC). Nedaplatin, lobaplatin and nimotuzumab have shown anti-cancer effect with less gastrointestinal toxicity and nephrotoxicity. However, the profile of hematological toxicities of these agents in combination with radiotherapy has not been fully illustrated. METHODS: We retrospectively collected the clinical data of consecutive LAHNC patients treated by cisplatin-, nedaplatin-, lobaplatin-, and nimotuzumab-based concurrent chemoradiotherapy. Routine blood cell counts were obtained every 4 to 7 days. Hematological toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. RESULTS: A total of 181 eligible LAHNC patients were assigned to nimotuzumab group (n = 34), cisplatin group (n = 52), nedaplatin group (n = 62) or lobaplatin group (n = 33). Among the four groups, nimotuzumab group displayed lightest hematological toxicities, followed by cisplatin group, nedaplatin group, and lobaplatin group. Lobaplatin was more likely to produce grade 3/4 leukopenia compared with cisplatin (48.5% vs 25.0%). Compared with cisplatin, nedaplatin and lobaplatin were more likely to cause grade 3/4 thrombocytopenia (nedaplatin 19.4% vs cisplatin 3.8%; lobaplatin 30.3% vs cisplatin 3.8%). Similarly, nimotuzumab group showed highest nadir levels among the four groups, followed by cisplatin, nedaplatin, and lobaplatin group. Moreover, concurrent platinum treatment and induction chemotherapy were risk factors of developing grade 3/4 hematological toxicities. CONCLUSION: Nimotuzumab-based concurrent chemoradiotherapy in head and neck cancers produced the lightest hematological toxicities, followed by cisplatin, nedaplatin, and lobaplatin. Patients should be given specific attention during concurrent chemoradiotherapy, particularly in the presence of previous induction chemotherapy.