A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy.

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.

Association between polymorphisms and atopic dermatitis susceptibility: A systematic review and meta-analysis.

AIM: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that is closely linked to genetic factors. Previous studies have revealed numerous single nucleotide polymorphisms (SNPs) that been related to susceptibility to AD; however, the results are conflicting. Therefore, a meta-analysis was conducted to assess the associations of these polymorphisms and AD risk. MATERIAL AND METHODS: PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were retrieved to identify eligible studies, with selected polymorphisms being reported in a minimum of three separate studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality. Review Manager 5.3 and STATA 14.0 were used to perform the meta-analysis. RESULTS: After screening, 64 studies involving 13 genes (24 SNPs) were selected for inclusion in the meta-analysis. Nine SNPs were positively correlated with AD susceptibility [filaggrin (FLG) R501X, FLG 2282del4, chromosome 11q13.5 rs7927894, interleukin (IL)-17A rs2275913, IL-18 -137 G/C, Toll-like receptor 2 (TLR2) rs5743708, TLR2 A-16934 T, serine protease inhibitor Kazal type-5 (SPINK5) Asn368Ser, interferon-γ (IFN-γ) T874A] and one was negatively associated with AD susceptibility (IL-4 -1098 T/G). The 14 remaining SNPs were not significantly associated with AD susceptibility. CONCLUSIONS: Nine SNPs that may be risk factors and one SNP that may be a protective factor for AD were identified, providing a reference for AD prediction, prevention, and therapy.

Association of asthma and lung cancer risk: A pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Over the past 2 decades, population-based studies have shown an increased association between asthma and the risk of lung cancer. However, the causal links between these 2 conditions remain poorly understood. METHODS: We conducted a comprehensive search of various databases, including PubMed, Embase, Web of Science, and Cochrane Library, up until May 04, 2023. Only articles published in English were included in our study. We performed a meta-analysis using random-effects models to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI). Subgroup analyses were conducted based on study design, gender, and histologic types. We also conducted a 2-sample Mendelian randomization (MR) using the genome-wide association study pooled data (408,422 people) published by the UK Biobank to explore further the potential causal relationship between asthma and lung cancer. RESULTS: Our meta-analysis reviewed 24 population-based cohort studies involving 1072,502 patients, revealing that asthma is significantly associated with an increased risk of lung cancer (OR = 1.29, 95% CI 1.19-1.38) in all individuals. Subgroup analysis showed a significantly higher risk of lung cancer in females with asthma (OR = 1.23, 95% CI 1.01-1.49). We found no significant association between asthma and lung adenocarcinoma (LUAD) (OR = 0.76, 95% CI 0.54-1.05), lung squamous carcinomas (LUSC) (OR = 1.09, 95% CI 0.79-1.50), or small-cell lung cancer (SCLC) (OR = 1.00, 95% CI 0.68-1.49). Interestingly, our MR analysis supported an increasing causality between asthma and lung cancer (OR = 1.11, 95% CI 1.04-1.17, P = .0008), specifically in those who ever smoker (OR = 1.09, 95% CI 1.01-1.16, P = .0173) and LUSC pathological type (OR = 1.15, 95% CI 1.05-1.26, P = .0038). CONCLUSION: Through meta-analysis, our study confirms that patients with asthma have a higher risk of developing lung cancer. Our MR study further support an increasing causal relationship between asthma and the risk of lung cancer, particularly in smokers and LUSC. Future studies examining the link between asthma and the risk of developing lung cancer should consider the bias of controlled and uncontrolled asthma.

IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes.

Investigating correlations between radiomic and genomic profiling in breast cancer (BC) molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment. We present a well-designed radiogenomic framework image-gene-gene set (IMAGGS), which detects multi-way associations in BC subtypes by integrating radiomic and genomic features. Our dataset consists of 721 patients, each of whom has 12 ultrasound (US) images captured from different angles and gene mutation data. To better characterize tumor traits, 12 multi-angle US images are fused using two distinct strategies. Then, we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm, deviating from the prevalent one-to-one relationship pattern observed in previous studies. Key radiomic and genomic features are screened using these associations. In addition, gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC subtypes. We further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and diseases. Taken together, IMAGGS provides a comprehensive characterization for diseases by associating imaging, genes, and gene sets, paving the way for biological interpretation of radiomics and development of targeted therapy.

Histone deacetylase 3 inhibition alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis via epigenetically upregulating Nrf2/HO-1 signaling pathway.

Atopic dermatitis (AD) is a frequent skin disorder that is associated with immune dysfunction and skin inflammation. Histone deacetylase 3 (HDAC3) possesses strong immune and inflammatory modulatory properties in multiple diseases. However, the role and mechanism of HDAC3 in AD remain unknown. Here, we reported that HDAC3 expression was aberrantly upregulated in 2,4-dinitrochlorobenzene (DNCB)-induced lesional AD skin in mice. Inhibition of HDAC3 by RGFP966 protected against DNCB-induced AD, indicated by improved histological damages, relieved inflammatory and immune dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway activity in lesional AD skin was significantly decreased and RGFP966 attenuated the decrease. Inhibition of Nrf2/HO-1 signaling pathway via Nrf2 inhibitor ML385 blunted anti-AD effect of RGFP966 in DNCB-treated mice. Mechanistically, RGFP966 promoted Nrf2 expression and upregulated H3K27ac deposition on the promoter region of Nrf2. Collectively, HDAC3 inhibition protects against AD via epigenetically activating Nrf2 transcription to upregulate Nrf2/HO-1 signaling pathway activity. HDAC3 may act as a promising therapeutic target for the treatment of AD.

Sodium Butyrate Ameliorates Atopic Dermatitis-Induced Inflammation by Inhibiting HDAC3-Mediated STAT1 and NF-κB Pathway.

A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid breakdown by the gut microbiota, have been widely reported in numerous inflammatory diseases. However, the effect of NaB treatment alone on AD has not been reported. In the current study, AD was induced in BALB/c mice with 2,4-dinitrochlorobenzene (DNCB) for 28 days with NaB (200 mg/kg) treatment by gavage. NaB attenuated AD-induced skin bleeding, scarring, dryness, abrasions and erosions. In addition, NaB inhibited inflammatory cells infiltration and attenuated the expression of inflammatory cytokines and chemokines. Mechanistically, NaB reduced histone deacetylase 3 (HDAC3) expression and NF-κB p65 nuclear translocation by increasing the lysine acetylation levels of STAT1 and NF-κB p65 in AD. Taken together, our study suggests that NaB inhibits inflammatory mediators and ameliorates AD by inhibiting HDAC3 expression, thereby upregulating STAT1 and NF-κB p65 lysine acetylation levels and reducing NF-κB p65 nuclear translocation. Therefore, this study provides a new theoretical basis for NaB in the treatment of AD.

Research progress on pathogenic and therapeutic mechanisms of Enterovirus A71.

In recent years, enterovirus A71 (EV-A71) infection has become a major global public health problem, especially for infants and young children. The results of epidemiological research show that EV-A71 infection can cause acute hand, foot, and mouth disease (HFMD) and complications of the nervous system in severe cases, including aseptic pediatric meningoencephalitis, acute flaccid paralysis, and even death. Many studies have demonstrated that EV-A71 infection may trigger a variety of intercellular and intracellular signaling pathways, which are interconnected to form a network that leads to the innate immune response, immune escape, inflammation, and apoptosis in the host. This article aims to provide an overview of the possible mechanisms underlying infection, signaling pathway activation, the immune response, immune evasion, apoptosis, and the inflammatory response caused by EV-A71 infection and an overview of potential therapeutic strategies against EV-A71 infection to better understand the pathogenesis of EV-A71 and to aid in the development of antiviral drugs and vaccines.

Unraveling the Pivotal Network of Ultrasound and Somatic Mutations in Triple-Negative and Non-Triple-Negative Breast Cancer.

Purpose: The emergence of genomic targeted therapy has improved the prospects of treatment for breast cancer (BC). However, genetic testing relies on invasive and sophisticated procedures. Patients and Methods: Here, we performed ultrasound (US) and target sequencing to unravel the possible association between US radiomics features and somatic mutations in TNBC (n=83) and non-TNBC (n=83) patients. Least absolute shrinkage and selection operator (Lasso) were utilized to perform radiomic feature selection. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was utilized to identify the signaling pathways associated with radiomic features. Results: Thirteen differently represented radiomic features were identified in TNBC and non-TNBC, including tumor shape, textual, and intensity features. The US radiomic-gene pairs were differently exhibited between TNBC and non-TNBC. Further investigation with KEGG verified radiomic-pathway (ie, JAK-STAT, MAPK, Ras, Wnt, microRNAs in cancer, PI3K-Akt) associations in TNBC and non-TNBC. Conclusion: The pivotal network provided the connections of US radiogenomic signature and target sequencing for non-invasive genetic assessment of precise BC treatment.

Modification of size cutoff for biopsy based on the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) for thyroid nodules in patients younger than 19 years.

OBJECTIVES: To modify the size cutoff for biopsy for thyroid nodules in patients < 19 years based on the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and evaluate the performance of the new criteria in two referral centers. METHODS: Patients < 19 years with cytopathologic or surgical pathology results were retrospectively identified from two centers from May 2005 to August 2022. Patients from one center were classified as the training cohort, and those from the other center were classified as the validation cohort. The diagnostic performance, unnecessary biopsy rates, and missed malignancy rates of the TI-RADS guideline, and the new criteria (≥ 35 mm for TR3 and no threshold for TR5) were compared. RESULTS: A total of 236 nodules from 204 patients in the training cohort and 225 nodules from 190 patients in the validation cohort were analyzed. The area under the receiver operating characteristic curve of the new criteria in identifying thyroid malignant nodules was higher (0.809 vs. 0.681, p < 0.001; 0.819 vs. 0.683, p < 0.001), and the unnecessary biopsy rates (45.0% vs. 56.8%; 42.2% vs. 56.8%) and missed malignancy rates (5.7% vs. 18.6%; 9.2% vs. 21.5%) were lower than that of the TI-RADS guideline in the training cohort and validation cohort, respectively. CONCLUSIONS: The new criteria (≥ 35 mm for TR3 and no threshold for TR5) for biopsy based on the TI-RADS may help improve the diagnostic performance and reduce unnecessary biopsy rates and missed malignancy rates for thyroid nodules in patients < 19 years. CLINICAL RELEVANCE STATEMENT: The study developed and validated the new criteria (≥ 35 mm for TR3 and no threshold for TR5) to indicate FNA based on the ACR TI-RADS of thyroid nodules in patients younger than 19 years. KEY POINTS: •The AUC of the new criteria (≥ 35 mm for TR3 and no threshold for TR5) in identifying thyroid malignant nodules was higher than that of the TI-RADS guideline (0.809 vs. 0.681) in patients < 19 years. •The unnecessary biopsy rates and missed malignancy rates of the new criteria (≥ 35 mm for TR3 and no threshold for TR5) in identifying thyroid malignant nodules were lower than that of the TI-RADS guideline in patients < 19 years (45.0% vs. 56.8% and 5.7% vs. 18.6%, respectively).

Deep learning radiomics model based on breast ultrasound video to predict HER2 expression status.

Purpose: The detection of human epidermal growth factor receptor 2 (HER2) expression status is essential to determining the chemotherapy regimen for breast cancer patients and to improving their prognosis. We developed a deep learning radiomics (DLR) model combining time-frequency domain features of ultrasound (US) video of breast lesions with clinical parameters for predicting HER2 expression status. Patients and Methods: Data for this research was obtained from 807 breast cancer patients who visited from February 2019 to July 2020. Ultimately, 445 patients were included in the study. Pre-operative breast ultrasound examination videos were collected and split into a training set and a test set. Building a training set of DLR models combining time-frequency domain features and clinical features of ultrasound video of breast lesions based on the training set data to predict HER2 expression status. Test the performance of the model using test set data. The final models integrated with different classifiers are compared, and the best performing model is finally selected. Results: The best diagnostic performance in predicting HER2 expression status is provided by an Extreme Gradient Boosting (XGBoost)-based time-frequency domain feature classifier combined with a logistic regression (LR)-based clinical parameter classifier of clinical parameters combined DLR, particularly with a high specificity of 0.917. The area under the receiver operating characteristic curve (AUC) for the test cohort was 0.810. Conclusion: Our study provides a non-invasive imaging biomarker to predict HER2 expression status in breast cancer patients.

Evaluation of the role of postoperative radiotherapy in locally invasive thymoma: A propensity-matched study based on the SEER database.

OBJECTIVES: No consensus was reached on the efficacy of postoperative radiotherapy (PORT) in locally invasive thymomas because of the rarity of the thymic epithelial and the variations of study results. Therefore, we aimed to explore the efficacy of PORT in locally invasive thymomas using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with thymomas from 2004 to 2016 were identified using the SEER database. Prognostic factors of cancer-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses.Propensity score matching (PSM) was performed to balance the baseline characteristics. RESULTS: A total of 700 eligible patients were identified. After PSM, 262 paired patients were selected from the two groups, those who received or did not receive PORT. Receiving PORT improved CSS and OS before and after PSM. In the matched population, the multivariate analyses showed that tumour invasion into adjacent organs/structures and non-utilisation of PORT were independent poor prognostic factors for CSS, whereas age ≥62 years,tumour invasion into adjacent organs/structures, and non-utilisation of PORT were independently associated with poorer OS. The subgroup analysis revealed that PORT improved CSS and OS in Masaoka-Koga stage III thymoma, but showed no OS benefit in Masaoka-Koga stage IIB thymoma. CONCLUSION: Based on the SEER database, we found that PORT provides a significant survival benefit in Masaoka-Koga stage III thymoma with complete or incomplete resection. The role of PORT in thymoma requires further evaluation.

Virtual elastography ultrasound via generative adversarial network for breast cancer diagnosis.

Elastography ultrasound (EUS) imaging is a vital ultrasound imaging modality. The current use of EUS faces many challenges, such as vulnerability to subjective manipulation, echo signal attenuation, and unknown risks of elastic pressure in certain delicate tissues. The hardware requirement of EUS also hinders the trend of miniaturization of ultrasound equipment. Here we show a cost-efficient solution by designing a deep neural network to synthesize virtual EUS (V-EUS) from conventional B-mode images. A total of 4580 breast tumor cases were collected from 15 medical centers, including a main cohort with 2501 cases for model establishment, an external dataset with 1730 cases and a portable dataset with 349 cases for testing. In the task of differentiating benign and malignant breast tumors, there is no significant difference between V-EUS and real EUS on high-end ultrasound, while the diagnostic performance of pocket-sized ultrasound can be improved by about 5% after V-EUS is equipped.

Glutamate-cysteine ligase catalytic and its modifier function as novel immunotargets in gastric adenocarcinoma.

OBJECTIVES: To determine the expression and function of glutamate-cysteine ligase catalytic (GCLC) and glutamate-cysteine ligase catalytic modifier (GCLM) in gastric adenocarcinoma. METHODS: Bioinformatics was used to analyze the expression of GCLC and GCLM. We download and analyzed the expression of gastric adenocarcinoma patients from TCGA database. Moreover, the method of immunochemistry was used to verify the expression of GCLC and GCLM in gastric adenocarcinoma. RESULTS: At first, the expression of GCLC and GCLM in gastric adenocarcinoma tissues were both significantly higher compared with normal tissues analyzed via TCGA database. Then, gastric adenocarcinoma tissues were collected and performed with immunochemistry. The gastric adenocarcinoma with positive staining for GCLC and GCLM was 77% and 80%, respectively, which was significantly higher compared with adjacent normal tissues (9% and 11%, respectively). CONCLUSIONS: The disordered expression of GCLC and GCLM in gastric adenocarcinoma suggested that these factors may induce tumorigenesis and may be a novel target for diagnosis and treatment of gastric adenocarcinoma.

Identification of Heat-Tolerant Genes in Non-Reference Sequences in Rice by Integrating Pan-Genome, Transcriptomics, and QTLs.

The availability of large-scale genomic data resources makes it very convenient to mine and analyze genes that are related to important agricultural traits in rice. Pan-genomes have been constructed to provide insight into the genome diversity and functionality of different plants, which can be used in genome-assisted crop improvement. Thus, a pan-genome comprising all genetic elements is crucial for comprehensive variation study among the heat-resistant and -susceptible rice varieties. In this study, a rice pan-genome was firstly constructed by using 45 heat-tolerant and 15 heat-sensitive rice varieties. A total of 38,998 pan-genome genes were identified, including 37,859 genes in the reference and 1141 in the non-reference contigs. Genomic variation analysis demonstrated that a total of 76,435 SNPs were detected and identified as the heat-tolerance-related SNPs, which were specifically present in the highly heat-resistant rice cultivars and located in the genic regions or within 2 kbp upstream and downstream of the genes. Meanwhile, 3214 upregulated and 2212 downregulated genes with heat stress tolerance-related SNPs were detected in one or multiple RNA-seq datasets of rice under heat stress, among which 24 were located in the non-reference contigs of the rice pan-genome. We then mapped the DEGs with heat stress tolerance-related SNPs to the heat stress-resistant QTL regions. A total of 1677 DEGs, including 990 upregulated and 687 downregulated genes, were mapped to the 46 heat stress-resistant QTL regions, in which 2 upregulated genes with heat stress tolerance-related SNPs were identified in the non-reference sequences. This pan-genome resource is an important step towards the effective and efficient genetic improvement of heat stress resistance in rice to help meet the rapidly growing needs for improved rice productivity under different environmental stresses. These findings provide further insight into the functional validation of a number of non-reference genes and, especially, the two genes identified in the heat stress-resistant QTLs in rice.

Rapid Screening of 22 Polycyclic Aromatic Hydrocarbons Residues in Vegetable Oils by Gas Chromatography-Electrostatic Field Orbitrap High Resolution Mass Spectrometry.

A method for simultaneous determination of 22 polycyclic aromatic hydrocarbons (PAHs) residues in vegetable oils by gas chromatography-electrostatic field orbitrap high resolution mass spectrometry (Orbitrap GC-MS) was established. The samples were vortexed with acetonitrile, centrifuged at 8,000 r/min for 5 min, and frozen at -70°C for 10 min. The extracts of upper layer were poured out, dried with nitrogen at 40°C, redissolved in dichloromethane, and measured by Orbitrap GC-MS. The matrix interference in vegetable oil could be effectively removed by determining the accurate mass number of target compounds under the full scan mode. Six typical vegetable oil samples (soybean oil, sesame oil, peanut oil, olive oil, rapeseed oil, sunflower oil) were used for method validation. The calibration curve displayed good linearity in the range of 1-100 ng/mL, with correlation coefficients > 0.9950. The limits of detection (LODs) were in the range of 0.10-0.60 µg/kg, and the limits of quantification (LOQs) were in the range of 0.35-2.00 µg/kg. The average spiked recoveries of 22 PAHs in 6 matrices at 5, 50 and 100 µg/kg levels were 76.4-115.4%, and the average relative standard deviations (RSDs) were 1.8-10.8%. The results showed that 22 PAHs were detected in 6 types of 90 edible vegetable oil samples in the Chinese market by this method. Meanwhile, the abundance of light PAHs (LPAHs) was higher than that of heavy PAHs (HPAHs), and its relative contribution of LPAHs to the total PAHs was higher. All levels of BaP conformed to the Chinese requirement of upper limit, 10 µg/kg. However, 13.3 and 11.1% of the samples exceeded the maximum limits of BaP and PAH4 set by EU, 2 and 10 µg/kg, respectively. The total concentrations of 22 PAHs (defined as PAH22) varies greatly among different oil species, and the average PAH22 contents were listed in descending order as follows: peanut oil > sesame oil > olive oil > rapeseed oil > soybean oil > sunflower seed oil. The established method effectively avoided interference from large amounts of lipids and pigments. Therefore, the method is simple, sensitive and suitable for rapid screening and confirmation of PAHs in vegetable oil.

Ultrasonic Features and Molecular Subtype Predict Somatic Mutations in TP53 and PIK3CA Genes in Breast Cancer.

RATIONALE AND OBJECTIVES: To predict mutations in TP53 and PIK3CA genes in breast cancer using ultrasound (US) signatures and clinicopathology. MATERIALS AND METHODS: In this study, we developed and trained a model in 386 breast cancer patients to predict TP53 and PIK3CA mutations. The clinicopathological and US characteristics (including two-dimensional and color Doppler US) were investigated. Statistically significant variables were used to build predictive models, then a combined model was developed using the multivariate logistic regression analysis. RESULTS: Univariate and multivariate analyses revealed that calcifications on US was an independent predictor of TP53 mutation (p < 0.05), whereas diameter on US and US type were independent predictors of PIK3CA mutation in breast cancer (all p < 0.05). Meanwhile, Luminal B/Human epidermal growth factor receptor two-positive (HER2+), HER2+/estrogen receptor-negative (ER-), and triple-negative breast cancer (TNBC) subtypes were strong predictors of TP53 mutation (odds ratio [OR] = 3.13, 3.18, 3.44, respectively, all p < 0.05). HER2+/ER- and TNBC subtypes were negative predictors of PIK3CA mutation (OR = 0.223, 0.241, respectively, all p < 0.05). The areas under curves (AUCs) for PIK3CA mutation in the training set increased from 0.553-0.610 to 0.741 in the multivariate model that combined US features and molecular subtype, with a sensitivity and specificity of 80.6% and 58.7%, respectively. The application of the multivariate model in the validation set achieved acceptable discrimination (AUC = 0.715). For TP53 mutation, the AUC was 0.653. CONCLUSION: US is a non-invasive modality to recognize the presence of TP53 and PIK3CA mutation. The models combined with US features and molecular subtype have implications for the practical application of predicting gene mutation for individual decision-making regarding treatment planning.

Comprehensive Risk System Based on Shear Wave Elastography and BI-RADS Categories in Assessing Axillary Lymph Node Metastasis of Invasive Breast Cancer-A Multicenter Study.

Purpose: To develop a risk stratification system that can predict axillary lymph node (LN) metastasis in invasive breast cancer based on the combination of shear wave elastography (SWE) and conventional ultrasound. Materials and Methods: A total of 619 participants pathologically diagnosed with invasive breast cancer underwent breast ultrasound examinations were recruited from a multicenter of 17 hospitals in China from August 2016 to August 2017. Conventional ultrasound and SWE features were compared between positive and negative LN metastasis groups. The regression equation, the weighting, and the counting methods were used to predict axillary LN metastasis. The sensitivity, specificity, and the areas under the receiver operating characteristic curve (AUC) were calculated. Results: A significant difference was found in the Breast Imaging Reporting and Data System (BI-RADS) category, the "stiff rim" sign, minimum elastic modulus of the internal tumor and peritumor region of 3 mm between positive and negative LN groups (p < 0.05 for all). There was no significant difference in the diagnostic performance of the regression equation, the weighting, and the counting methods (p > 0.05 for all). Using the counting method, a 0-4 grade risk stratification system based on the four characteristics was established, which yielded an AUC of 0.656 (95% CI, 0.617-0.693, p < 0.001), a sensitivity of 54.60% (95% CI, 46.9%-62.1%), and a specificity of 68.99% (95% CI, 64.5%-73.3%) in predicting axillary LN metastasis. Conclusion: A 0-4 grade risk stratification system was developed based on SWE characteristics and BI-RADS categories, and this system has the potential to predict axillary LN metastases in invasive breast cancer.

Adjuvant radiotherapy shows benefit in selected stage I uterine sarcoma: A risk scoring system based on a population analysis.

BACKGROUND: The potential therapeutic benefit of adjuvant radiotherapy for patients with stage I uterine sarcoma has not been clear. In this study, we aimed to develop a risk scoring model to select the subgroup of patients with stage I uterine sarcoma who might benefit from adjuvant radiotherapy. METHODS: Patients with stage I uterine sarcoma from the Surveillance, Epidemiology, and End Results program from 2010 to 2014 were retrospectively included in this analysis. Cox proportional hazards models were performed to identify risk factors. RESULTS: A total of 947 stage I uterine sarcoma patients were included. The 5-year disease-specific survival (DSS) of the overall cohort was 75.81%. Multivariate analysis identified stage (p = 0.013), tumor grade (p <0.001) and histology (p = 0.043) as independent prognostic factors for DSS, and these factors were used to generate the risk scoring model. The low-risk group presented a better DSS than the high-risk group (95.51% vs. 49.88%, p < 0.001). The addition of radiotherapy to surgery significantly increased the DSS in the high-risk group compared with surgery alone (78.06% vs. 46.88%, p = 0.022), but no significant survival benefit was observed in the low-risk group (98.36% vs. 100%, p = 0.766). CONCLUSIONS: Our risk scoring model based on stage, tumor grade, and histology predicted the outcome of patients with stage I uterine sarcoma cancer. This system may help to select stage I uterine sarcoma cancer patients who might benefit from adjuvant radiotherapy.

Extracorporeal Shockwave Therapy as an Adjunctive Therapy for Frozen Shoulder: A Systematic Review and Meta-analysis.

BACKGROUND: The best nonsurgical treatment for frozen shoulder is still unclear. Extracorporeal shockwave therapy (ESWT) is an innovative adjunctive treatment for frozen shoulder, but its effect is still unclear. PURPOSE: To evaluate the published literature regarding the potential of ESWT as an adjunctive therapy for frozen shoulder. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: Searches were conducted in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and VIP Information databases for relevant studies between inception and November 2020. Included were randomized controlled trials (RCTs) for frozen shoulder that compared ESWT with routine treatments to controls. There were no restrictions on the treatment period, type of ESWT, or severity of symptoms. At least 1 of the following outcome indices was assessed: visual analog scale (VAS) for pain, Constant-Murley score (CMS) for shoulder function assessment, or external rotation range of movement (ER ROM). RevMan 5.3 software was used to evaluate the bias and quality of the included studies. For continuous variables, the mean difference (MD) or standardized MD (SMD) with the 95% CI was extracted. For dichotomous data, event ratios and sample sizes were extracted. RESULTS: Overall, 20 studies were included. The ESWT used as an adjunct to other interventions had better outcomes compared with control groups regarding immediate and short-term analgesic effects (immediate: MD, -1.10 [95% CI, -1.27 to -0.92], P < .00001; short-term: MD, -0.72 [95% CI, -0.94 to -0.50], P < .00001) as well as immediate function (SMD, 1.54 [95% CI, 1.19 to 1.89], P < .00001], I 2 = 0%). There was significant heterogeneity between studies for long-term analgesia (MD, -0.90 [95% CI, -1.40 to -0.41], P < .00001, I 2 = 89%) and ER ROM (MD, 10.31 [95% CI, 3.46 to 17.17], P < .003, I 2 = 93%). CONCLUSION: ESWT seems to be beneficial to patients with frozen shoulder by alleviating pain and improving function. ESWT could be used as an adjunct therapy to routine treatments, although the quality of the included RCTs was hampered by significant heterogeneity regarding long-term analgesia and joint ROM.

Aspirin damages the cell wall of Saccharomyces cerevisiae by inhibiting the expression and activity of dolichol-phosphate mannose synthase 1.

Aspirin is a commonly used anti-inflammatory, analgesic and antithrombotic drug. It has attracted attention due to its potential antifungal therapeutic effect; however, the molecular mechanism is poorly understood. Here, the effects of aspirin on the cell wall of Saccharomyces cerevisiae were explored. We observed by scanning electron microscopy that aspirin could damage the cell wall ultrastructure. Meanwhile, a cellular surface hydrophobicity (CSH) assay showed that aspirin increased the hydrophobicity of the yeast cell surface. A drug sensitivity assay indicated that the overexpression of dolichol phosphate mannose synthase 1 (DPM1) reversed the cell wall damage and decreased the CSH induced by aspirin. Importantly, aspirin decreased the expression and enzyme activity of DPM1 in S. cerevisiae. Molecular docking results demonstrated that aspirin could directly bind to the Ser141 site of DPM1. Similarly, we found that aspirin damaged the cell wall and inhibited the expression of DPM1 in Candida albicans. These findings improve the current understanding of the action mode of aspirin and provide new strategies for antifungal drug design.