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Objective: Large volume radiological text data have been accumulated since the incorporation of electronic health record (EHR) systems in clinical practice. We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis. Methods: Sonographic EHR data were obtained from the EHR database. Pathological reports were used as the gold standard for diagnosing thyroid cancer. We developed thyroid cancer diagnosis based on natural language processing (THCaDxNLP) to interpret unstructured sonographic text reports for thyroid cancer diagnosis. We used the area under the receiver operating characteristic curve (AUROC) as the primary metric to measure the performance of the THCaDxNLP. We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs. those without THCaDxNLP using 5 independent test sets. Results: We obtained a total number of 788,129 sonographic radiological reports. The number of thyroid sonographic data points was 132,277, 18,400 of which were thyroid cancer patients. Among the 5 test sets, the numbers of patients per set were 439, 186, 82, 343, and 171. THCaDxNLP achieved high performance in identifying thyroid cancer patients (the AUROC ranged from 0.857–0.932). Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy (93.8% vs. 87.2%; one-sided t-test, adjusted P = 0.003), precision (92.5% vs. 86.0%; P = 0.018), and F1 metric (94.2% vs. 86.4%; P = 0.007). Conclusions: THCaDxNLP achieved a high AUROC for the identification of thyroid cancer, and improved the accuracy, sensitivity, and precision of thyroid ultrasound radiologists. This warrants further investigation of THCaDxNLP in prospective clinical trials.

Breast mass is one of the clinical signs of breast lesions. Clinically, breast tumors can occur in breast cancer, breast tuberculosis, breast duct dilatation, breast cysts, breast fibroadenoma, and breast hyperplasia. Its pathogenesis is not clear. The occurrence of breast lesions is related to many factors, such as diet, trauma, genetic mutations, inheritance, endocrine disorders, breast development, and chronic stimuli. With the continuous improvement of examination equipment and continuous improvement of the treatment level, the incidence of breast masses is increasing. For a long time, clinicians have mostly used hand palpation methods to complete the diagnosis of breast masses based on the relatively hard properties of breast masses and adjacent tissues. It is more difficult to diagnose patients based on their clinical symptoms and signs, and it is easy to miss the diagnosis. Choosing the appropriate diagnostic method to confirm breast mass disease has become the first task for the diagnosis and treatment of breast mass. Ultrasound elastography is a new ultrasound examination method. It diagnoses the elasticity and hardness of breast masses by using corresponding characteristics. The imaging principle is to apply pressure to the tissue at the lesion site to determine its elasticity and hardness to identify the nature of the tumor. This article explores the clinical value of ultrasound elastography in the effective diagnosis of breast masses. Compared with the diagnosis results of ordinary ultrasound, the parameters such as the position, shape, size, boundary, internal echo, and rear echo of the focused mass were observed. Facts have proved that elastography can be used to make a qualitative differential diagnosis of benign and malignant breast masses from another angle according to the different characteristics of the hardness of the tissue being examined. It is non-invasive, non-radiative, low-cost, and easy for patients to accept. Provide valuable clinical diagnosis basis for early detection and treatment of breast masses.

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.Patients and methodsMetastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.ResultsFifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.ConclusionsSerological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy.

Hashimoto’s thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836–0.939) and 0.895 (0.862–0.927). HTNet exceeds radiologists’ performance on accuracy (83.2% versus 79.8%; binomial test, p p p = 0.004) and static-image (AUC, 0.914 versus 0.901; p = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.

We studied the characteristics of contrast-enhanced ultrasound (CEUS) in renal pelvic urothelial carcinomas and explored its performance in assessing microvessel density (MVD) of tumor tissues. We retrospectively analyzed the characteristics of 125 cases, which were confirmed pathologically to be renal pelvic urothelial carcinomas using CEUS. We performed CEUS and found that most tumors presented with an enhanced mode of "slow-in (mean = 16.7 ± 2.6 s, range: 12-25 s), hypo-enhancement and fast-out (mean = 69.3 ± 16.2 s, range: 42-113 s)." However, the wash-in pattern, homogeneity and wash-out pattern observed with CEUS was not correlated with pT stage and grade (p0.05). But advanced-pT-stage and high-grade tumors had a higher peak enhancement than early-pT-stage and low-grade tumors (p0.01). Peak enhancement obtained with CEUS can be used to evaluate the pT stage and grade of renal pelvic urothelial carcinomas more effectively. The MVD of those tissues was observed using immunohistochemical staining of cluster of differentiation 34 (CD34). MVD in the advanced-pT-stage and high-grade groups was significantly higher than that in the early-pT-stage and low-grade groups (p0.01). As tumor pT stage and grade improved, CEUS peak enhancement intensity and MVD of tumors also exhibited an upward trend. CEUS peak enhancement intensity has the potential to determine MVD of renal pelvic urothelial carcinomas.

To compare the gut microbiota of healthy infants based on specific interactions of delivery modes and feeding types, we recruited 62 healthy babies who were followed up for 2 years from our previous cohort study of 91 infants (the rest were lost to follow-up). They were exclusively fed breast milk or specific formulas for more than 4 months after birth. The fecal bacterial composition was tested at 40 days, 3 months, and 6 months of age. Solid foods were introduced from 4 to 6 months of age and thus did not affect the microbiota before 4 months of age. According to the different delivery modes (i.e., vaginal delivery, VD, or cesarean section delivery, CS) and feeding types (i.e., breast-fed, br, or formula-fed, fo), the infants were assigned to four different groups, namely, the VD-br, VD-fo, CS-br, and CS-fo groups. We found that at 40 days of age, the α diversity (reported as the Shannon index) was lower in the br infants than in the fo infants. At 3 months of age, the α diversity was significantly lower in the CS-br group, although significant differences were not observed after solid food introduction. Bifidobacterium represented the most predominant genus in all groups at all time points, followed by Enterobacteriaceae. At 40 days of age, the abundance of Bifidobacterium was much higher in the CS-br group than in the CS-fo group but did not differ between the VD-br and VD-fo groups. The differences in Bifidobacterium disappeared at 3 and 6 months of age among the different groups. At 40 days of age, the abundance of Streptococcus and Enterococcus was much lower in the br infants than in the CS-fo group. At 3 months of age, Enterococcus was significantly lower in the CS-br group than in the fo infants, although for infants delivered by VD, the difference between feeding types was not significant. The specific interaction of delivery modes and feeding types has a large impact on the infants' gut microbiota. Breastfeeding and VD may decrease the potential adverse effects of formula feeding or CS delivery on gut microbiota, thus leading to a more stable and beneficial gut environment for infants.

As a result of thrombosis or intimal hyperplasia, synthetic artificial vascular grafts had a low success rate when they were used to replace small-diameter arteries (inner diameterlt; 6 mm). C-type natriuretic peptides (CNP) have anti-thrombotic effects, and can promote endothelial cell (EC) proliferation and inhibit vascular smooth muscle cell (SMC) over-growth. In this study, poly(ε-caprolactone) (PCL) vascular grafts loaded with CNP (PCL-CNP) were constructed by electrospinning. The PCL-CNP grafts were able to continuously release CNP at least 25 days in vitro. The results of scanning electron microscopy (SEM) and mechanical testing showed that the loading of CNP did not change the microstructure and mechanical properties of the PCL grafts. In vitro blood compatibility analysis displayed that PCL-CNP grafts could inhibit thrombin activity and reduce platelet adhesion and activation. In vitro cell experiments demonstrated that PCL-CNP grafts activated ERK1/2 and Akt signaling in human umbilical vein endothelial cells (HUVECs), as well as increased cyclin D1 expression, enhanced proliferation and migration, and increased vascular endothelial growth factor (VEGF) secretion and nitric oxide (NO) production. The rabbit arteriovenous (AV)-shunt ex vitro indicated that CNP loading significantly improved the antithrombogenicity of PCL grafts. The assessment of vascular grafts in rat abdominal aorta implantation model displayed that PCL-CNP grafts promoted the regeneration of ECs and contractile SMCs, modulated macrophage polarization toward M2 phenotype, and enhanced extracellular matrix remodeling. These findings confirmed for the first time that loading CNP is an effective approach to improve the hemocompatibility and vascular regeneration of synthetic vascular grafts. STATEMENT OF SIGNIFICANCE: Small-diameter (lt; 6 mm) vascular grafts (SDVGs) have not been made clinically available due to their prevalence of thrombosis, limited endothelial regeneration and intimal hyperplasia. The incorporation of bioactive molecules into SDVGs serves as an effective solution to improve hemocompatibility and endothelialization. In this study, for the first time, we loaded C-type natriuretic peptides (CNP) into PCL grafts by electrospunning and confirmed the effectiveness of loading CNP on improving the hemocompatibility and vascular regeneration of artificial vascular grafts. Regenerative advantages included enhancement of endothelialization, modulation of macrophage polarization toward M2 phenotypes, and improved contractile smooth muscle cell regeneration. Our investigation brings attention to CNP as a valuable bioactive molecule for modifying cardiovascular biomaterial.

OBJECTIVE: To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex. METHODS: A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes. RESULTS: Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils (P

Objective: Immune checkpoint inhibitors (ICIs) have achieved remarkable results in cancer treatments. However, there is no effectivepredictive biomarker for gastrointestinal (GI) cancer. Methods: We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the MemorialSloan Kettering Cancer Center cohort (MSK-GI, n = 227), the Janjigian cohort (n = 40), and the Peking University Cancer Hospital& Institute cohort (PUCH, n = 80) to determine the possible associations between DNA damage response and repair (DDR) genemutations and clinical outcomes. Data from The Cancer Genome Atlas database were analyzed to determine the possible correlationsbetween DDR gene mutations and the tumor microenvironment. Results: In the MSK cohort, the presence of ≥ 2 DDR gene mutations was correlated with prolonged overall survival (OS). TheJanjigian and PUCH cohorts further confirmed that subgroups with ≥ 2 DDR gene mutations displayed a prolonged OS and ahigher durable clinical benefit. Furthermore, the DDR gene mutation load could be considered as an independent prognostic factor,and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs. Mechanistically, we showed that thepresence of ≥ 2 DDR gene mutations was correlated with higher levels of tumor mutation burden, neoantigen, and T cell infiltration. Conclusions: The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs,which could serve as a potential biomarker to guide patient selection for immunotherapy.

In the current study, two similar substituted imidazo[1,2-α]pyridine ligands with different coordination groups were facilely synthesized, and were further used for construction of two novel Cu(II)...

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy.

With the expanding use of immune checkpoint inhibitors (ICIs) in gastrointestinal (GI) cancer, the occurrence of acquired resistance (AR) has gradually emerged. However, the progression patterns and survival of patients with AR to ICIs are still unknown.To explore the characteristics and prognosis of AR after ICI therapy in patients with advanced GI cancer.This cohort study screened patients with advanced GI cancer treated with ICIs between January 14, 2016, and December 31, 2020, at Peking University Cancer Hospital. Initial response was defined as complete response, partial response, or stable disease longer than 6 months as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Progression was also based on Response Evaluation Criteria in Solid Tumors version 1.1. Progression or death after the initial response was defined as AR. Oligoprogression of AR was defined as 2 or more disease sites progression. The current status of AR in GI cancer and the patterns of AR and its prognosis were evaluated. The site of AR and subsequent management were also assessed. Data were analyzed from June to August 2021.Patients in the cohort were treated with mono-ICI or combination therapy.Kaplan-Meier analyses and log-rank tests were conducted for overall survival analyses. Univariate and multivariate Cox analyses were conducted to determine the prognostic implications of each variable.Of the 1124 patients who received ICIs, 373 (33.2%) patients (282 men [75.6%]; median [IQR] age, 62 [54-68] years) achieved an initial response, and 173 (46.4%) patients (137 men [79.2%]; median [IQR] age, 61 [54-67] years) developed AR. Almost all patients (167 patients [96.5%]) developed AR within 24.0 months. Progression patterns of AR were most commonly oligoprogression (122 patients [70.5%]) rather than polymetastatic progression (38 patients [22.0%]) and were associated with a good prognosis (38.5 vs 14.0 months; hazard ratio, 0.37; 95% CI, 0.18-0.74; P .001). Lymph nodes (101 patients [58.4%]) appeared to be the most common site of AR. Management after AR was mainly systemic therapy (96 patients [55.5%]).Oligoprogression was the most common pattern of AR progression, and lymph nodes were the most susceptible site for AR. Further study will be needed to determine the most favorable management for AR.

Introduction Multimodal imaging agent has the potential to overcome the shortage and incorporate the advantages of different imaging tools for extremely sensitive diagnosis. To achieve multimodal imaging, combining multiple contrast agents into a special nanostructure has become a main strategy; However, the combination of all of these functions into one nanoplatform usually requires a complicated synthetic procedure that results in heterogeneous nanostructure. Methods In this study, we develop ultrasmall gold nanoclusters with 15 gold atoms (Au15NCs) functionalized with diethylenetriamine-pentaacetic acid dianhydride (DTPAA-Gd) as an optimized multimodal imaging agent to enhance imaging ability. Results The Au15NCs-DTPAA-Gd nanohybrids possess the ultra-small size and are capable of enhancing the contrast in near-infrared fluorescence (NIRF), magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Meanwhile, the integrated DTPAA-Gd component not only endow the nanohybrids to produce higher T1 relaxivity (r1 = 21.4 mM−1 s−1) than Omnipaque (r1 = 3.973 mM−1s−1) but also further enhance X-ray attenuation property of Au15NCs. Importantly, the fluorescence intensity of Au15NCs-DTPAA-Gd did not decrease compared with Au15NCs. Ultimately, in vivo imaging experiments have demonstrated that Au15NCs-DTPAA-Gd nanohybrids can be quickly eliminated from the body through the urinary system and has great potential for anatomical imaging. Conclusion These data manifest Au15NCs-DTPAA-Gd present great potential as a multimodal contrast agent for disease diagnosis, especially for early accurate detection of tumors.

Plant–plant interactions change in response to environmental conditions, and riparian species are commonly influenced by flooding. This study tested whether flooding affects the intraspecific and interspecific competition of two riparian species and whether such effects depend on the topographic positions where plants have established. Seeds of the riparian species Polygonum hydropiper were collected from both low and high positions within the shoreline of the Three Gorges Reservoir. Groups of P. hydropiper seedlings from each position were either grown alone (i.e., without competition), with another group of P. hydropiper seedlings (i.e., intraspecific competition), or with a group of seedlings of the companion species Xanthium sibiricum (i.e., interspecific competition). Each group comprised six replicates. In total, 288 plants of P. hydropiper and 84 plants of X. sibiricum were selected for the experiment. Seedlings were subjected to control and flooding treatments for 60 days. Irrespective of competition type (i.e., intra- or interspecific), both flooding and competition negatively affected the growth and/or photosynthetic capacities of P. hydropiper. Flooding only interacted with competition to explain total biomass. Flooding reduced total biomass in a larger proportion in the absence of competition, and, to a lesser extent, with intraspecific competition, compared to interspecific competition. However, such interaction effects were independent of the positions where the seeds that originated from the plants were collected from. Interspecific competition significantly decreased the chlorophyll content and photosynthetic efficiency of plants, while intraspecific competition did not. In general, plants from lower positions had higher total chlorophyll content than plants from higher positions. These results suggest that flooding may regulate the population dynamics of P. hydropiper by altering its competitive interactions.

Beet necrotic yellow vein virus (BNYVV) is a serious threat to the sugar beet industry worldwide. However, little information is available regarding the genetic diversity and population structure of BNYVV in China. Here, we analyzed multiple sequences from four genomic regions (CP, RNA3, RNA4 and RNA5) of a set of Chinese isolates. Sequence analyses revealed that several isolates were mixed infections of variants with different genotypes and/or different p25 tetrad motifs. In total, 12 distinct p25 tetrads were found in the Chinese BNYVV population, of which four tetrads were newly identified. Phylogenetic analyses based on four genes (CP, RNA3-p25, RNA4-p31 and RNA5-p26) in isolates from around the world revealed the existence of two to four groups, which mostly corresponded to previously reported phylogenetic groups. Two new subgroups and a new group were identified from the Chinese isolates in p25 and p26 trees, respectively. Selection pressure analysis indicated that there was a positive selection pressure on the p25 from the Chinese isolates, but the other three proteins were under a negative selection pressure. There was frequent gene flow between geographically distant populations, which meant that BNYVV populations from different provinces were not geographically differentiated.

Grapevine leafroll-associated virus 3 (GLRaV-3) is the most prevalent causal agent of grapevine leafroll disease (GLD). Of the 75 grapevine samples collected from three regions in China, 46.7% and 94.7% of samples tested positive for GLRaV-3 in reverse transcription-PCR (RT-PCR) and reverse transcription nested PCR (RT-nPCR), respectively. The SSCP analysis for the clones of complete CP gene from 16 GLRaV-3 isolates showed that 15 isolates contained one predominant haplotype and one isolate had no predominant haplotype. The sequences of the CP genes showed 89.9–100% identities at the nucleotide level. Phylogenetic analysis of the CP gene sequences revealed the existence of four well defined variant groups, which corresponded to previously reported phylogenetic groups (1, 2, 3, and 5). Two new sub-groups designated as sub-group 1B and sub-group 3B in groups 1 and 3, respectively, were identified in the Chinese GLRaV-3 population. Recombination analyses illustrated that those two new sub-groups (1B and 3B) were emerged as a result of recombination events between variants in groups 1 and 2, and variants in groups 1 and 3, respectively. These results further indicated that the variants in those new sub-groups are viable and evolutionary successful. Recombinants with highly similar coat protein structure to variants of group 1 were abundantly found in the viral population. In addition, these analyses provided evidence about CP gene as one of the recombination hotspots in GLRaV-3 genome. The population genetic parameters of all available CP sequences suggested that the recombinants might have emerged due to population bottlenecks during transmission. The results provide new insights into the variability and evolution of GLRaV-3.

The special geographical location Russia lies in creates the unique character of the Russian nation. Based on the dual nature of the Russian national character, the Russian geographical environment and the analysis of its social structure, this text tries to explore the reasons of the dual nature of Russian national character.