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To evaluate the addition of digital breast tomosynthesis (DBT) in the diagnosis of breast lesions in symptomatic young Chinese women (≤30 years) diagnosed with Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 on ultrasound, and demonstrate the potential use of combining DBT with ultrasound.This retrospective analysis included 5 years of digital mammography (DM) and DBT data (January 2015 to July 2020). In total, 768 DBT and DM examinations were performed in 713 young women. The results were determined by pathological assessment. Diagnostic performance was measured based on the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic area under the curve (AUC).Compared with DM alone, DBT + DM increased the sensitivity from 82.5% to 93.2%, specificity from 70.8% to 84%, accuracy from 74% to 86.5%, NPV from 93.6% to 97.4% (all p0.01). The AUC of DBT + DM (0.946, 95% confidence interval [CI]: 0.927-0.960) was greater than that of DM (0.884, 95% CI: 0.859-0.905; p0.001). The differences in the BI-RADS category distributions of malignant and benign lesions were both statistically significant (p0.001). DM alone led to 36 false-negative diagnoses, whereas the inclusion of DBT identified breast cancer in 22 of those cases. There were 4.9% (10/206) false-negative diagnoses in ultrasound. After adding DBT, four breast cancers were detected. An additional six breast cancers were diagnosed by biopsy based on an assessment of BI-RADS 4A by DBT/DM.DBT + DM significantly improves the diagnostic performance in this young population, especially in young people with higher breast density. Moreover, DBT is an effective supplementary examination to ultrasound.

While the best technique for pancreatic anastomosis during Whipple’s procedure remains controversial, laparoscopic pancreaticoduodenectomy (LPD) has been rapidly increasing in popularity. Because of their feasibility and reliability, new pancreatic anastomosis techniques may have vital roles when adapted for LPD. Here, we describe a new pancreaticojejunostomy (PJ) technique using three sutures (termed the “three sutures” PJ technique), which facilitates pancreatic anastomosis during total LPD. A total of 149 patients who underwent LPD using the “three sutures” PJ technique at three hospitals were included in this study (81 patients at Guangdong Provincial People’s Hospital [GDPH], 60 patients at Sun Yat-Sen Memorial Hospital [SMH], and 8 patients at Affiliated Hospital of Guangdong Medical University [AHGMU]). Data on the demographic characteristics, operative outcomes, and postoperative results (pancreatic fistula rate, mortality rate, and length of hospital stay) of these patients were collected and analyzed. A surgical video showing the details of the “three sutures” PJ method was included. The mean operation times at GDPH, SMH, and AHGMU were 4.08 ± 0.99 h, 4.65 ± 1.53 h, and 4.67 ± 0.64 h, respectively, and the average PJ times were 17.96 ± 3.49 min, 18.19 ± 2.63 min, and 22.5 ± 3.96 min, respectively. The numbers of grade B pancreatic fistulas were 9 (11.11%), 2 (3.33%), and 1 (12.50%), respectively, and two patients had grade C fistulas, one each at GDPH and SMH. The numbers of clinically relevant postoperative pancreatic fistula (CR-POPF) were 10 (12.35%), 3 (5.00%), and 1 (12.50%) in each center, respectively. The overall rate of CR-POPF was 9.40% (14/149) among patients of all three centers. The perioperative mortality rate was 0%. The “three sutures” PJ technique for total LPD is a safe and reliable method, with a low risk of pancreatic fistula, short anastomosis time, and steep learning curve.

In this study, the hydroforming process parameters of a bi-layered X-type tube are designed and optimized by exploring the response surface methodology. First, UG software is used for model setup of the bi-layered X-type tube and mold, which is imported into DYNAFORM software for further numerical simulation and calculation of the hydroforming process. The main parameters of the loading path are selected as experimental factors for the methodology. The maximum thinning ratio of the inner and outer tubes, the maximum clearance between bi-layers, and the limit fillet radius of the top branch tube are used as test evaluation indicators. In accordance with effective evaluation indexes, perturbation plots, optimization evaluation criteria, and contour graphs, the relationship among the main influencing factors is analyzed and the process parameters of the optimal loading path are screened. Finally, a comparison between experimental results and simulation is made and shows that the error is within 6%, which indicates that the optimization method of the hydroforming process parameter in a bi-layered X-type tube has high feasibility.

This paper aimed to explore pelvic lymphadenectomy for gynecological malignant tumors guided by computed tomography angiography (CTA) images under region-growing algorithm (RGA). 100 cases of malignant tumor patients who received pelvic lymphadenectomy in hospital from January 2018 to January 2020 were analyzed. Patients were classified into control group (CTA image) and experimental group (RGA-based CTA image), each with 50 cases. The overall accuracy (OA) of the pelvic CT image segmentation parameters under RGA, the watershed segmentation algorithm (WA), and the swarm intelligence optimization algorithm (SIOA) was compared. Comparisons of segmentation parameters, denoising performance, and CT imaging of patients as well as diagnosis rate and total efficiency rate were carried out. The results showed that overall accuracy (OA) of RGA was considerably higher versus watershed segmentation algorithm (WA) and swarm intelligence optimization algorithm (SIOA). However, false positive rate (FPR) and false negative rate (FNR) of RGA were greatly lower than those of other algorithms. RGA greatly improved the accuracy of pelvic tumor detection. The peak signal-to-noise ratio (PSNR) of RGA was superior to that of WA and SIOA, but differences in edge preservation index (EPI) value were not significant. The diagnosis rate of the experimental group was 48/50 (96%), while the diagnosis rate by manual means was 38/50 (76%). For the diagnosis rate and total efficiency, results of the experimental group were evidently higher in contrast to the control group ( P < 0.05 ). In conclusion, under RGA, CTA image-guided pelvic lymphadenectomy had good segmentation accuracy and denoising performance, and it was superior in total efficiency and diagnosis rate, which was worthy of clinical promotion.

Current clinical agents for autoimmunity disorders treatment often cause substantial adverse effects and safety concerns, owing to non-specific immune modulation. Due to the prominent contribution of effector T cells in pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), and preferential location of co-stimulatory receptor-ligand pair OX40-OX40L at the inflamed sites, selectively targeting autoaggressive T cells by blockade OX40-OX40L, might represent an alternative strategy. Herein, we developed a new strategy to antagonize OX40-OX40L interaction by engineering a cell membrane derived nanovesicles (NVs) expressing OX40 receptors (OX40 NVs), and explored their potential for autoimmune disorders therapy. OX40 NVs showed specific binding capability to inflamed HUVECs in vitro, it also possessed distinct arthritic-targeting capacity in RA inflamed joints, and preferential accumulation in IBD inflamed colon. OX40 NVs efficiently suppressed the progression of both RA and IBD diseases through reducing CD4+OX40+ T cells population, and proinflammatory cytokines (i.e., TNF-α and IL-1β), while reinforcing Tregs immune-suppressive effect, with superior therapeutic efficacy than anti-OX40L. Additionally, dexamethasone (DEX) loading can further enhance the potential of OX40 NVs for RA treatment. Owing to their preferential localization to inflamed sites, and potent immune-suppression ability, targeting OX40-OX40L blockade by OX40 NVs for autoimmune therapy is highly promising.

BACKGROUND Evaluating tumor-infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored. PURPOSE To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level. STUDY TYPE Retrospective. POPULATION A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown previously that insulin receptor substrate 2 (IRS2), a molecule highly critical to insulin resistance and metabolism, has an anti-inflammatory role in Th2-skewed lung inflammation and pulmonary vascular remodeling. Here, we investigated the hypothesis that IRS2 has an immunomodulatory role in human and experimental PH. Expression analysis showed that IRS2 was significantly decreased in the pulmonary vasculature of patients with pulmonary arterial hypertension and in rat models of PH. In mice, genetic ablation of IRS2 enhanced the hypoxia-induced signaling pathway of Akt and Forkhead box O1 (FOXO1) in the lung tissue and increased pulmonary vascular muscularization, proliferation, and perivascular macrophage recruitment. Furthermore, mice with homozygous IRS2 gene deletion showed a significant gene dosage-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy in response to hypoxia. Functional studies with bone marrow-derived macrophages isolated from homozygous IRS2 gene-deleted mice showed that hypoxia exposure led to enhancement of the Akt and ERK signaling pathway followed by increases in the pro-PH macrophage activation markers, vascular endothelial growth factor-A and arginase 1. Our data suggest that IRS2 contributes to anti-inflammatory effects by regulating macrophage activation and recruitment, which may limit the vascular inflammation, remodeling, and right ventricular hypertrophy that are seen in PH pathology. Restoring the IRS2 pathway may be an effective therapeutic approach for the treatment of PH and right heart failure.

This work aimed to study the application of pelvic floor dynamic images of magnetic resonance imaging (MRI) based on the particle swarm optimization (PSO) algorithm in female stress urinary incontinence (SUI). 20 SUI female patients were selected as experimental group, and another 20 healthy females were taken as controls. PSO algorithm, K-nearest neighbor (KNN) algorithm, and back propagation neural network (BPNN) algorithm were adopted to construct the evaluation models for comparative analysis, which were then applied to 40 cases of female pelvic floor dynamic MRI images. It was found that the model proposed had relatively high prediction accuracy in both the training set (87.67%) and the test set (88.46%). In contrast to the control group, there were considerable differences in abnormal urethral displacement, urethral length changes, bladder prolapse, and uterine prolapse in experimental patients ( P < 0.05 ). After surgery, the change of urethral inclination angle was evidently reduced ( P < 0.05 ). To sum up, MRI images can be adopted to assess the occurrence of female SUI with abnormal urethral displacement, shortening of urethra length, bladder prolapse, and uterine prolapse. After surgery, the abnormal urethral movement was slightly improved, but there was no obvious impact on bladder prolapse and uterine prolapse.

Melanoma is a highly aggressive cancer which often forms metastatic tumors in the lung, leading to sharply reduced patients’ survival rate. Effectively treating these tumors thus could improve late stage melanoma with lung metastasis. In this study, we fabricated a Cys-Arg-Glu-Lys-Ala with N-methylated Glu (CR(NMe)EKA) decorated disk shaped nano vehicle to co-deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PTX) to lung melanoma tumor sites (TRAIL-[ND-PTX]CR(NMe)EKA). These nanodisks displayed better tumor-targeting and penetration capability than spherical nanoparticles, while the fibronectin-targeting CR(NMe)EKA motif also increased the tumor accumulation of loaded drugs. The combined usage of TRAIL and PTX both killed tumor cells and reduced local nutrition supply, leading to stronger overall anti-tumor effect. This TRAIL-[ND-PTX]CR(NMe)EKA system performed remarkably better than free paclitaxel and also significantly elongated survival rate of melanoma lung metastasis bearing mice, without displaying significant toxicity. Hence, this designing strategy and the fabricated nanoplatform possess potential for further development.

Breast cancer was the leading cause of newly diagnosed cases of tumors in 2020, ranking as the second highest cause of female death. Chemotherapy remains the conventional treatment of choice for breast tumors in most clinical cases. However, it is often accompanied by a poor prognosis and severe side effects, resulting from an insufficient accumulation of the drug at tumor sites and an unsystematic distribution of the drug across the body. Inspired by the fact that breast tumor cells overexpress integrin α2β1 on the surface, we designed and constructed an integrin α2β1 targeting DGEA-modified liposomal doxorubicin (DGEA-Lipo-DOX) platform for application in breast cancer therapy. The DGEA-Lipo-DOX was stable with a uniform particle size of 121.1 ± 3.8 nm and satisfactory drug encapsulation. Demonstrated in vitro and in vivo, the constructed platform exhibited improved antitumor ability. The DGEA-Lipo-DOX showed 4-fold enhanced blood circulation and 6-fold increased accumulation of DOX at the tumor sites compared to those of free DOX, resulting in a significantly enhanced antitumor efficacy in tumor-bearing mice. A preliminary safety evaluation suggested that the systemic toxicity of DOX was relieved by DGEA-Lipo delivery. Collectively, binding integrin α2β1 by DGEA may represent an alternative therapeutic strategy for potentially safer breast cancer treatment.

The occurrence and characterization of carbapenemase-producing Enterobacteriaceae from companion animals in Guangzhou, China, are investigated. Six isolates (2.3%, 6/257) were positive for blaNDM-5...

Qi-Xing Tian,1,* Zhi-Hui Zhang,1,* Qing-Lin Ye,1 Shen Xu,1 Qian Hong,1 Wei-Yang Xing,1 Lei Chen,1 De-Xin Yu,1 De-Xiang Xu,2,3 Dong-Dong Xie1 1Department of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Toxicology, Anhui Medical University, Hefei, 230032, People’s Republic of China; 3Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: De-Xiang XuDepartment of Toxicology, Anhui Medical University, Hefei, 230032, People’s Republic of ChinaTel +86 138 6674 1832Email xudex@126.comDong-Dong XieDepartment of Urology, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of ChinaTel +86 138 6670 0010Email xiedd_urology@163.comPurpose: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin.Materials and Methods: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze β-catenin ubiquitination.Results: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial–mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKTSer473 and GSK-3βSer9. Moreover, LPS induced phosphorylation of GSK-3βSer9 in the “disruption complex”, and then inhibited phosphorylation and ubiquitination of cytoplasmic β-catenin, leading to β-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3β and β-catenin pathways.Conclusion: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.Keywords: β-catenin, EMT, lipopolysaccharide, melatonin, prostate cancer

Objective. To determine the effect and mechanism of the anti-inflammatory agent ghrelin on pulmonary vascular dysfunction (PVD) in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) rat models. Methods. Thirty-two adult male Sprague Dawley rats (n = 16/group) were randomly divided into ghrelin and saline groups, wherein ghrelin (10 nmol/kg) or saline was subcutaneously administered. After 30 min, eight rats from each group were randomly selected, and LPS (5 mg/kg) or saline was administered by intratracheal instillation to induce ALI. Four hours after establishing the ALI rat model, the mean pulmonary arterial pressure (mPAP), mean right ventricular systolic pressure (RVSP), levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF), BALF cell count, wet-to-dry (W/D) lung weight ratios, and myeloperoxidase (MPO) activity in lung tissue for all four groups (ghrelin, ghrelin + ALI, saline, and saline + ALI) were measured. Immunohistochemical staining to detect alpha-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) expression was performed to assess the intrapulmonary arterial wall thickness and the proliferation of smooth muscle cells, respectively. Results. The ghrelin-pretreated ALI rats showed lower mPAP, RVSP, PCNA expression, MPO activity, W/D lung weight ratio, TNF-α and IL-6 levels, and BALF cell count than the saline-pretreated ALI rats, but ghrelin had no effect on the intrapulmonary arterial wall thickness of ALI rats. Conclusion. Our results confirmed the association between inflammation and PVD in ALI and suggested that the suppression of inflammation by ghrelin pretreatment could protect LPS-induced ALI rats against PVD.

Clinical studies have suggested that internal and/or external aversive cues may produce a negative affective-motivational component whereby maladaptive responses (plasticity) of dural afferent neurons are initiated contributing to migraine chronification. However, pathophysiological processes and neural circuitry involved in aversion (unpleasantness)-producing migraine chronification are still evolving. An interdisciplinary team conducted this narrative review aimed at reviewing neuronal plasticity for developing migraine chronicity and its relevant neurocircuits and providing the most cutting-edge information on neuronal mechanisms involved in the processing of affective aspects of pain and the role of unpleasantness evoked by internal and/or external cues in facilitating the chronification process of migraine headache. Thus, information presented in this review promotes the understanding of the pathophysiology of chronic migraine and contribution of unpleasantness (aversion) to migraine chronification. We hope that it will bring clinicians’ attention to how the maladaptive neuroplasticity of the emotion brain in the aversive environment produces a significant impact on the chronification of migraine headache, which will in turn lead to new therapeutic strategies for this type of pain.

Accumulating evidence demonstrates that the cerebellum is involved in a variety of cognitive functions. Recently, impaired auditory-motor integration for vocal control has been identified in patients with cerebellar degeneration, characterized by abnormally enhanced vocal compensations for pitch perturbations. However, the causal relationship between the cerebellum and auditory feedback during vocal production remains unclear. By applying anodal transcranial direct current stimulation (a-tDCS) over right cerebellum, the present study investigated cerebellar contributions to auditory-motor processing of feedback errors during vocal pitch regulation. Twenty young adults participated in a frequency-altered-feedback (FAF) task, in which they vocalized vowel sounds and heard their voice unexpectedly pitch-shifted by ± 50 or ± 200 cents. Active or sham cerebellar a-tDCS was applied either prior to or during the FAF task. Compensatory vocal responses to pitch perturbations were measured and compared across the conditions. Active cerebellar a-tDCS led to significantly larger and slower vocal compensations for pitch perturbations than sham stimulation. Moreover, this modulatory effect was observed regardless of the timing of cerebellar a-tDCS as well as the size and direction of the pitch perturbation. These findings provide the first causal evidence that the cerebellum is essentially involved in auditory feedback control of vocal production. Enhanced and slowed vocal compensations caused by cerebellar a-tDCS may be related to its inhibition on the prefrontal cortex that exerts inhibitory control over vocal compensation behavior, suggesting the importance of the cerebrocerebellar connections in this feedback control process.

Wnt-Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event-free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo-HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in 'cell morphogenesis involved in differentiation', 'haematopoietic cell lineage', 'platelet activation, signalling and aggregation' and 'mitochondrial RNA metabolic process' signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo-HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.

Aims: Using Single-cell RNA sequencing (scRNA-seq), we explored the spatiotemporal heterogeneity of pancreatic neuroendocrine tumors (pNETs) and the underlying mechanism for malignant progression. Methods: scRNA-seq was conducted on three tumor tissues (two primary tissues from different sites, one liver metastatic lesion), one normal liver tissue, and peripheral blood mononuclear cells from one patient with a metastatic G2 pNET, followed by bioinformatics analysis and validation in a pNETs cohort. Results: The transcriptome data of 24.544 cells were obtained. We identified subpopulations of functional heterogeneity within malignant cells, immune cells, and fibroblasts. There were intra- and inter-heterogeneities of cell subpopulations for malignant cells, macrophages, T cells, and fibroblasts among all tumor sites. Cell trajectory analysis revealed several hallmarks of carcinogenesis, including the hypoxia pathway, metabolism reprogramming, and aggressive proliferation, which were activated at different stages of tumor progression. Evolutionary analysis based on mitochondrial mutations defined two dominant clones with metastatic capacity. Finally, we developed a gene signature (PCSK1 and SMOC1) defining the metastatic potential of the tumor and its prognostic value was validated in a cohort of thirty G1/G2 patients underwent surgical resection. Conclusions: Our scRNA-seq analysis revealed intra- and intertumor heterogeneities in cell populations, transcriptional states, and intercellular communications among primary and metastatic lesions of pNETs. The single-cell level characterization of the spatiotemporal dynamics of malignant cell progression provided new insights into the search for potential novel prognostic biomarkers of pNETs.

Objective: To understand the distribution of drug susceptibility test results of opportunistic infections of tuberculosis and non-tuberculous bacilli in AIDS patients. Methods: The AIDS patients who were hospitalized in our hospital from January 2016 to June 2019 were collected as the research objects, and patients with opportunistic tuberculosis and non-tuberculous bacilli from AIDS patients were screened for drug susceptibility tests, and the distribution characteristics of drug susceptibility were analyzed. Results: 179 strains of tuberculosis and non-tuberculous mycobacteria were isolated from the specimens of AIDS patients, including 135 cases of tuberculosis mycobacteria and 44 cases of non-tuberculous mycobacteria. In the results of the drug susceptibility test, most strains of Mycobacterium tuberculosis showed sensitivity to commonly used drugs, and a few strains showed resistance; most strains of non-tuberculous mycobacteria showed resistance, and a few strains showed sensitivity. Conclusion: AIDS opportunistic infection of Mycobacterium tuberculosis and non-tuberculous mycobacteria have significant differences in drug sensitivity test results. Timely detection and analysis are of great significance to the diagnosis and treatment of the disease.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Pancreatic carcinoma elevates quickly and thus has a high mortality rate. Therefore, early treatment is essential for treating pancreatic carcinoma. KRAS is the most frequently identified and one of the earliest mutations in pancreatic tumorigenesis. Thus, the KRAS-mutant cell is an ideal target for the treatment of pancreatic carcinoma, especially at the early stage. KRAS mutation increases macropinocytosis in pancreatic cancer cells, enhancing the internalization of exosomes. Because acquiring natural exosomes could be laborious and their encapsulation efficiency is often unsatisfactory, we aimed to develop a delivery system that mimics the Kras-mutant cell targeting capability of exosomes but is easier to generate and has better loading efficiency. For this purpose, we constructed a hybrid nanoplatform by fusing CLT (Celastrol)-Loaded PEGylated lipids with the DC2.4 cell membrane (M-LIP-CLT) to achieve targeted treatment of Kras-mutant pancreatic cancer. This hybrid nanoplatform improved CLT tumor accumulation and showed excellent anti-cancer efficiency both in vitro and in vivo with increased safety. These results suggest that M-LIP-CLT is an effective drug delivery system for targeted therapy against pancreatic carcinoma, and the fusion strategy showed attractive potential for further development.

Multiple myeloma (MM) is a hematologic tumor with monoclonal proliferation of malignant plasma cells in the bone marrow. Fascin (FSCN) is an actin-binding protein that plays a crucial role in cell migration and invasion, contributing to tumor metastasis. There are three members (FSCN1-3) in FSCN family. However, the prognostic role of FSCN family in MM remains unclear. In this study, we used four independent Gene Expression Omnibus (GEO) datasets to explore the relationships between FSCN1-3 expression profiles and patient survival in MM. We found that FSCN1 was dramatically down-regulated in MM compared to normal donors (p < 0.001) and monoclonal gammopathy of undetermined significance (MGUS) (p = 0.032). Patients with high expression of FSCN1 and FSCN2 had significantly longer OS (p = 0.023 and 0.028, respectively). Univariate and multivariate analysis showed that FSCN1 (p = 0.003, 0.002) and FSCN2 (p = 0.018, 0.013) were independent favorable prognostic factors for OS in MM. Moreover, the combination of high expression of FSCN1 and FSCN2 could effectively predict both longer EFS (p = 0.046) and OS (p = 0.015). Our study suggested that FSCN1 and FSCN2 can be used as favorable biomarkers for predicting clinical outcomes in MM.

Endogenous miRNA expression patterns are extremely cell-type-specific, thereby offering high prediction accuracy for different cell identities. Here, a DNA-tetrahedron-based "AND" logic gate is utilized as a molecular device that recognizes dual-miRNA inputs through strand hybridization to activate a computation cascade that produces controlled singlet oxygen in live cells, resulting in the death of the target cell.

Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miRNAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the MECP2 gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of in vitro tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor κB (NF-κB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting MECP2 for human EUE.

Objective. Soluble CD206 (sCD206) is considered a macrophage activation marker, and a previous study proved it as a potential biomarker to predict the severity of anti-melanoma differentiation-associated gene 5- (anti-MDA-5-) positive dermatomyositis- (DM-) associated interstitial lung disease (ILD). To investigate the role of sCD206 in various subtypes of DM, we evaluated the serum level of sCD206 in patients with different myositis-specific autoantibodies besides anti-MDA-5 and clarified its clinical significance. Methods. Commercial enzyme-linked immunosorbent assay kits were used to detect serum concentrations of sCD206 in 150 patients with DM and 52 healthy controls (HCs). Correlations between sCD206 levels and clinical features, laboratory examinations, and pulmonary function test parameters were analysed. Results. The median concentrations of serum sCD206 in DM patients were significantly higher than those in HCs ( p < 0.0001 ). Furthermore, median sCD206 levels were elevated in patients with ILD ( p = 0.001 ), especially in those with rapidly progressive ILD (RP-ILD) ( p < 0.0001 ). In addition, sCD206 levels were negatively correlated with the pulmonary function test results, including the percent predicted forced vital capacity ( r = − 0.234 , p = 0.023 ), percent predicted forced expiratory volume in one second ( r = − 0.225 , p = 0.030 ), and percent predicted carbon monoxide diffusion capacity ( r = − 0.261 , p = 0.014 ). Age- and gender-adjusted multivariable analysis showed that sCD206 was an independent prognostic factor for RP-ILD in patients with DM. A longitudinal study showed that sCD206 levels were positively correlated with the physician global assessment visual analog scale scores ( β = 54.201 , p = 0.001 ). Conclusion. Serum sCD206 levels were significantly increased in patients with DM and significantly associated with RP-ILD, suggesting that sCD206 is an important biological predictor of RP-ILD in patients with DM.

The family of resistin-like molecules (RELMs) consists of four members in rodents (RELMα/FIZZ1/HIMF, RELMβ/FIZZ2, Resistin/FIZZ3, and RELMγ/FIZZ4) and two members in humans (Resistin and RELMβ), all of which exhibit inflammation-regulating, chemokine, and growth factor properties. The importance of these cytokines in many aspects of physiology and pathophysiology, especially in cardiothoracic diseases, is rapidly evolving in the literature. In this review article, we attempt to summarize the contribution of RELM signaling to the initiation and progression of lung diseases, such as pulmonary hypertension, asthma/allergic airway inflammation, chronic obstructive pulmonary disease, fibrosis, cancers, infection, and other acute lung injuries. The potential of RELMs to be used as biomarkers or risk predictors of these diseases also will be discussed. Better understanding of RELM signaling in the pathogenesis of pulmonary diseases may offer novel targets or approaches for the development of therapeutics to treat or prevent a variety of inflammation, tissue remodeling, and fibrosis-related disorders in respiratory, cardiovascular, and other systems.

Enhanced Recovery after Surgery has been proven effective for patients with gastrointestinal cancer. But radical enhanced recovery could also lead to adverse clinical outcomes. Compared with reports on the estimation of successful implementation of enhanced recovery, studies on risk factors of enhanced recovery failure are still lacking. A retrospective analysis was carried out on 102 patients in ERAS who underwent elective colon cancer surgery. This study included 102 patients with colon cancer between 2015 and 2019, defining enhanced recovery failure as postoperative length of stay over 10 days, stay in ICU over 24 h after surgery, reoperation, death, or unplanned readmission within 30 days after surgery. Univariate and multivariate analyses were performed to explore potential risk factors of failure. Aged ≥ 75, open operation, number of drainage tube over 1, re-urethral catheterization, and Clavien-Dindo grade over 2 were associated with ERAS failure, according to univariate analysis. Multivariate analysis showed that age ≥ 75 [OR 7.231; P = 0.009]; open operation (OR 3.599; P = 0.021); and number of drainage tube over 1 (OR 3.202; P = 0.020) were independent risk factors for ERAS failure. We found age ≥ 75, open operation, and number of drainage tube over 1 are independent risk factors associated with ERAS failure after colon cancer surgery.

The increasing and simultaneous pollution of plastic debris and antibiotic resistance in aquatic environments makes plastisphere a great health concern. However, the development process of antibiotic resistome in the plastisphere is largely unknown, impeding risk assessment associated with plastics. Here, we profiled the temporal dynamics of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and microbial composition in the plastisphere from initial microbial colonization to biofilm formation in urban water. A total of 82 ARGs, 12 MGEs, and 63 bacterial pathogens were detected in the plastisphere and categorized as the pioneering, intermediate, and persistent ones. The high number of five MGEs and six ARGs persistently detected in the whole microbial colonization process was regarded as a major concern because of their potential role in disseminating antibiotic resistance. In addition to genomic analysis, D2O-labeled single-cell Raman spectroscopy was employed to interrogate the ecophysiology of plastisphere in a culture-independent way and demonstrated that the plastisphere was inherently more tolerant to antibiotics than bacterioplankton. Finally, by combining persistent MGEs, intensified colonization of pathogenic bacteria, increased tolerance to antibiotic, and potential trophic transfer into a holistic risk analysis, the plastisphere was indicated to constitute a hot spot to acquire and spread antibiotic resistance and impose a long-term risk to ecosystems and human health. These findings provide important insights into the antibiotic resistome and ecological risk of the plastisphere and highlight the necessity for comprehensive surveillance of plastisphere.