Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Development and validation of a lung metastases-predicting nomogram for intermediate- to high-risk differentiated thyroid carcinoma patients.

Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk. Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve. Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility. Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit.

[Box: see text].

Pursuing sustainable productivity with millions of smallholder farmers.

Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.

Exploration of the factors influencing the quality of life among adolescents during the COVID-19 pandemic: the data from a cross-sectional study in Shandong.

BACKGROUND: The COVID-19 pandemic has sparked unprecedented transformations in the lives of adolescents, with reshaping their routines, social dynamics, educational experiences, and overall well-being. Our study delves into the influence of various factors on adolescents' quality of life (QOL) among the COVID-19 pandemic in Shandong Province, China. METHODS: Employing a cross-sectional research approach combined with multivariable analysis, we scrutinize the association of demographic factors (age, gender, education level, ethnic groups, urban area, and family economic status) and health-related behaviors (sleep duration, and self-reported health status) with QOL in 9953 students. RESULTS: During the pandemic, the average QOL for adolescents in Shandong Province was 133. Our analysis revealed that sleep duration and age had statistically significant associations with total QOL, with the OR values of 1.43 (95% confidence interval (CI): 1.03 to 1.83) and 0.44 (95% CI: 0.19 to 0.70), respectively. Notably, we observed that adolescents from economically disadvantaged families, or those with poorer self-reported health status, were more likely to report lower QOL scores. CONCLUSIONS: Overall, our study highlights the potential association of sleep duration, age, family economic status, and self-reported health with the QOL of adolescents in Shandong Province during the pandemic. During similar public health crises, policymakers, educators, and healthcare providers can actively work through resource allocation and effective intervention measures towards alleviating financial burdens, improving health conditions, and ultimately enhancing the total QOL for adolescents.

99.92%-Fidelity cnot Gates in Solids by Noise Filtering.

Inevitable interactions with the reservoir largely degrade the performance of entangling gates, which hinders practical quantum computation from coming into existence. Here, we experimentally demonstrate a 99.920(7)%-fidelity controlled-not gate by suppressing the complicated noise in a solid-state spin system at room temperature. We found that the fidelity limited at 99% in previous works results from considering only static classical noise, and, thus, in this work, a complete noise model is constructed by also considering the time dependence and the quantum nature of the spin bath. All noises in the model are dynamically corrected by an exquisitely designed shaped pulse, giving the resulting error below 10^{-4}. The residual gate error is mainly originated from the longitudinal relaxation and the waveform distortion that can both be further reduced technically. Our noise-resistant method is universal and will benefit other solid-state spin systems.

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. METHODS: In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV-16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. RESULTS: Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). CONCLUSION: HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

Genetic Evidence for Colletotrichum gloeosporioides Transmission Between the Invasive Plant Ageratina adenophora and Co-occurring Neighbor Plants.

To understand the disease-mediated invasion of exotic plants and the potential risk of disease transmission in local ecosystems, it is necessary to characterize population genetic structure and spatio-temporal dynamics of fungal community associated with both invasive and co-occurring plants. In this study, multiple genes were used to characterize the genetic diversity of 165 strains of Colletotrichum gloeosporioides species complex (CGSC) isolated from healthy leaves and symptomatic leaves of invasive plant Ageratina adenophora, as well as symptomatic leaves of its neighbor plants from eleven geographic sites in China. The data showed that these CGSC strains had a high genetic diversity in each geographic site (all Hd > 0.67 and Pi > 0.01). Haplotype diversity and nucleotide diversity varied greatly in individual gene locus: gs had the highest haplotype diversity (Hd = 0.8972), gapdh had the highest nucleotide diversity (Pi = 0.0705), and ITS had the lowest nucleotide diversity (Pi = 0.0074). Haplotypes were not clustered by geographic site, invasive age, or isolation source. AMOVA revealed that the genetic variation was mainly from within-populations, regardless of geographic or isolation origin. Both AMOVA and neutrality tests indicated these CGSC strains occurred gene exchange among geographic populations but did not experience population expansion along with A. adenophora invasion progress. Our data indicated that A. adenophora primarily accumulated these CGSC fungi in the introduced range, suggesting a high frequency of CGSC transmission between A. adenophora and co-occurring neighbor plants. This study is valuable for understanding the disease-mediated plant invasion and the potential risk of disease transmission driven by exotic plants in local ecosystems.

Association of TLR4 and TLR9 gene polymorphisms with cervical HR-HPV infection status in Chinese Han population.

BACKGROUND: Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. METHODS: A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case-control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR-RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan-Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. RESULTS: The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan-Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). CONCLUSION: Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.

Prognostic value of metabolic genes in lung adenocarcinoma via integrative analyses.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant lung tumor. Metabolic pathway reprogramming is an important hallmark of physiologic changes in cancers. However, the mechanisms through which these metabolic genes and pathways function in LUAD as well as their prognostic values have not been fully established. METHODS: Four publicly available datasets from GEO and TCGA were used to identify differentially expressed genes (DEGs) in LUAD, which were then subjected to GO and KEGG pathway enrichment analysis. Associations between metabolic gene expressions with overall survival, tumor stage, TP53 mutation status, and infiltrated immune cells were investigated. Protein-protein interactions were evaluated using GeneMANIA and Metascape. RESULTS: By integrating four public datasets, 247 DEGs were identified in LUAD. These DEGs were significantly enriched in regulation of chromosome segregation, centromeric region, and histone kinase activity GO terms, as well as in cell cycle, p53 signaling pathway, metabolic pathways, and other KEGG pathways. Elevated expressions of ten metabolic genes in LUAD were significantly associated with poor survival outcomes. These metabolic genes were highly expressed in more advanced tumor stage and TP53 mutated patients. Moreover, expression levels were significantly correlated with tumor-infiltrating immune cells. PPI interaction analysis revealed that the top 20 genes interacting with each metabolic gene were significantly enriched in DNA replication, response to radiation, and central carbon metabolism in cancer. CONCLUSION: This study elucidates on molecular changes in metabolic genes in LUAD, which may inform the development of genetically oriented diagnostic approaches and effective treatment options.

A novel three-dimensional-printed patient-specific sacral implant for spinopelvic reconstruction in sacral giant cell tumour.

PURPOSE: Spinopelvic reconstruction after sacral tumour resection is one of the most demanding procedures in sacral tumour surgery. The aims of this study were to evaluate the feasibility of spinopelvic reconstruction with 3D-printed prostheses in sacral giant cell tumours and the clinical outcomes and complications at follow-up. METHODS: We retrospectively analyzed ten consecutive patients with giant cell tumors of the sacrum who underwent intralesional nerve-sparing resection with curative intent and custom implant reconstruction between 2016 and 2021. There were four males and six females with a mean age of 40.2 years (range, 25-62 years) at surgery. A computer-aided-design implant was prepared using 3D printing technology that was both matched to the bone defect and biomechanically evaluated. A 3D-printed surgical guide was used to replicate the resection procedure as planned. We analyzed operational outcomes, oncological outcomes, functional outcomes, complications, and prosthetic outcomes. Pain at rest was assessed according to a 10-cm VAS score. The results of functional improvement were evaluated using the MSTS-93 score at the final follow-up. RESULTS: All patients were observed for 26 to 61 months, with an average follow-up of 43.8 months. No deep infection or prosthetic structural failure occurred in this study. A total of 80% of patients had good neurological function and normal urinary, bowel, and ambulatory functions. The mean MSTS score was 24.1 (range, 22-26). The mean VAS score was 2 (range 0 to 2). Delayed wound healing occurred in three patients, and the wounds healed after debridement. One case had local recurrence and survived tumour-free after resection of the recurrent lesion. An aseptic loosening was found in a patient that did not require secondary surgery. By radiographical assessments, we found that 90% of implants were well osseointegrated at the final follow-up examination. CONCLUSIONS: The 3D-printed sacral implants might provide a promising strategy for spinopelvic reconstruction in sacral giant cell tumours undergoing intralesional nerve-sparing surgery with satisfactory clinical outcomes, osseointegration, and excellent durability.

Visible Light-Driven Conversion of Carbon-Sequestrated Seawater into Stoichiometric CO and HClO with Nitrogen-Doped BiOCl Atomic Layers.

Seawater is one of the most important CO2 sequestration media for delivering value-added chemicals/fuels and active chlorine; however, this scenario is plagued by sluggish reaction rates and poor product selectivity. Herein, we first report the synthesis of nitrogen-doped BiOCl atomic layers to directly split carbon-sequestrated natural seawater (Yellow Sea, China) into stoichiometric CO (92.8 µmol h-1 ) and HClO (83.2 µmol h-1 ) under visible light with selectivities greater than 90 %. Photoelectrons enriched on the exposed BiOCl{001} facet kinetically facilitate CO2 -to-CO reduction via surface-doped nitrogen bearing Lewis basicity. Photoholes, mainly located on the lateral facets of van der Waals gaps, promote the selective oxidation of Cl- into HClO. Sequestrated CO2 also maintains the pH of seawater at around 4.2 to prevent the alkaline earth cations from precipitating. The produced HClO can effectively kill typical bacteria in the ballast water of ocean-going cargo ships, offering a green and safe way for onsite sterilization.

Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial.

BACKGROUND: Thymic epithelial tumors (TETs) are rare malignancies and the treatment options are limited. We aimed to evaluate the efficacy and safety of apatinib, an angiogenesis inhibitor, in advanced TETs. METHODS: This was an open-label, single-arm, phase II trial at three centers in China. Patients with TET who had progressed after failure of at least one line of platinum-based chemotherapy were enrolled. Patients received apatinib 500 mg orally per day. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. RESULTS: From June 29, 2017, to April 18, 2019, 25 patients were enrolled. At data cut off (September 30, 2021), one patient achieved complete response, nine achieved partial response, and 11 achieved stable disease, with an ORR of 40% (95% CI 21-61%) and DCR of 84% (95% CI 64-95%). The median PFS was 9.0 (95% CI 5.4-12.6) months. The median OS was 24.0 (95% CI 8.2-39.8) months. All patients reported treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred 26 times in 15 patients. No grade 4 or 5 toxicities occurred. CONCLUSIONS: This is the first trial of apatinib for the treatment of TETs. Apatinib showed promising antitumor activity and the toxicities were tolerable and manageable.

Risk Stratification Based on Chronic Liver Failure Consortium Acute Decompensation Score in Patients With Child-Pugh B Cirrhosis and Acute Variceal Bleeding.

BACKGROUND AND AIMS: Optimal candidates for early transjugular intrahepatic portosystemic shunt (TIPS) in patients with Child-Pugh B cirrhosis and acute variceal bleeding (AVB) remain unclear. This study aimed to test the hypothesis that risk stratification using the Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) may be useful to identify a subgroup at high risk of mortality or further bleeding that may benefit from early TIPS in patients with Child-Pugh B cirrhosis and AVB. APPROACH AND RESULTS: We analyzed the pooled individual data from two previous studies of 608 patients with Child-Pugh B cirrhosis and AVB who received standard treatment between 2010 and 2017 in China. The concordance index values of CLIF-C ADs for 6-week and 1-year mortality (0.715 and 0.708) were significantly better than those of active bleeding at endoscopy (0.633 [P < 0.001] and 0.556 [P < 0.001]) and other prognostic models. With X-tile software identifying an optimal cutoff value, patients were categorized as low risk (CLIF-C ADs <48), intermediate risk (CLIF-C ADs 48-56), and high risk (CLIF-C ADs >56), with a 5.6%, 16.8%, and 25.4% risk of 6-week death, respectively. Nevertheless, the performance of CLIF-C ADs for predicting a composite endpoint of 6-week death or further bleeding was not satisfactory (area under the receiver operating characteristics curve [AUC], 0.588). A nomogram incorporating components of CLIF-C ADs and albumin, platelet, active bleeding, and ascites significantly improved the prediction accuracy (AUC, 0.725). CONCLUSIONS: In patients with Child-Pugh B cirrhosis and AVB, risk stratification using CLIF-C ADs identifies a subgroup with high risk of death that may derive survival benefit from early TIPS. With improved prediction accuracy for 6-week death or further bleeding, the data-driven nomogram may help to stratify patients in randomized trials. Future external validation of these findings in patients with different etiologies is required.

Temperature-insensitive optical sensors based on two cascaded identical microring resonators.

We demonstrate a novel, to the best of our knowledge, temperature-insensitive optical sensor based on two cascaded identical microring resonators (CIMRR) in this Letter. The structural parameters of the reference ring and sensing ring are designed to be identical. The upper cladding in the sensing windows of the two rings is removed. With different microfluidic channels, the reference ring and sensing ring are exposed to the reference solution and reagent sample, respectively. For wavelength interrogation experiments in the transmission spectrum contrast ratio and low-cost intensity interrogation experiments, the sensitivities of refractive index (RI) sensing are 3402.4 dB/RIU and 1087.3 dB/RIU, respectively, while the temperature sensitivities are as low as 0.023 dB/K and 0.0124 dB/K, respectively.

Genetic variability of E6 and E7 genes of human papillomavirus type 58 in Jingzhou, Hubei Province of central China.

BACKGROUND: Cervical cancer is a common malignant tumor in women, with a high mortality rate, has great harm to women's health. Long-term and persistent infection of high-risk human papillomavirus (HR-HPV) is the main reason of the occurrence and development of cervical cancer. METHODS: The infection rate of HPV-58 is higher in the Jingzhou area. In this study, 172 complete HPV-58 E6-E7 sequences were amplified by polymerase chain reaction (PCR), the amplified products were sequenced, and the gene variations of HPV-58 E6-E7 were analyzed. A Neighbor-Joining phylogenetic tree was constructed by MEGA 11. The secondary structure of E6 and E7 protein was investigated. PAML X was used to analyze the selective pressure. The B cell epitopes of E6 and E7 proteins in HPV-58 were predicted by ABCpred server. RESULTS: In E6 sequences, 10 single nucleotide variants were observed, including 7 synonymous and 3 non-synonymous variants. In E7 sequences, 12 single nucleotide variants were found, including 3 synonymous variants and 9 non-synonymous variants. There are 5 novel variants. The phylogenetic analysis showed that all the E6-E7 sequences were distributed in A lineage. No positively selected site was found in E6 sequence, but G63 in E7 sequences was identified as positively selected site. Some amino acid substitutions affected multiple B cell epitopes. CONCLUSION: Various E6 and E7 mutational data may prove useful for development of better diagnostic and vaccines for the region of Jingzhou, Hubei province of central China.

Oxygen and Chlorine Dual Vacancies Enable Photocatalytic O2 Dissociation into Monatomic Reactive Oxygen on BiOCl for Refractory Aromatic Pollutant Removal.

Room-temperature molecular oxygen (O2) dissociation is challenging toward chemical reactions due to its triplet ground-state and spin-forbidden characteristic. Herein, we demonstrate that BiOCl of oxygen and chlorine dual vacancies can photocatalytically dissociate O2 into monatomic reactive oxygen (•O-) for the ring opening of aromatic refractory pollutants toward deep oxidation. The electron-rich and geometry-flexible dual vacancies of oxygen and chlorine remarkably lengthen the O-O bond of adsorbed O2 from 1.21 to 2.74 Å, resulting in the rapid O2 dissociation and the subsequent •O- formation. During the photocatalytic degradation of sulfamethazine, the in situ-formed •O- plays an indispensable role in breaking the critical intermediate of pyrimidine containing a stubborn aromatic heterocyclic ring, thus facilitating the overall mineralization. More importantly, BiOCl of oxygen and chlorine dual vacancies is also superior to its monovacancy counterparts on the degradation of other refractory pollutants containing conjugated six-membered rings, including p-chlorophenol, p-chloronitrobenzene, p-hydroxybenzoic acid, and p-nitrobenzoic acid. This study sheds light on the importance of sophisticated defects for regulating the O2 activation manner and deliveries a novel O2 activation approach for environmental remediation with solar energy.

Surface Boronizing Can Weaken the Excitonic Effects of BiOBr Nanosheets for Efficient O2 Activation and Selective NO Oxidation under Visible Light Irradiation.

The photocatalytic O2 activation for pollutant removal highly depends on the controlled generation of desired reactive oxygen species (ROS). Herein, we demonstrate that the robust excitonic effect of BiOBr nanosheets, which is prototypical for singlet oxygen (1O2) production to partially oxidize NO into a more toxic intermediate NO2, can be weakened by surface boronizing via inducing a staggered band alignment from the surface to the bulk and simultaneously generating more surface oxygen vacancy (VO). The staggered band alignment destabilizes excitons and facilitates their dissociation into charge carriers, while surface VO traps electrons and efficiently activates O2 into a superoxide radical (•O2-) via a one-electron-transfer pathway. Different from 1O2, •O2- enables the complete oxidation of NO into nitrate with high selectivity that is more desirable for safe indoor NO remediation under visible light irradiation. This study provides a facile excitonic effect manipulating method for layered two-dimensional photocatalysts and sheds light on the importance of managing ROS production for efficient pollutant removal.

Predictive and prognostic impact of the different features of tumor budding in stage II colorectal cancer.

Tumor budding is a significant independent prognostic factor in colorectal cancer. Routine reporting of tumor budding is now advocated for in the colorectal cancer standard approach recommended by the International Tumor Budding Consensus Conference guidelines. However, the current tumor budding assessment system only emphasizes tumor budding quantity and ignores other features. Therefore, this study aimed to further determine the prognostic value of tumor budding based on a more comprehensive feature analysis. To this end, we conducted a retrospective pathology review of the different characteristics of tumor budding (that is quantity, structure, cell atypia, location, stromal reaction, and immunohistochemical phenotype) in 224 specimens of stage II colorectal cancer at our institution between 2009 and 2015. The mean age of the patients was 60.3±9.2 years (range, 39-84 years). Among various features of tumor budding, single-cell budding, anaplasia-like cell atypia, myxoid stroma, high tumor budding quantity, and loss of CDX2 expression were independent predictors of recurrence and mortality in patients with stage II colorectal cancer. Based on these results, we suggest that in addition to tumor-budding quantity, other tumor budding features play important biological roles in the development of colorectal cancer. Our findings provide prognostic information that could help with guiding clinical management and oncology care models for patients with stage II colorectal cancer.

The potential mechanism of Chebulae Fructus in the treatment of hepatocellular carcinoma on the basis of network pharmacology.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) ranks third on the list of the leading cause for cancer death globally. The treatment of HCC patients is unsatisfactory. However, the traditional Chinese medicine Chebulae Fructus has potential efficacy in the treatment of HCC. MATERIALS AND METHODS: We mined the active ingredients of Chebulae Fructus and its main targets from the Traditional Chinese Medicine Systems Pharmacology database. HCC-related datasets were downloaded from The Cancer Genome Atlas database and differentially expressed genes (DEGs) in HCC were obtained by differential expression analysis. Top10 small molecule compounds capable of reversing HCC pathology were screened by the Connectivity Map database based on DEGs. Ellipticine, an extract of Chebulae Fructus, had the potential to reverse HCC pathology. Protein-Protein Interaction (PPI) networks of DEGs in HCC were constructed using STRING. Eighteen potential targets of Chebulae Fructus for the treatment of HCC were obtained by taking intersection of DEGs in HCC with targets corresponding to the active constituents of Chebulae Fructus. In addition, MTT assay was also employed to examine the effect of ellipticine on HCC cell viability. RESULTS: It has been shown that ellipticine and ellagic acid have antitumor activity. Random Walk with Restart analysis of PPI networks was performed using potential targets as seeds, and the genes with the top 50 affinity coefficients were selected to construct a drug-active constituent-gene interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key genes involved in the treatment of HCC with Chebulae Fructus demonstrated that these genes were mainly enriched in signaling pathways related to tumor metabolism such as cAMP signaling pathway and Ras signaling pathway. Finally, it was verified by MTT assay that proliferation of HCC cells could be remarkably hindered. CONCLUSIONS: We excavated ellipticine, a key active constituent of Chebulae Fructus, by network pharmacology, and elucidated the signaling pathways involved in Chebulae Fructus, providing a theoretical basis for the use of Chebulae Fructus for HCC clinical application.

Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study.

BACKGROUND: Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients. METHODS: Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival. DISCUSSION: The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030. TRIAL REGISTRATION: clinicaltrials.gov, NCT04636593 . Registered 19 November 2020 - Retrospectively registered.