Investigation of RBM10 mutation and its associations with clinical and molecular characteristics in EGFR-mutant and EGFR-wildtype lung adenocarcinoma.

Background: RBM10 is commonly mutated in lung adenocarcinoma (LUAD). However, its role in the pathogenesis of LUAD remains undefined. EGFR-mutant LUAD represents a distinct subset of non-small cell lung cancer (NSCLC). The function of RBM10 in tumor pathogenesis is supposed to differ between EGFR-mutant and EGFR-wt LUAD. This study aimed to interrogate the prevalence of RBM10 mutation in a large cohort of Chinese patients with LUAD and investigate the association of RBM10 mutation with clinical and molecular characteristics of EGFR-mutant and EGFR-wt LUAD. Methods: Tumor sequencing data from 2848 Chinese patients with LUAD were retrospectively reviewed and analyzed. The prevalence of RBM10 was also compared with other three cohorts: OrigMed (n = 1222), MSKCC (n = 1267), and TCGA (n = 566). The associations of RBM10 mutation with clinical and molecular characteristics were assessed. An external cohort of 182 patients with LUAD who received PD-1 inhibitor were used to investigate the association of RBM10 mutation with clinical outcomes upon immunotherapy. Results: Our cohort showed a higher prevalence of RBM10 in EGFR-mutant LUAD than in EGFR-wt LUAD (14.8 % vs. 6.5 %, p < 0.001). The enrichment of RBM10 mutations in EGFR-mutant LUAD was also seen in another Chinese cohort (OrigMed: 14.9 % vs. 7.8 %, p < 0.001), but not in the two western cohorts (MSKCC: 7.4 % vs. 9.5 %, p = 0.272; TCGA: 8.1 % vs. 6.7 %, p = 0.624). RBM10 mutations co-occurred more frequently with EGFR L858R mutations (23.7 %) than with other types of EGFR mutations (19 del: 7.7 %; other: 7.1 % in others, p < 0.001). In EGFR-mutant LUAD, RBM10 mutations were more commonly found in stage I (18.2 %) and II (21.8 %) vs. stage III (9.4 %) and IV (11.3 %) tumors (p < 0.001). The proportion of PD-L1 positive expression in EGFR-mutant LUAD with concomitant RBM10 mutation was not different from that those without RBM10 mutations (41.8 % vs. 47.9 %, p = 0.566). In contrast, RBM10 mutation occurred more frequently in EGFR-wt LUAD at stage II-IV (stage II: 12.0 %, stage III: 8.7 %, stage IV: 6.6 %) than at stage I (2.8 %). EGFR-wt LUAD with concomitant RBM10 mutations had higher proportions of PD-L1 expression positivity (78.9 % vs. 61.9 %, p = 0.014) and higher tumor mutational load (8.97 vs. 2.99 muts/Mb, p < 0.001) than those without. Patients with EGFR-wt LUAD who also harbored RBM10 loss of function (LOF) mutations had a longer median PFS upon immunotherapy than those with RBM10 non-LOF mutations (7.15 m vs. 2.60 m, HR = 4.83 [1.30-17.94], p = 0.010). Conclusion: We comprehensively investigated RBM10 mutations in a Chinese cohort with LUAD. Compared to western cohorts, a significant enrichment of RBM10 mutations in EGFR-mutant LUAD compared to EGFR-wildtype LUAD in the Chinese population. RBM10 mutation shows different associations with clinical and molecular characteristics between EGFR-mutant and EGFR-wt LUAD, suggesting a divergent mechanism between these two subsets via which RBM10 deficiency contribute to tumor pathogenesis. The findings contribute to our understanding of the molecular landscape of LUAD and highlight the importance of considering population-specific factors in cancer genomics research.

High hyperdiploid karyotype with ≥ 49 chromosomes represents a heterogeneous subgroup of acute myeloid leukemia with differential TP53 mutation status and prognosis: a single-center study from China.

High hyperdiploid karyotype with ≥ 49 chromosomes (which will be referred to as HHK) is rare in acute myeloid leukemia (AML). The European leukemia network (ELN) excluded those harboring only numerical changes (with ≥ 3 chromosome gains) from CK and listed them in the intermediate risk group, while the UK National Cancer Research Institute Adult Leukaemia Working Group classification defined ≥ 4 unrelated chromosome abnormalities as the cutoff for a poorer prognosis. Controversies occurred among studies on the clinical outcome of HHK AML, and their molecular characteristics remained unstudied. We identified 1.31% (133/10,131) HHK cases within our center, among which 48 cases only had numerical changes (NUM), 42 had ELN defined adverse abnormalities (ADV) and 43 had other structural abnormalities (STR). Our study demonstrated that: (1) No statistical significance for overall survival (OS) was observed among three cytogenetic subgroups (NUM, STR and ADV) and HHK AML should be assigned to the adverse cytogenetic risk group. (2) The OS was significantly worse in HHK AML with ≥ 51 chromosomes compared with those with 49-50 chromosomes. (3) The clinical characteristics were similar between NUM and STR group compared to ADV group. The former two groups had higher white blood cell counts and blasts, lower platelet counts, and mutations associated with signaling, while the ADV group exhibited older age, higher chromosome counts, higher percentage of myelodysplastic syndrome (MDS) history, and a dominant TP53 mutation.

ß-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.

Recent studies have demonstrated that ß-catenin in dendritic cells (DCs) serves as a key mediator in promoting both CD4 and CD8 T cell tolerance, although the mechanisms underlying how ß-catenin exerts its functions remain incompletely understood. Here, we report that activation of ß-catenin leads to the up-regulation of inhibitory molecule T-cell immunoglobulin and mucin domain 3 (Tim-3) in type 1 conventional DCs (cDC1s). Using a cDC1-targeted vaccine model with anti-DEC-205 engineered to express the melanoma antigen human gp100 (anti-DEC-205-hgp100), we demonstrated that CD11c-ß-cateninactive mice exhibited impaired cross-priming and memory responses of gp100-specific CD8 T (Pmel-1) cells upon immunization with anti-DEC-205-hgp100. Single-cell RNA sequencing (scRNA-seq) analysis revealed that ß-catenin in DCs negatively regulated transcription programs for effector function and proliferation of primed Pmel-1 cells, correlating with suppressed CD8 T cell immunity in CD11c-ß-cateninactive mice. Further experiments showed that treating CD11c-ß-cateninactive mice with an anti-Tim-3 antibody upon anti-DEC-205-hgp100 vaccination led to restored cross-priming and memory responses of gp100-specific CD8 T cells, suggesting that anti-Tim-3 treatment likely synergizes with DC vaccines to improve their efficacy. Indeed, treating B16F10-bearing mice with DC vaccines using anti-DEC-205-hgp100 in combination with anti-Tim-3 treatment resulted in significantly reduced tumor growth compared with treatment with the DC vaccine alone. Taken together, we identified the ß-catenin/Tim-3 axis as a potentially novel mechanism to inhibit anti-tumor CD8 T cell immunity and that combination immunotherapy of a DC-targeted vaccine with anti-Tim-3 treatment leads to improved anti-tumor efficacy.

Amide and Multihydroxyl Complementary Tailored Metal-Organic Framework with Enhanced Glycan Affinity for Efficient Glycoproteomic Analysis.

Protein glycosylation is ubiquitous and crucial for regulating biological processes in organisms. Given the heterogeneity and low abundance of glycoproteins, efficient and specific enrichment procedures are required for the mass spectrometry analysis of glycopeptides. Hydrophilic interaction liquid chromatography (HILIC) has emerged as an effective strategy for glycopeptide enrichment. However, the relatively weak hydrophilic affinity restricts the achievement of a satisfactory enrichment performance. Here, we presented a rational design of an amide and multihydroxyl complementary tailored metal-organic framework, denoted as U6N/Pv@Glc, which exhibited ultrahydrophilicity and enhanced glycan affinity. Our results demonstrated a significant increase in glycopeptide coverage after enrichment, accompanied by extremely low detection limits (0.05 fmol µL-1) and high selectivity (IgG/BSA, 1:4000) as evaluated using trypsin-digested standard glycoproteins. A total of 379 glycopeptides and 247 intact glycopeptides (containing a total of 1577 site-specific N-glycans) were identified and characterized within human serum samples from individuals with type 2 diabetes in-depth. Additionally, we extended the application of this material to capture undigested glycoproteins, demonstrating potential compatibility with top-down MS analysis. These results highlight the promising potential of this novel material for comprehensive glycoproteomic analysis of every potential aspect.

Molecular phylogeny reveals cryptic diversity in Sibynophis from China (Serpentes: Sibynophiidae).

The elucidation of species diversity and distribution is critical within the fields of evolution, genetics, and conservation. The genus Sibynophis contains rare snakes that have historically received little attention. In this study, we conducted comprehensive sampling and use both mitochondrial and nuclear genetic markers to explore Sibynophis species diversity within China. Our findings revealed that S. c. miyiensis should be considered synonymous with S. c. grahami, and S. c. grahami should be gave a specific rank as S. grahami. In addition, we discovered S. triangularis was new to China and Myanmar. Based on the specimens and molecular phylogeny results, we redefined the species distribution boundaries of each Chinese species.

High-throughput detection of mycophenolic acid in human plasma based on sensitive and rapid fluorescence nitrogen-doped carbon dots sensing platform.

In this experiment, a water-soluble, nitrogen-doped yellow-green fluorescent N-doped carbon dots (N-CDs) were synthesized by one-step hydrothermal method using ß-cyclodextrin as carbon source and L-phenylalanine as nitrogen source. The fluorescence quantum yield of the obtained N-CDs was as high as 9.96%, and the N-CDs exhibited photostability at different pH, ionic strength and temperature. The morphology of the N-CDs was approximately spherical with an average particle size of about 9.4 nm. Based on the fluorescence enhancement effect of mycophenolic acid (MPA) on N-CDs, a quantitative detection method of MPA was established. This method had good selectivity and high sensitivity for MPA. The fluorescence sensing system was applied to the detection of MPA in human plasma. The linear range of MPA were 0.06-3 µg·mL-1 and 3-27 µg·mL-1 with a detection limit of 0.016 µg·mL-1, and the recoveries were 97.03∼100.64 % with the RSDs of 0.13∼2.90 %. The interference experiment results showed that the interference of other coexisting substances, including Fe3+, can be ignored in the actual detection. Comparing the results measured by the established method with the EMIT method, it was found that the results obtained by the two methods were similar, and the relative error was within ± 5 %. This study provided a simple, rapid, sensitive, selective and effective method for the quantitative analysis of MPA, and was expected to be applied to clinical MPA blood concentration monitoring.

Endoscopic manifestations and treatment outcomes of asymptomatic gastric metastases from primary lung adenocarcinoma: Report of two cases.

Metastatic spread of lung adenocarcinoma to the stomach is rare and most gastric metastases are discovered at the advanced stage due to certain symptoms. The present study reported two cases of asymptomatic gastric metastases from lung adenocarcinoma presenting as diminutive nodules or erosion endoscopically. The manifestations were also visualized under magnifying endoscopy with blue laser imaging (BLI-ME), the two cases share certain common characteristics under BLI-ME, such as an obviously widened intervening part and extended subepithelial capillary network, which indicated that lesions developed beneath the superficial epithelium. Target biopsy and further immunohistochemical staining confirmed that the gastric lesions were metastatic from primary lung cancer. None of the two patients were candidates for surgery due to multiple distant metastases, but the gastric metastases regressed to scars after systemic anticancer therapy. These two cases were presented in order to improve the current understanding of the endoscopic manifestations of early gastric metastases from lung cancer, and the outcomes may demonstrate that systemic treatment is effective for eliminating early gastric metastatic lesions.

Rapid and sensitive fluorescence determination of oxytocin using nitrogen-doped carbon dots as fluorophores.

In this work, a novel nitrogen (N)-doped carbon dots (N-CDs) was prepared with quercetin as the carbon source and o-phenylenediamine as the nitrogen source by hydrothermal synthesis, and their application as fluorophores for selective and sensitive determination of oxytocin were reported. The fluorescence quantum yield of the as-prepared N-CDs, which exhibited good water solubility and photostability, was about 6.45 % using rhodamine 6 G as reference substance, and the maximum excitation (Ex) and emission (Em) wavelength were 460 nm and 542 nm, respectively. The results illustrated that the direct fluorescence quenching of N-CDs fluorophore for the detection of oxytocin achieved good linearity in the range of 0.2-5.0 IU/mL and 5.0-10.0 IU/mL, the correlation coefficients were 0.9954 and 0.9909, respectively, and the detection limit was 0.0196 IU/mL (S/N = 3). The recovery rates were 98.8∼103.8 % with RSD= 0.93 %. The interference experiments showed that common metal ions, possible impurities introduced in production and coexisting excipients in the preparation had little adverse influence on selective detection of oxytocin by the developed N-CDs based fluorescent detection method. The mechanism study on the fluorescence quenching of N-CDs by oxytocin concentrations under the given experimental conditions demonstrated that there were internal filtration effect and static quenching in the system. The developed fluorescence analysis platform for the detection of oxytocin had been proved to be rapid, sensitive, specific and accurate, and to be used for the quality inspection of oxytocin.

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes.

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

Targeted therapy for the treatment of gliomas with multifunctional orange emissive carbon dots.

As a nano-material, carbon dots have been extensively studied and applied in many ways. Herein, iron-doped orange emissive carbon dots (ICDs) were easily synthesized using the hydrothermal method and coupled with Trf and glucose oxidase (GOD) simply by virtue of the abundant functional groups on their surface. The resulting carbon dots were named IGTCDs. The obtained IGTCDs possessed targeting, therapeutic and imaging functions, achieving the enzymolysis of glucose, the decomposition of H2O2 and the release of reactive oxygen species (ROS) sequentially in gliomas as a multifunctional nano-catalyst, and achieving an efficient glioma targeted killing effect. On the basis of the ideal biocompatibility of the IGTCDs with a cell survival rate of over 85%, even at a high concentration (500 µg ml-1), the IGTCDs, which were coupled substances present within the organism, glucose oxidase and transferrins, showed an obvious inhibitory effect on the growth of tumor cells, and the survival rate of the C6 cells was only 28.10% at 300 µg ml-1. The highly efficient anti-tumor effect was further demonstrated in the treatment of mice suffering from glioma, and the tumor inhibition rate was increased to 56.21-98.32%. This safe and effective multifunctional tumor inhibitor could be conveniently synthesized in large quantities, verifying the feasibility of the anti-tumor therapy based on the tumor microenvironment (TME), creating a novel method for the application of carbon dots in tumor treatment and providing a novel, reasonable and effective method for the treatment of cancer and gliomas.

[Study on Application of RVD Regimen Sequential Auto-HSCT in the Treatment of Multiple Myeloma Evaluated by Propensity Score Matching].

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION: Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.

Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities.

As the most potent professional antigen presenting cells, dendritic cells (DCs) have the ability to activate both naive CD4 and CD8 T cells. Recognized for their exceptional ability to cross-present exogenous antigens to prime naive antigen-specific CD8 T cells, DCs play a critical role in generating CD8 T cell immunity, as well as mediating CD8 T cell tolerance to tumor antigens. Despite the ability to potentiate host CD8 T cell-mediated anti-tumor immunity, current DC-based cancer vaccines have not yet achieved the promised success clinically with the exception of FDA-approved Provenge. Interestingly, recent studies have shown that type 1 conventional DCs (cDC1s) play a critical role in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies including immune checkpoint blockade (ICB). Together with promising clinical results in neoantigen-based cancer vaccines, there is a great need for DC-based vaccines to be further developed and refined either as monotherapies or in combination with other immunotherapies. In this review, we will present a brief review of DC development and function, discuss recent progress, and provide a perspective on future directions to realize the promising potential of DC-based cancer vaccines.

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma.

5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non-cancerous tissues was assessed using reverse transcription-quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI-H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced-stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI-H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.

Effect of wound irrigation on the prevention of surgical site infections: A meta-analysis.

We performed a meta-analysis to evaluate the effect of wound irrigation on the prevention of surgical site infections. A systematic literature search up to January 2022 was done and 24 studies included 4967 subjects under surgery at the start of the study; antibiotic irrigation was used with 1372 of them, 1261 were aqueous povidone-iodine irrigation, and 2334 were saline irrigation or no irrigation for surgical site infections prevention in all surgical populations. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the effect of different wound irrigation on the prevention of surgical site infections by the dichotomous method with a random or fixed-influence model. Antibiotic irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.48; 95% CI, 0.36-0.62, P < .001) compared with saline irrigation or no irrigation for the subject under surgery. Aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.40; 95% CI, 0.20-0.81, P = .01) compared with saline irrigation or no irrigation for the subject under surgery. Antibiotic irrigation and aqueous povidone-iodine irrigation significantly lowered surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery. Further studies are required.

Plasmacytoid Dendritic Cells and Cancer Immunotherapy.

Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy.

Inflammatory markers in postoperative cognitive dysfunction for patients undergoing total hip arthroplasty: a meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a poorly understood disorder, very common even after total hip arthroplasty (THA). It is widely considered that inflammation response play a role in the pathogenesis of POCD. AIMS: The aim of the present study was to investigate whether inflammation cytokine concentrations could serve as biomarkers for POCD in patients undergoing THA. METHODS: A systematic search of databases was conducted to retrieve publications measuring circulating inflammatory markers of patients with and without POCD after THA. Inflammatory markers identified in more than two studies were pooled. The standardized mean difference (SMD) and the 95% confidence interval (95% CI) were calculated for each outcome. Fail-safe N statistics was calculated to estimate possible publication bias. RESULTS: The pooled incidence rate of POCD after THA by combining 11 cohort studies was 31%. A total of five inflammatory markers, CRP, S-100B, IL-1ß, IL-6 and TNF-α, were assessed. Significantly higher pre-operative CRP (P = 0.012) and S-100B (P < 0.0001) as well as post-operative CPR (P = 0.005) and IL-6 (P < 0.0001) at 6 h were found in POCD compared with non-POCD patients undergoing THA. Fail-safe N statistics revealed that these results are robust. DISCUSSION: The current evidence suggests that some of the inflammatory markers, including CRP, S-100B, and IL-6, were correlated with the occurrence of POCD after THA. CONCLUSION: Monitor of inflammatory markers might help early diagnosis of POCD after THA and development of preventive strategies.

Potential effects of the nursing work environment on the work-family conflict in operating room nurses.

BACKGROUND: The nursing working environment is an important subsystem in the hospital environment. A good working environment could have a positive impact on nurses. However, the work-family conflict and unsatisfactory working environment could significantly reduce their working enthusiasm, efficacy as well as the overall quality of the nursing, increase their fatigue, and thereby compromise their career status. AIM: To explore the possible status quo and to analyze the correlation between work environment perception and the work-family conflict among nurses in the operating room. METHODS: A total of 312 operating room nurses from two first-class hospitals at Grade 2 and two first-class hospitals at Grade 3 in China from May to September 2017 were included in this research using the cluster sampling method. The data, including the general information questionnaire, the practice environment scale of the nursing work index (PES-NWI), and the work-family conflict scale, were systematically collected. Pearson correlation analysis was applied to analyze the correlation between the two scores, with influencing factors analyzed by hierarchical regression analysis. RESULTS: A total of 312 questionnaires were issued, and the response rate and effective questionnaire rate were both 96.15% (300/312). The total scores of the PES-NWI scale and the work-family conflict scale were 3.07 ± 0.43 (vs maximum up to 4 points) and 52.32 ± 8.79 (vs maximum up to 90 points), respectively. The scores of the PES-NWI scale were negatively correlated with that of work-family conflict scale (all P < 0.05). The perception of the nursing work environment and the number of night shifts per month were the major factors contributing to the work-family conflict (all P < 0.05). CONCLUSION: The nursing work environment and the work-family conflict among nurses in the operating room were both found at a medium level with a negative correlation between the two.

DC-Derived Exosomes for Cancer Immunotherapy.

As the initiators of adaptive immune responses, DCs play a central role in regulating the balance between CD8 T cell immunity versus tolerance to tumor antigens. Exploiting their function to potentiate host anti-tumor immunity, DC-based vaccines have been one of most promising and widely used cancer immunotherapies. However, DC-based cancer vaccines have not achieved the promised success in clinical trials, with one of the major obstacles being tumor-mediated immunosuppression. A recent discovery on the critical role of type 1 conventional DCs (cDC1s) play in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies, however, has highlighted the need to further develop and refine DC-based vaccines either as monotherapies or in combination with other therapies. DC-derived exosomes (DCexos) have been heralded as a promising alternative to DC-based vaccines, as DCexos are more resistance to tumor-mediated suppression and DCexo vaccines have exhibited better anti-tumor efficacy in pre-clinical animal models. However, DCexo vaccines have only achieved limited clinical efficacy and failed to induce tumor-specific T cell responses in clinical trials. The lack of clinical efficacy might be partly due to the fact that all current clinical trials used peptide-loaded DCexos from monocyte-derived DCs. In this review, we will focus on the perspective of expanding current DCexo research to move DCexo cancer vaccines forward clinically to realize their potential in cancer immunotherapy.

Edge-Enhanced with Feedback Attention Network for Image Super-Resolution.

Significant progress has been made in single image super-resolution (SISR) based on deep convolutional neural networks (CNNs). The attention mechanism can capture important features well, and the feedback mechanism can realize the fine-tuning of the output to the input. However, they have not been reasonably applied in the existing deep learning-based SISR methods. Additionally, the results of the existing methods still have serious artifacts and edge blurring. To address these issues, we proposed an Edge-enhanced with Feedback Attention Network for image super-resolution (EFANSR), which comprises three parts. The first part is an SR reconstruction network, which adaptively learns the features of different inputs by integrating channel attention and spatial attention blocks to achieve full utilization of the features. We also introduced feedback mechanism to feed high-level information back to the input and fine-tune the input in the dense spatial and channel attention block. The second part is the edge enhancement network, which obtains a sharp edge through adaptive edge enhancement processing on the output of the first SR network. The final part merges the outputs of the first two parts to obtain the final edge-enhanced SR image. Experimental results show that our method achieves performance comparable to the state-of-the-art methods with lower complexity.

DC-Based Vaccines for Cancer Immunotherapy.

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.