Changes in the intestinal microbiota of multiple myeloma patients living in high­altitude and cold regions analyzed using 16s rRNA high­throughput sequencing.

Multiple myeloma (MM) is a plasma cell clonal disease and these plasma cells can survive in the gut. The intestinal microbiota is a complex ecosystem and its dysfunction can release persistent stimulus signals that trigger genetic mutations and clonal evolution in the gut. The present study analyzed the intestinal microbiota in fecal samples of MM patients in high-altitude and cold regions of China using 16s rRNA sequencing and analyzed significantly enriched species at the phylum and genus levels. Although no significant difference in the alpha diversity was observed between the MM and control groups, a significant difference was noted in the beta diversity. A total of 15 significant differential bacteria at the genus level were found between the two groups, among which Bacteroides, Streptococcus, Lactobacillus and Alistipes were significantly enriched in the MM group. The present study also constructed a disease diagnosis model using Random Forest analysis and verified its accuracy using receiver operating characteristic analysis. In addition, using correlation analysis, it demonstrated that the composition of the intestinal microbiota in patients with MM was associated with complement levels. Notably, the present study predicted that the signaling and metabolic pathways of the intestinal microbiota affected MM progression through Kyoto Encyclopedia of Genes and Genomes functional analysis. The present study provides a new approach for the prevention and treatment of MM, in which the intestinal microbiota may become a novel therapeutic target for MM.

Role of non­coding RNAs in UV­induced radiation effects (Review).

Ultraviolet (UV) is divided into UVA (long-wave, 320-400 nm), UVB (middle-wave, 280-320 nm) and UVC (short-wave, 100-280 nm) based on wavelength. UV radiation (UVR) from sunlight (UVA + UVB) is a major cause of skin photodamage including skin inflammation, aging and pigmentation. Accidental exposure to UVC burns the skin and induces skin cancer. In addition to the skin, UV radiation can also impair visual function. Non-coding RNAs (ncRNAs) are a class of functional RNAs that do not have coding activity but can control cellular processes at the post-transcriptional level, including microRNA (miRNA), long non-coding RNA (lncRNA) and circulatory RNA (circRNA). Through a review of the literature, it was determined that UVR can affect the expression of various ncRNAs, and that this regulation may be wavelength specific. Functionally, ncRNAs participate in the regulation of photodamage through various pathways and play pathogenic or protective regulatory roles. In addition, ncRNAs that are upregulated or downregulated by UVR can serve as biomarkers for UV-induced diseases, aiding in diagnosis and prognosis assessment. Therapeutic strategies targeting ncRNAs, including the use of natural drugs and their extracts, have shown protective effects against UV-induced photodamage. In the present review, an extensive summarization of previous studies was performed and the role and mechanism of ncRNAs in UV-induced radiation effects was reviewed to aid in the diagnosis and treatment of UV-related diseases.

Deciphering Cholesterol's Role in PD-L2 Stability: A Distinct Regulatory Mechanism From PD-L1.

Programmed cell death 1 ligand 2 (PD-L2), a member of the B7 immune checkpoint protein family, emerges as a crucial player in immune modulation. Despite its functional overlap with programmed cell death 1 ligand 1 (PD-L1) in binding to the programmed cell death protein 1 (PD-1) on T cells, PD-L2 exhibits a divergent expression pattern and a higher affinity for PD-1. However, the regulatory mechanisms of PD-L2 remain under-explored. Here, our investigations illustrate the pivotal role of cholesterol in modulating PD-L2 stability. Using advanced nuclear magnetic resonance (NMR) and biochemical analyses, we demonstrate a direct and specific binding between cholesterol and PD-L2, mediated by an F-xxx-V-xx-LR motif in its transmembrane domain, distinct from that in PD-L1. This interaction stabilizes PD-L2 and prevents its downstream degradation. Disruption of this binding motif compromises PD-L2's cellular stability, underscoring its potential significance in cancer biology. These findings not only deepen our understanding of PD-L2 regulation in the context of tumors, but also open avenues for potential therapeutic interventions.

Predicting and overcoming resistance to CDK9 inhibitors for cancer therapy.

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.

An online diagnosis method for cancer lesions based on intelligent imaging analysis.

With the popularization and application of artificial intelligence and medical image big data in the field of medical image, the universality of modes and the rapid development of deep learning have endowed multi-mode fusion technology with great development potential. Technologies of 5G and artificial intelligence have rapidly promoted the innovation of online hospitals. To assist doctors in the remote diagnosis of cancer lesions, this article proposes a cancer localization and recognition model based on magnetic resonance images. We combine a convolution neural network with Transformer to achieve local features and global context information, which can suppress the interference of noise and background regions in magnetic resonance imaging. We design a module combining convolutional neural networks and Transformer architecture, which interactively fuses the extracted features to increase the cancer localization accuracy of magnetic resonance imaging (MRI) images. We extract tumor regions and perform feature fusion to further improve the interactive ability of features and achieve cancer recognition. Our model can achieve an accuracy of 88.65%, which means our model can locate cancer regions in MRI images and effectively identify them. Furthermore, our model can be embedded into the online hospital system by 5G technology to provide technical support for the construction of network hospitals.

Burden of non-communicable diseases among adolescents and young adults aged 10-24 years in the South-East Asia and Western Pacific regions, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Although non-communicable diseases (NCDs) remain the leading causes of mortality and disability worldwide, little comprehensive or recent evidence of the burden of NCDs among adolescents and young adults in the South-East Asia and Western Pacific regions is available. We aimed to report population shifts in people aged 10-24 years and their NCD burden from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: We retrieved data from GBD 2019 for people aged 10-24 years in the South-East Asia and Western Pacific regions from 1990 to 2019. We presented population shifts and analysed deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NCDs. We also quantified the associations of deaths and DALYs with the Socio-demographic Index (SDI) and Universal Health Coverage (UHC) effective coverage index using Spearman correlation and linear regression analyses. Percentages are reported to 1 decimal place and rates are reported to 2 decimal places. FINDINGS: In 2019, there were 559·2 million young people aged 10-24 years in the South-East Asia region and 335·0 million in the Western Pacific region; India and China remained the countries with greatest number of this age group. In 1990-2019, India had an absolute increase of 139·4 million adolescents, while China had a decrease of 134·3 million. In 2019, NCDs accounted for 27·3% (95% uncertainty interval 25·1 to 29·2) and 34·6% (33·5 to 36·1) of total deaths, and 49·8% (45·3 to 54·4) and 65·1% (60·6 to 69·3) of total DALYs in the South-East Asia and the Western Pacific regions, respectively. Neoplasms, cardiovascular diseases, and mental disorders were the leading causes of NCD burden in 42 countries. Kiribati had the highest rates of deaths (62·82 [50·77 to 76·11] per 100 000 population), YLLs (4364·73 [3545·04 to 5275·63] per 100 000 population), and DALYs (9368·73 [7713·65 to 11340·99] per 100 000 population) for NCDs, whereas Australia (6976·51 [5044·46 to 9190·01] per 100 000 population) and New Zealand (6716·81 [4827·25 to 8827·69] per 100 000 population) had the largest rates of YLDs due to NCDs. From 1990 to 2019 across both regions, the rate of death due to NCDs declined by over a third (-32·8% [-41·1 to -22·9] in the South-East Asia region and -40·0% [-48·6 to -30·4] in the Western Pacific region), and DALYs decreased by about 12% (-12·0% [-16·8 to -7·7] in the South-East Asia region and -12·8% [-17·7 to -8·7] in the Western Pacific region), whereas the proportion of NCD burden relative to all-cause burden increased (45·7% [32·9 to 61·7] for deaths and 41·2% [35·2 to 48·8] for DALYs in the South-East Asia region; 11·8% [7·1 to 21·5] for deaths and 18·2% [14·6 to 22·0] for DALYs in the Western Pacific region). The rate of deaths and DALYs due to NCDs decreased monotonically alongside increases in SDI (rs=-0·57 [95% CI -0·81 to -0·32] for deaths and rs=-0·30 [-0·61 to 0·03] for DALYs). The rate of deaths (rs=-0·89 [95% CI -0·97 to -0·80]) and DALYs (rs=-0·67 [-0·93 to -0·41]) due to NCDs also decreased alongside increases in the UHC effective coverage index. INTERPRETATION: Specific preventive and health service measures are needed for adolescents and young adults in countries with different levels of socioeconomic development to reduce the burden from NCDs. FUNDING: National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Structure-based discovery of IHMT-IDH1-053 as a potent irreversible IDH1 mutant selective inhibitor.

Through a structure-based irreversible drug design approach, we have discovered a highly potent IDH1-mutant inhibitor compound 16 (IHMT-IDH1-053) (IC50 = 4.7 nM), which displays high selectivity against IDH1 mutants over IDH1 wt and IDH2 wt/mutants. The crystal structure demonstrates that 16 binds to the IDH1 R132H protein in the allosteric pocket adjacent to the NAPDH binding pocket through a covalent bond with residue Cys269. 16 inhibits 2-hydroxyglutarate (2-HG) production in IDH1 R132H mutant transfected 293T cells (IC50 = 28 nM). In addition, it inhibits the proliferation of HT1080 cell line and primary AML cells which both bear IDH1 R132 mutants. In vivo, 16 inhibits 2-HG level in a HT1080 xenograft mouse model. Our study suggested that 16 would be a new pharmacological tool to study IDH1 mutant-related pathology and the covalent binding mode provided a novel approach for designing irreversible IDH1 inhibitors.

GRB10 is a novel factor associated with gastric cancer proliferation and prognosis.

GRB10 and its family members GRB7 and GRB14 were important adaptor proteins. They regulated many cellular functions by interacting with various tyrosine kinase receptors and other phosphorus-containing amino acid proteins. More and more studies have shown that the abnormal expression of GRB10 is closely related to the occurrence and development of cancer. In our current research, expression data for 33 cancers from the TCGA database was downloaded for analysis. It was found that GRB10 was up-regulated in cholangiocarcinoma, colon adenocarcinoma, head and neck squamous carcinoma, renal chromophobe, clear renal carcinoma, hepatocellular carcinoma, lung adenocarcinoma, lung squamous carcinoma, gastric adenocarcinoma and thyroid carcinoma. Especially in gastric cancer, the high GRB10 expression was closely associated with poorer overall survival. Further research showed that the knockdown of GRB10 inhibited proliferation and migration ability in gastric cancer. Also, there was a potential binding site for miR-379-5p on the 3'UTR of GRB10. Overexpression of miR-379-5p in gastric cancer cells reduced GRB10-regulated gastric cancer proliferation and migration capacity. In addition, we found that tumor growth was slower in a mice xenograft model with knock down of GRB10 expression. These findings suggested that miR-379-5p suppresses gastric cancer development by downregulating GRB10 expression. Therefore, miR-379-5p and GRB10 were expected to be potential targets for the treatment of gastric cancer.

Cuproptosis-associated genes and immune microenvironment characterization in breast cancer.

Excess Cu can cause cell death as a cofactor for essential enzymes. The relationship between cuproptosis-associated genes (CAGs) and breast cancer (BR) is not completely investigated. Here, the transcriptome expression and mutation profile data of BR samples from the Cancer Genome Atlas database were retrieved to identify CAGs. Patients with BR were clustered using consensus clustering. A least absolute shrinkage and selection operator analysis was then performed to construct a CAGs risk signature. As a result, all 13 cuproptosis regulators were significantly differentially expressed between BR and normal samples; among them, 9 cuproptosis genes were correlated with prognoses. Patients with BR were separated into 2 clusters that were associated with patient survival, clinical phenotypes, and immune infiltration, Based on the components of cuproptosis. Subsequently, genes differentially expressed between clusters were obtained, and 11 CAGs were ultimately incorporated into the risk signature. Functional analyses revealed that the risk signature correlated with patient outcomes, ER, PR, HER2 expression, and BR IHC subtypes. Additionally, immune microenvironment analyses showed that CAGs-high-risk patients exhibited lower immune cell infiltration and immune functions. Furthermore, high-risk BR patients had higher TMB, lower immune checkpoint expression, higher m6A gene expression, and higher tumor stemness. Finally, the immunophenoscore analysis revealed that the risk signature could potentially predict the immune response in BR and help guide the application of various immunotherapeutic drugs. Overall, the newly constructed CAGs risk signature presented a predictive value for the prognosis and tumor microenvironment of BR patients and can be further used in the guidance of immunotherapy for BR.

Dual effect of ultraviolet B on cholesterol efflux and regulated by ultraviolet radiation resistance-associated gene-mediated autophagy.

OBJECTIVE: In addition to diet and metabolism, the occurrence of foam cells and atherosclerosis are also related to environmental factors. Individual studies have shown that ultraviolet B (UVB) can regulate the progression of atherosclerosis, but with different results. Whether or not UVB has a dual effect on atherosclerosis and what mechanism is involved has not been reported. METHODS: After THP-1-derived foam cells were treated with UVB in different ways, the effects of UVB on foam cells were investigated by western blotting, cholesterol efflux experiment, oil red O staining and other methods. RESULTS: UVB plays a dual role on foam cell formation, and this effect is related to cholesterol efflux. UVB of 50 mJ/cm2 can promote cholesterol efflux in foam cells, while UVB of 200 mJ/cm2 can inhibit cholesterol efflux. UVB induces cholesterol efflux from foam cells in an autophagy-dependent manner, as the beneficial effect of UVB at 50 mJ/cm2 can be reversed by the autophagy inhibitor 3-Methyladenine (3-MA). In addition, silencing the expression of ultraviolet radiation resistance-associated gene (UVRAG) can inhibit autophagy and reduce cholesterol efflux, and overexpressing UVRAG yields the opposite result. CONCLUSION: In conclusion, our research proves that UVB exhibits a dual role in foam cell formation by regulating cholesterol efflux. Further more, we also reveal that UVRAG-mediated autophagy is the underlying mechanism of UVB-induced cholesterol efflux.

A SARS-CoV-2 vaccine based on conjugation of SARS-CoV-2 RBD with IC28 peptide and mannan.

SARS-CoV-2 is a particularly transmissible virus that causes a severe respiratory disease known as COVID-19. Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. The receptor-binding domain (RBD) of SARS-CoV-2 spike protein elicits most neutralizing antibodies during viral infection and is an ideal antigen for vaccine development. In particular, RBD expressed by E. coli is amenable to low cost and high-yield manufacturability. The adjuvant is necessitated to improve the immunogenicity of RBD. IC28, a TLR5-dependent adjuvant, is a peptide from bacterial flagellin. Mannan is a ligand of TLR-4 or TLR-2 and a polysaccharide adjuvant. Here, IC28 and mannan were both covalently conjugated with RBD from E. coli. The conjugate (RBD-IC28-M) elicited high RBD-specific IgG titers, and a neutralization antibody titer of 201.4. It induced high levels of Th1-type cytokines (IFN-γ) and Th2-type cytokines (IL-5 and IL-10), along with high antigenicity and no apparent toxicity to the organs. The mouse sera of the RBD-IC28-M group competitively interfered with the interaction of RBD and ACE2. Thus, conjugation with IC28 and mannan additively enhanced the humoral and cellular immunity. Our study was expected to provide the feasibility to develop an affordable, easily scalable, effective vaccine SARS-CoV-2 vaccine.

Regulation of PD-L1 through direct binding of cholesterol to CRAC motifs.

Cholesterol, an essential molecule for cell structure, function, and viability, plays crucial roles in the development, progression, and survival of cancer cells. Earlier studies have shown that cholesterol-lowering drugs can inhibit the high expression of programmed-death ligand 1 (PD-L1) that contributes to immunoevasion in cancer cells. However, the regulatory mechanism of cell surface PD-L1 abundance by cholesterol is still controversial. Here, using nuclear magnetic resonance and biochemical techniques, we demonstrated that cholesterol can directly bind to the transmembrane domain of PD-L1 through two cholesterol-recognition amino acid consensus (CRAC) motifs, forming a sandwich-like architecture and stabilizing PD-L1 to prevent downstream degradation. Mutations at key binding residues prohibit PD-L1-cholesterol interactions, decreasing the cellular abundance of PD-L1. Our results reveal a unique regulatory mechanism that controls the stability of PD-L1 in cancer cells, providing an alternative method to overcome PD-L1-mediated immunoevasion in cancers.

[Temporal and Spatial Variations in Black Carbon Aerosol in Different Atmospheric Background Stations in China from 2006 to 2020].

Black carbon (BC) aerosol emissions are complex and have important environmental and meteorological effects. In China, the temporal and spatial variations in BC in different atmospheric environmental conditions need to be fully understood. Based on the long-term observational BC data in seven atmospheric background stations in China from 2006 to 2020, combined with meteorological data, emission source data, enhanced vegetation index (EVI) data, and aerosol optical depth (AOD) data, we comprehensively analyzed the characteristics of temporal and spatial variations, long-term evolution, and influencing factors of BC in China. The results showed that the BC and AOD values of different atmospheric environments in China were quite different, and BC positively contributed to AOD. The spatial distribution was high in the east and low in the west owing to the differences in emission sources and meteorological conditions. The ρ(BC) and AOD values were higher to the east of the "Hu Huanyong" line, such as at the Mt. Longfeng, Shangdianzi, Lin'an, and Jinsha stations, where the average values were (1699±2213)-(3392±2131) ng·m-3 and 0.36±0.32-0.72±0.37, respectively. These values were lower to the west of the "Hu Huanyong" line, such as at the Akedala, Mt. Waliguan, and Shangri-La stations, where the average values were (287±226)-(398±308) ng·m-3 and 0.20±0.13-0.22±0.19, respectively. The interannual variability in BC included differences between different atmospheric background stations, which could be divided into four categories:low interannual variability, such as at the Akedala station; an initial increase followed by a decrease and subsequent stabilization, such as at the Mt. Waliguan station; an initial decrease followed by stabilization, such as at the Shangri-La station; and an initial stabilization followed by a decrease, such as at the Mt. Longfeng, Shangdianzi, Jinsha, and Lin'an stations. Seasonal variations in BC included differences in different atmospheric background stations. The BC mass concentrations were lowest in autumn and higher in winter and spring west of the "Hu Huanyong" line and were highest in winter and lowest in summer east of the "Hu Huanyong" line. BC contributed to the AOD being larger in all stations in the spring and summer and contributed less at the stations west of the "Hu Huanyong" line in autumn and the stations east of the "Hu Huanyong" line in winter. The diurnal variations in BC were mainly bimodally distributed in the different atmospheric background stations, but the peak times varied in different stations and seasons.

Comprehensive quantitative malignant risk prediction of pure grouped amorphous calcifications: clinico-mammographic nomogram.

Background: Pure grouped amorphous calcifications are classified as Breast Imaging Reporting and Data System (BI-RADS) category 4B suspicious calcifications and recommended for biopsy. However, the biopsies often reveal benign findings, especially in screening mammograms (92.4-97.2%). Methods: Mammograms of 699 pure grouped amorphous calcifications with final pathological results were analyzed in this retrospective study. The maximum span (MS) of the group of calcifications and the MS of the parallel/vertical direction of the mammary duct (MPS/MVS) were measured, and the MPS to MVS ratio was calculated. Based on the MS and ratio, 2 prediction nomograms with other clinic-mammographic features were developed. The discrimination performance of the models was assessed and compared by the area under the receiver operating characteristic curve (AUC). Scatterplots were created to determine the cutoff values with fewer misdiagnoses of malignant calcifications and fewer false positives. Results: Ultimately, 2 prediction models were successfully developed based on the 4 risk factors of age, purpose of the mammogram, whether multiple or single calcifications, and the MS [odds ratio (OR) =1.06, P=0.02]/ratio (OR =6.05, P<0.001). Both models had good discrimination. The ratio model performed better than the MS model in the training cohort (AUC of 0.875 and 0.834, respectively, P=0.003) and validation cohort (AUC 0.908 and 0.867, respectively, P=0.047). For the group with probably benign calcifications (as detected by the ratio nomogram), the malignancy rates were 2.7% [95% confidence interval (CI): 1.00% to 6.53%] and 1.19% (95% CI: 0.06% to 7.37%) in the training and validation cohorts, respectively, and 44.12% and 47.70% of benign biopsies were detected in the training and validation cohorts, respectively. Conclusions: The clinico-mammographic quantitative malignancy risk prediction nomogram showed favorable discrimination and calibration performance. The ratio model showed better diagnostic efficiency than the MS model, and identified >40% of benign biopsies.

Predicting the pathological grade of breast phyllodes tumors: a nomogram based on clinical and magnetic resonance imaging features.

OBJECTIVE: To explore the potential factors related to the pathological grade of breast phyllodes tumors (PTs) and to establish a nomogram to improve their differentiation ability. METHODS: Patients with PTs diagnosed by post-operative pathology who underwent pretreatment magnetic resonance imaging (MRI) from January 2015 to June 2020 were retrospectively reviewed. Traditional clinical features and MRI features evaluated according to the fifth BI-RADS were analyzed by statistical methods and introduced to a stepwise multivariate logistic regression analysis to develop a prediction model. Then, a nomogram was developed to graphically predict the probability of non-benign (borderline/malignant) PTs. RESULTS: Finally, 61 benign, 73 borderline and 48 malignant PTs were identified in 182 patients. Family history of tumor, diameter, lobulation, cystic component, signal on fat saturated T2 weighted imaging (FS T2WI), BI-RADS category and time-signal intensity curve (TIC) patterns were found to be significantly different between benign and non-benign PTs. The nomogram was finally developed based on five risk factors: family history of tumor, lobulation, cystic component, signal on FS T2WI and internal enhancement. The AUC of the nomogram was 0.795 (95% CI: 0.639, 0.835). CONCLUSION: Family history of tumor, lobulation, cystic components, signals on FS T2WI and internal enhancement are independent predictors of non-benign PTs. The prediction nomogram developed based on these features can be used as a supplemental tool to pre-operatively differentiate PTs grades. ADVANCES IN KNOWLEDGE: More sample size and characteristics were used to explore the factors related to the pathological grade of PTs and establish a predictive nomogram for the first time.

Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study.

Zika virus (ZIKV) leads to congenital microcephaly and anomalies and severe neurological diseases such as Guillain-Barre syndrome. Safe and effective vaccines are necessitated to deal with these severe health threats. As an ideal antigen, the domain III of the envelope protein (EDIII) of ZIKV can evoke potent neutralizing antibodies without any antibody-dependent enhancement (ADE) effect. However, EDIII necessitates to be formulated with an antigen delivery system or adjuvants to improve its immunogenicity. Hemoglobin (Hb) regulates inflammation, cytokine levels, and activate macrophage. Mannan is a polysaccharide of the fungal cell wall with an immunomodulatory activity. In this study, EDIII was conjugated with Hb and mannan, using the disulfide bond as the linker. Hb and mannan both functioned as the adjuvants. Conjugation of Hb and mannan acted as the delivery system for EDIII. The structure of EDIII was essentially maintained upon conjugation of Hb and mannan. The intracellular release of EDIII from the conjugate (HM-EDIII-2) was achieved by reduction of the glutathione-sensitive disulfide bond. As compared with EDIII, HM-EDIII-2 elicited high EDIII-specific IgG titers and high levels of Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10), along with no apparent toxicity to the organs. Moreover, the pharmacokinetic study revealed a prolonged serum exposure of HM-EDIII-2 to the immune cells. Thus, HM-EDIII-2 could boost a strong humoral and cellular immune response to EDIII. Our study was expected to provide the feasibility necessary to develop a robust and potentially safe ZIKV vaccine.

Development and Validation of a Diagnostic Nomogram for the Preoperative Differentiation Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenomas.

OBJECTIVE: The aim of the study was to construct and validate a nomogram for differentiating follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). METHODS: Two hundred patients with pathologically confirmed thyroid follicular neoplasms were retrospectively analyzed. The patients were randomly divided into a training set (n = 140) and validation set (n = 60). Baseline data including demographics, CT (computed tomography) signs, and radiomic features were analyzed. Predictive models were developed and compared to build a nomogram. The predictive effectiveness of it was evaluated by the area under receiver operating characteristic curve (AUC). RESULTS: The CT model, radiomic model and combination model showed excellent discrimination (AUCs [95% confidence interval] = 0.847 [0.766-0.928], 0.863 [0.746-0.932], 0.913 [0.850-0.975]). The nomogram based on the combination model showed remarkable discrimination in the training and validation sets. The calibration curves suggested good consistency between actual observation and prediction. CONCLUSIONS: This study proposed a nomogram that can accurately and intuitively predict the malignancy potential of follicular thyroid neoplasms.

Malignancy Risk Stratification Prediction of Amorphous Calcifications Based on Clinical and Mammographic Features.

PURPOSE: To explore the potential factors influencing the malignancy risk of amorphous calcifications and establish a predictive nomogram for malignancy risk stratification. PATIENTS AND METHODS: Consecutive mammograms from January 2013 to December 2018 were retrospectively reviewed. Traditional clinical features were recorded, and mammographic features were estimated according to the 5th BI-RADS. Included calcifications were randomly divided into the training and validation cohorts. A nomogram was developed to graphically predict the risk of malignancy (risk) based on stepwise multivariate logistic regression analysis. The discrimination and calibration performance of the model were assessed in both the training and validation cohorts. RESULTS: Finally, 1018 amorphous calcifications with final pathological results in 907 women were identified with a malignancy rate of 28.4% (95% CI: 25.7%, 31.3%). The malignancy rates of subgroups divided by the distribution of calcifications, quantity of calcifications, age, menopausal status and family history of cancer were significantly different. There were 712 cases and 306 cases in the training and validation cohorts. The prediction nomogram was finally developed based on four risk factors, including age and distribution, maximum diameter and quantity of calcifications. The AUC of the nomogram was 0.799 (95% CI: 0.761, 0.836) in the training cohort and 0.795 (95% CI: 0.738, 0.852) in the validation cohort. CONCLUSION: On mammography, the distribution, maximum diameter and quantity of calcifications are independent predictors of malignant amorphous calcifications and can be easily obtained in the clinic. The nomogram developed in this study for individualized malignancy risk stratification of amorphous calcifications shows good discrimination performance.

Optimizing the Catheter Care and Maintenance Strategy of Short-Term Catheterization among Hospitalized Patients in Microbiological Approach.

OBJECTIVE: To optimize the allocation of nursing resources, we investigate an alternative strategy for indwelling catheter cleaning. METHODS: The present study involved a total of 117 male patients and 54 female patients, who were catheterized after urinary surgery from Aug 2018 to Feb 2019. The samples of indwelling catheter cleaning solutions were divided by two parts for microbiological culture and microbiome analysis. RESULTS: No pathogenic bacteria were observed in the microbiological culture of the indwelling catheter cleaning samples from 24 h-uncleaned group and 48 h-uncleaned group. The microbiome analysis also showed no significant difference in bacterial diversity and quantity of the indwelling catheter cleaning solutions between the two groups. CONCLUSION: The indwelling catheter cleaning for male after urinary surgery can be prolonged to 48 h. The result of this study provided reliable basis for optimizing the allocation of clinical nursing resources.

[Isoflurane preconditioning inhibits caspase-11-related noncanonical pyroptosis pathway to alleviate hepatic ischemia-reperfusion injury in mice].

OBJECTIVE: To study the protective effect of isoflurane preconditioning on hepatic ischemia-reperfusion (I/R) injury mediated by the noncanonical pyroptosis pathway. METHODS: Thirty C57BL/6 mice were randomly divided into sham-operated group, isoflurane group and I/R group, and in the latter two groups, hepatic I/R injury was induced by clamping the portal vein for 30 min. In isoflurane group, the mice were pretreated with 1.4% isoflurane 30 min before the surgery. The protective effect of isoflurane preconditioning against hepatic I/R injury was evaluated by assessing the pathological score of HE staining of the liver tissue and serum ALT and AST levels. Serum IL-1ß and IL-18 levels and the protein expression of GSDMS were detected by ELISA and Western blotting to evaluate the inhibitory effect of isoflurane preconditioning on pyroptosis. Western blotting and immunofluroescence were used to detect the protein expression of caspase-11 in the liver tissues to evaluate the inhibitory effect of isoflurane preconditioning on noncanonical pyroptosis pathway. RESULTS: The Suzuki's score of the liver tissue was significantly higher in I/R group than in the sham group (P < 0.05), while the score in the isoflurane group was significantly lower than that in the I/R group (P < 0.05). Serum ALT and AST levels significantly increased in the sham group (P < 0.05), and were significantly lower in isoflurane group than in I/R group (P < 0.05). The serum levels of IL-1ß and IL-18 were significantly higher in I/R group than in sham group (P < 0.05), and were significantly lower in isoflurane group than in I/R group (P < 0.05). The expression of GSDMD in the I/R group was significantly higher than that in sham group, and was significantly lower in isoflurane group than in I/R group (P < 0.05). The hepatic expression of caspase-11 was significantly higher in I/R group than in sham group (P < 0.05), and was significantly lower in isoflurane group than in I/R group (P < 0.05). CONCLUSIONS: Isoflurane preconditioning has protective effect against hepatic I/R injury, which is related to the inhibition of the noncanonical pyroptosis pathway.