Adar Regulates Drosophila melanogaster Spermatogenesis via Modulation of BMP Signaling.

The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. AIM OF THE STUDY: This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. MATERIALS AND METHODS: The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. RESULTS: CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1ß. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. CONCLUSION: This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

QUIZ: An arbitrary volumetric point matching method for medical image registration.

Rigid pre-registration involving local-global matching or other large deformation scenarios is crucial. Current popular methods rely on unsupervised learning based on grayscale similarity, but under circumstances where different poses lead to varying tissue structures, or where image quality is poor, these methods tend to exhibit instability and inaccuracies. In this study, we propose a novel method for medical image registration based on arbitrary voxel point of interest matching, called query point quizzer (QUIZ). QUIZ focuses on the correspondence between local-global matching points, specifically employing CNN for feature extraction and utilizing the Transformer architecture for global point matching queries, followed by applying average displacement for local image rigid transformation.We have validated this approach on a large deformation dataset of cervical cancer patients, with results indicating substantially smaller deviations compared to state-of-the-art methods. Remarkably, even for cross-modality subjects, it achieves results surpassing the current state-of-the-art.

Knockdown of fat mass and obesity alleviates the ferroptosis in Parkinson's disease through m6A-NRF2-dependent manner.

Emerging evidence has suggested that N6 -methyladenosine (m6 A) regulates the pathology of Parkinson's disease (PD). Nevertheless, the function of demethylase fat mass and obesity (FTO) associated pathogenesis is still not fully elucidated. Here, this research findings revealed that m6 A-modification was decreased in PD models, meanwhile, the FTO level upregulated in the PD models. Functionally, in N-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells, the ferroptosis significantly upregulated and FTO silencing mitigated the ferroptosis phenotype. Moreover, in silico assays indicated that nuclear factor erythroid 2-related factor-2 (NRF2) acted as the target of FTO, and FTO demethylated the m6 A modification from NRF2 mRNA. Furthermore, FTO impaired the NRF2 mRNA stability via m6 A-dependent pathway. Thus, our findings illustrated an important role of FTO on PD through m6 A-NRF2-ferroptosis manner. Taken together, the study revealed the potential function of FTO on PD nervous system diseases.

Construction and validation of a novel ferroptosis-related prognostic signature for lung adenocarcinoma.

Background: Lung cancer has the highest prevalence and mortality of all cancers, and lung adenocarcinoma (LUAD) occupies the largest proportion of lung cancers. Herein, this study is aimed at constructing a ferroptosis-related prognostic signature for LUAD and conducting functional analysis based on the signature, highlighting the importance of ferroptosis in LUAD. Methods: We employed RNA-sequencing (RNA-seq) and clinical data from The Cancer Genome Atlas (TCGA) database. Univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were conducted to build the ferroptosis-related genes (FRGs) prognostic signature. The efficacy of this FRG signature was further analyzed with Kaplan-Meier (KM) plot, multivariate Cox regression, and the receiver operating characteristic (ROC) curves. Enrichment analysis was used to evaluate key pathways. The expression of immunomodulators, immune infiltration status, and drug sensitivity correlation were explored to predict the response to various therapies. The expression of FRGs was validated in LUAD samples with western blot (WB) and immunohistochemistry (IHC) staining. Cell viability assay and lipid peroxidation detection were measured after small interfering RNA (siRNA) knockdown of two FRGs in lung cancer cell lines. Results: A seven-gene signature was constructed and used to divide LUAD patients into high- and low-risk groups. High-risk patients were notably related to shorter overall survival (OS), and multivariate Cox regression demonstrated that our signature was an independent predictor of OS. ROC curve analysis presented a maximum area under the curve (AUC) value of 0.740 for the experimental cohort and 0.705 for the validation cohort. The low-risk group showed higher levels of plasma cell infiltration and higher expression of programmed cell death protein 1 (PDCD1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Ferroptosis inducers such as talazoparib or cisplatin had lower IC50 values in the high-risk group, while navitoclax (BCL-2 gene family inhibition and apoptosis inducer) had higher IC50 values in the high-risk group. Additionally, peroxiredoxin-6 (PRDX6) and acyl-CoA synthetase long chain family member 3 (ACSL3) were upregulated in LUAD tissues. Lipid peroxide assay showed that silencing PRDX6 or ACSL3 promoted lipid peroxidation and ferroptosis in lung cancer cells. Conclusions: Our novel ferroptosis-related signature shows potential clinical and functional importance in LUAD patients, and further research on ferroptosis as a therapeutic target in LUAD is warranted.

Selection of hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma.

Background: Hematopoietic stem cell transplantation (HSCT) is an important treatment for T-cell lymphoblastic lymphoma/leukemia (T-LBL). To compare the efficacy and influencing factors of autologous hematopoietic stem cell transplantation (auto-HSCT) with those of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors for the treatment of T-cell lymphoblastic lymphoma/leukemia (T-LBL) and provide a basis for selection of appropriate transplant methods and donors. Methods: To provide evidence of appropriate transplant methods for these patients, we retrospectively summarized the clinical characteristics of 75 T-LBL patients receiving HSCT at Henan Cancer Hospital between March 2012 and October 2021. Overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and related factors affecting efficacy were analyzed. Results: The 3-year CIR (39.9% vs 31.1%, P=0.745), 3-year PFS (60.1% vs 49.6%, P=0.434), and 3-year OS (62.8% vs 53.0%, P=0.450) were not significantly different between the auto-HSCT and allo-HSCT groups. However, the 3-year NRM was significantly higher in the allo-HSCT group (0% vs 27.2%, P=0.033). Multivariate analysis showed that the first complete remission (CR1) after HSCT was an independent influencing factor of higher OS (HR=2.498, P=0.029) and PFS (HR=2.576, P=0.016). The absence of mediastinal invasion in patients receiving HSCT was an independent influencing factor of better PFS (HR=2.977, P=0.029) and lower CIR (HR=4.040, P=0.027). With respect to the impact of donor source, the NRM in the unrelated donor (URD) and haploid donor (HPD) groups was significantly higher than that in the auto-HSCT group (P=0.021 and P=0.003, respectively), while there was no significant difference between matched sibling donors (MSD) and auto-HSCT. Compared with the MSD-HSCT group, the auto-HSCT group showed an increasing trend in 3-year CIR (39.9 ± 11.1% vs 32.6 ± 11.2%, P=0.697) and a lower trend in 3-year OS (62.8 ± 11.4% vs 64.4 ± 12.2%, P=0.929). Conclusions: HSCT is an effective consolidation treatment option for patients with T-LBL without mediastinal invasion and with CR1 before transplantation. For CR1 patients, auto-HSCT and MSD-HSCT are effective modalities for improving survival. In non-CR1 patients without an MSD, matched unrelated donors and haploidentical donor transplantations are the best treatment options to reduce relapse and improve prognosis.

Transcription Factor VvDREB2A from Vitis vinifera Improves Cold Tolerance.

Low temperatures restrict the growth of the grapevine industry. The DREB transcription factors are involved in the abiotic stress response. Here, we isolated the VvDREB2A gene from Vitis vinifera cultivar 'Zuoyouhong' tissue culture seedlings. The full-length VvDREB2A cDNA was 1068 bp, encoding 355 amino acids, which contained an AP2 conserved domain belonging to the AP2 family. Using transient expression in leaves of tobacco, VvDREB2A was localized to the nucleus, and it potentiated transcriptional activity in yeasts. Expression analysis revealed that VvDREB2A was expressed in various grapevine tissues, with the highest expression in leaves. VvDREB2A was induced by cold and the stress-signaling molecules H2S, nitric oxide, and abscisic acid. Furthermore, VvDREB2A-overexpressing Arabidopsis was generated to analyze its function. Under cold stress, the Arabidopsis overexpressing lines exhibited better growth and higher survival rates than the wild type. The content of oxygen free radicals, hydrogen peroxide, and malondialdehyde decreased, and antioxidant enzyme activities were enhanced. The content of raffinose family oligosaccharides (RFO) also increased in the VvDREB2A-overexpressing lines. Moreover, the expression of cold stress-related genes (COR15A, COR27, COR6.6, and RD29A) was also enhanced. Taken together, as a transcription factor, VvDREB2A improves plants resistance to cold stress by scavenging reactive oxygen species, increasing the RFO amount, and inducing cold stress-related gene expression levels.

Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer.

Background: Cuproptosis is the recently defined regulatory cell death (RCD) that plays essential roles in tumorigenesis and progression. Long noncoding RNAs (lncRNAs) regulate the gene expression through various means. However, the clinical value of cuproptosis-related lncRNAs in bladder cancer (BLCA) remains poorly described. Methods: We downloaded the transcriptome sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and lasso Cox regression analyses were performed to construct the prognostic risk signature, the predictive accuracy of which was validated in the subsequent independence and stratification analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the underlying molecular mechanisms involved in the signature to explore therapeutic vulnerabilities and potential targets in BLCA. Tumor mutational burden (TMB) and tumor immune dysfunction and exclusion (TIDE) were used to estimate the response to immune checkpoint inhibitors (ICIs). We further explored the potential new drug-target candidates based on the half maximal inhibitory concentration for this patient population. Results: Fifteen cuproptosis-related lncRNAs significantly associated with survival were identified to construct the risk signature based on the normalized expression level and regression coefficient of each gene. The patients with BLCA and high-risk scores defined by the signature were associated with worse survival outcomes. The differentially expressed genes (DEGs) between the 2 risk groups had different biological activity. Furthermore, the patients in the low-risk group exhibited a higher TMB index and a lower TIDE score. The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score. Conclusions: Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population.

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis.

Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia.

Diagnosis and Treatment of a Dural Arteriovenous Fistula Involving the Superior Petrosal Vein.

OBJECTIVE: A dural arteriovenous fistula involving the superior petrosal vein (SPV DAVF) is an extremely rare condition. Therefore, its clinical presentation, imaging characteristics, treatment methods, and risk factors remain unclear. In this study, we discuss and analyze the aforementioned features of an SPV DAVF. METHODS: We retrospectively reviewed 30 patients with SPV DAVFs, with a 1-year follow-up rate of 96.67% (29 of 30). The neurological function of the patients was assessed using the modified Aminoff-Logue scale and the modified Rankin Scale score. The risk factors before and after treatment were established using univariate and multivariate logistic regression analyses. Additionally, treatments involving 3 distinct SPV DAVF drainage patterns were presented. RESULTS: Of the 30 patients, 24 were men (80.0%). Besides, the angiography images were reexamined 12 months after surgery. Univariate analyses indicated that the extent of edema (odds ratio 1.889, 95% confidence interval 1.132-3.154) and the number of draining veins (≤2) (odds ratio 10.833, 95% confidence interval 1.961-59.834) were risk factors for pretreatment modified Rankin Scale score ≥3. However, multivariate analyses revealed no statistically significant differences (P = 0.051, P = 0.055). Following the multivariate analyses, steroid pulse (odds ratio 12.153 95% confidence interval 1.080-136.772) was found to be the only significant risk factor for post-treatment difference between pretreatment and 1-year follow-up modified Rankin Scale score ≥2. CONCLUSIONS: A DAVF with SPV drainage is an uncommon type of intracranial vascular malformation. Most lesions involve the brain stem or high cervical spinal cord, thereby posing a higher risk of disability or death. Moreover, neuronal damage from persistent venous hypertension is permanent. Therefore, precise diagnosis and timely treatment are key to a good patient prognosis.

Multidrug-resistant Pseudomonas aeruginosa is predisposed to lasR mutation through up-regulated activity of efflux pumps in non-cystic fibrosis bronchiectasis patients.

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa is a frequent opportunistic pathogen that causes significant mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Although the quorum sensing (QS) system is a potential target for treatment, lasR mutants that present with a QS-deficient phenotype have been frequently reported among clinical P. aeruginosa isolates. We aimed to investigate whether antibiotic resistance would select for lasR mutants during chronic P. aeruginosa lung infection and determine the mechanism underlying the phenomenon. Methods: We prospectively evaluated episodes of chronic P. aeruginosa lung infections in NCFB patients over a 2-year period at two centers of our institution. QS phenotypic assessments and whole-genome sequencing (WGS) of P. aeruginosa isolates were performed. Evolution experiments were conducted to confirm the emergence of lasR mutants in clinical MDR P. aeruginosa cultures. Results: We analyzed episodes of P. aeruginosa infection among 97 NCFB patients and found only prior carbapenem exposure independently predictive of the isolation of MDR P. aeruginosa strains. Compared with non-MDR isolates, MDR isolates presented significantly QS-deficient phenotypes, which could not be complemented by the exogenous addition of 3OC12-HSL. The paired isolates showed that their QS-phenotype deficiency occurred after MDR was developed. Whole-genome sequencing analysis revealed that lasR nonsynonymous mutations were significantly more frequent in MDR isolates, and positive correlations of mutation frequencies were observed between genes of lasR and negative-efflux-pump regulators (nalC and mexZ). The addition of the efflux pump inhibitor PAßN could not only promote QS phenotypes of these MDR isolates but also delay the early emergence of lasR mutants in evolution experiments. Conclusions: Our data indicated that MDR P. aeruginosa was predisposed to lasR mutation through the upregulated activity of efflux pumps. These findings suggest that anti-QS therapy combined with efflux pump inhibitors might be a potential strategy for NCFB patients in the challenge of MDR P. aeruginosa infections.

Neratinib inhibits proliferation and promotes apoptosis of acute myeloid leukemia cells by activating autophagy-dependent ferroptosis.

Acute myeloid leukemia (AML) is a hematologic malignancy with increased lethality. We focused on elucidating the role of Neratinib, a tyrosine kinase inhibitor, in the progression of AML and identify the potential mechanisms. Upon the treatment of Neratinib, autophagy suppressor 3-methyladenine (3-MA) and ferroptosis stimulator Erastin, the viability and proliferation of HL-60 cells were evaluated by cell counting kit-8 and 5-Ethynyl-20-Deoxyuridine staining assays. A flow cytometer was to observe cell cycle and apoptosis. Production of reactive oxygen species (ROS) was tested via 2,7-dichlorodihydrofluorescein diacetate  assay. Additionally, malondialdehyde (MDA) content and Fe2+ activity were examined with commercial kits. LC3-II expression was examined by using immunofluoresence staining. Western blot analysis ascertained the expression of proliferation, apoptosis, ferroptosis and autophagy-associated proteins. It was noted that Neratinib notably mitigated cell viability and proliferation, cut down Ki67 and proliferating cell nuclear antigen expression. Moreover, Neratinib hindered cell cycle at G0/G1 phase whereas exacerbated apoptosis. ROS, MDA and Fe2+ activities were elevated by Neratinib, coupled with the reduced glutathione peroxidase 4, ferritin heavy chain 1 expression and enhanced acyl-CoA synthetase long-chain family member 4 expression. Furthermore, Neratinib promoted autophagy of HL-60 cells, evidenced by raised LC3-II, ATG5, Beclin1 expression and lessened p62 expression. Importantly, 3-MA eased the impacts of Neratinib on cell ferroptosis, proliferation and apoptosis, which were offset by further administration of Erastin. To conclude, Neratinib could suppress proliferation and promote apoptosis of HL-60 cells through autophagy-dependent ferroptosis.

Depression in breast cancer patients: Immunopathogenesis and immunotherapy.

Depression is a common and recurrent mental illness with a complicated etiology, but the specific pathogenesis is not clear. Breast cancer increases susceptibility to depression, which leads to a poor prognosis. Rapid advances in the understanding of tumor immunology and neuroimmunology have provided new evidence for the pathogenesis of depression. Dysfunction of immune cells and cytokines cause depression by affecting tryptophan metabolism, serotonin levels, and blood-brain barrier permeability. Dysregulation of cytokines or intestinal flora may be shared between patients with depression and breast cancer. This review presents an overview of immune dysregulation in breast cancer patients with depression and proposes future alternative research directions and interventions.

Prognostic analysis of RAS-related lncRNAs in liver hepatocellular carcinoma.

Background: Liver hepatocellular carcinoma (LIHC), whose incidence is increasing globally, is one of the most prevalent malignant cancers. RAS-related pathways are involved in the cell proliferation, migration, apoptosis, and metabolism in LIHC. Long noncoding RNAs (lncRNAs) also play important roles in the progression and prognosis of LIHC. However, the clinical role, prognostic significance, and immune regulation of RAS-related lncRNAs in LIHC remains unclear. Our study aims to construct and validate a RAS-related lncRNA prognostic risk signature that can estimate the prognosis and response to immunotherapy in LIHC. Methods: The clinical information and corresponding messenger RNA (mRNA)/lncRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and 502 RAS-related lncRNAs were identified by Pearson correlation analysis. A prognostic risk signature with 5 RAS-related lncRNAs was then developed based on the Cox regression and least absolute shrinkage and selection operator (LASSO) algorithm analyses. Subsequently, Kaplan-Meier survival curve, receiver operating characteristic (ROC) curve, and the nomogram were established to evaluate the predictive accuracy of the signature. In addition, the immune microenvironment, tumor mutation burden, and drug sensitivity associated with the signature were also analyzed in LIHC. Results: Compared with the low-risk groups, the high-risk groups had an unfavorable outcome. Multivariate regression analysis revealed that the risk score signature was the independent prognostic factor superior to the other clinical variables. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses demonstrated that the risk score was highly associated with the nuclear division, DNA replication, and immune response. The group with high risk tended to hold a lower immune escape rate and better immunotherapy efficacy, while the group with low risk was more sensitive to some small molecular targeted drugs. Conclusions: We developed a RAS-related lncRNA risk signature that was highly associated with the prognosis and response to immunotherapy and targeted drugs and which provided novel mechanistic insights into the personalized treatment and potential drug selection for patients with LIHC.

The Psychological Effect of Internet-Based Mindfulness-Based Stress Reduction on the Survivors of Breast Cancer During the COVID-19.

Objective: To examine the efficacy and the role of engagement of an internet-based Mindfulness-based Stress Reduction (iMBSR) for survivors of breast cancer (BC) during the COVID-19 period from January to March in 2020 in China. Methods: 48 survivors of BC were divided into the absentees group and the iMBSR groups according to their attending to the standardized, group-based, 8-week iMBSR. Based on practice time, survivors of BC in the iMBSR were categorized into three subgroups: group 1 (<30 min/day), group 2 (30-60 min/day), and group 3 (>60 min/day). In addition, participants were classified as partial attendees (<4 sessions) and completers (more than 4 sessions) of the iMBSR groups. All participants were evaluated for symptoms of depression, anxiety and insomnia at baseline, mid-intervention, and post-intervention. Results: After an 8-week iMBSR practice, at mid-intervention and post-intervention, participants in iMBSR group had significant improvement in scores and reduction rates of depression, anxiety, and insomnia compared to absentees. Scores of depression and insomnia, reduction rates of depression at post-intervention, scores of anxiety, reduction rates of anxiety and insomnia at mid-intervention and post-intervention, had significant differences among subgroups of practice time. Daily practice time was positively related to reduction rates of depression, anxiety and insomnia at post-intervention in the iMBSR group. Conclusion: Internet-based MBSR showed efficacy in reducing psychological symptoms among survivors of BC. For survivors of BC, iMBSR practice has a potential dose-response efficacy, with a threshold of >30 min daily practice for most optimal symptoms reduction. Trial Registration: Registration number is [ChiCTR2100044309].

Fully automated intracranial aneurysm detection and segmentation from digital subtraction angiography series using an end-to-end spatiotemporal deep neural network.

BACKGROUND: Intracranial aneurysms (IAs) are common in the population and may cause death. OBJECTIVE: To develop a new fully automated detection and segmentation deep neural network based framework to assist neurologists in evaluating and contouring intracranial aneurysms from 2D+time digital subtraction angiography (DSA) sequences during diagnosis. METHODS: The network structure is based on a general U-shaped design for medical image segmentation and detection. The network includes a fully convolutional technique to detect aneurysms in high-resolution DSA frames. In addition, a bidirectional convolutional long short-term memory module is introduced at each level of the network to capture the change in contrast medium flow across the 2D DSA frames. The resulting network incorporates both spatial and temporal information from DSA sequences and can be trained end-to-end. Furthermore, deep supervision was implemented to help the network converge. The proposed network structure was trained with 2269 DSA sequences from 347 patients with IAs. After that, the system was evaluated on a blind test set with 947 DSA sequences from 146 patients. RESULTS: Of the 354 aneurysms, 316 (89.3%) were successfully detected, corresponding to a patient level sensitivity of 97.7% at an average false positive number of 3.77 per sequence. The system runs for less than one second per sequence with an average dice coefficient score of 0.533. CONCLUSIONS: This deep neural network assists in successfully detecting and segmenting aneurysms from 2D DSA sequences, and can be used in clinical practice.

In vitro/vivo evaluation of novel mitochondrial targeting charge-reversal polysaccharide-based antitumor nanoparticle.

Mitochondrial targeting drug delivery systems have made unprecedented progress in tumor treatment. Nevertheless, the stability of systemic circulation and the effectiveness of tumor accumulation are the basis for achieving tumor subcellular targeting. This study aims to overcome the biological barrier while improving the mitochondria-targeted effect of nanoparticles based on natural polysaccharides. Novel polysaccharide-based nanoparticles, with tumor microenvironment-responsive charge-reversal and mitochondrial targeting abilities, were prepared in our study. Curcumin (Cur) was loaded into the core of a positively charged chitosan oligosaccharide (COS) derivative with mitochondrial targeting ability, and a negatively charged shell based on angelica sinensis polysaccharide (AS) derivative was wrapped in the surface of the core. At the same time, the pH-sensitive borate ester bond was formed between the shell and the core. In vitro experiments showed that mitochondrial-targeted core-shell nanoparticles achieved charge-reversal and release more Cur in the acidic tumor microenvironment. After entering into the tumor cells, the lysosomes escape was effectively realized, and more Cur was transmitted to the mitochondria. This process led to the enhancement of the cytotoxicity, the reduction of the mitochondrial membrane potential and the activation of the apoptotic pathway. The results of in vivo experiments showed that the core-shell nanoparticles efficiently delivered the drug to the tumor site and significantly prolonged the retention time of the drug in the tumor tissue. At the same time, it had excellent antitumor activity and in vivo safety for tumor-bearing nude mice.

Evaluation of Endovascular Therapy Combined with Bowel Resection Treatment on Patients with Acute Mesenteric Venous Thrombosis.

BACKGROUND: This retrospective study aims to investigate the effects of the endovascular and surgical strategy for treating patients with acute mesenteric venous thrombosis (AMVT). METHODS: We retrospectively studied 68 patients with AMVT who underwent treatment in Jinling Hospital during the period from January 2009 to December 2014. The mean age was 45 ± 12 years (range 20-72 years). All patients were treated by using the combined treatment that included endovascular treatment, damage control surgery, surgical intensive care, and intestinal rehabilitation treatment. Clinical outcomes and complications were compared during the follow-up period. RESULTS: All the 68 cases received anticoagulant treatment. However, only 24 received the endovascular intervention, 19 received surgical resection, and 25 patients received endovascular treatment combined with bowel resection. The overall mortality rate was 2.94% (2 cases). Bowel resection range significantly decreased (92 ± 14 cm vs. 162 ± 27 cm, t = -2.377, P = 0.022) in the combination therapy group, when compared with the surgery group. During the 1-year follow-up period, 4 cases suffered from short bowel syndrome. CONCLUSIONS: Our study indicates that AMVT can be successfully treated with the early improvement of intestinal blood circulation. Further, our applied combined approach showed a favorable outcome in mesenteric thrombosis patients and reduced the mortality rate by improving the prognosis significantly.

Novel mitochondrial targeting charge-reversal polysaccharide hybrid shell/core nanoparticles for prolonged systemic circulation and antitumor drug delivery.

Stability in systemic circulation, effective tumor accumulation, and the subsequent crucial subcellular targeting are significant elements that maximize the therapeutic efficacy of a drug. Accordingly, novel nanoparticles based on polysaccharides that simultaneously presented prolonged systemic circulation and mitochondrial-targeted drug release were synthesized. First, the mitochondrial-targeted polymer, 3,4-dihydroxyphenyl propionic acid-chitosan oligosaccharide-dithiodipropionic acid-berberine (DHPA-CDB), was synthesized, which was used to form self-assembled curcumin (Cur)-encapsulated cationic micelles (DHPA-CDB/Cur). Negatively charged oligomeric hyaluronic acid-3-carboxyphenylboronic acid (oHA-PBA), a ligand to sialic acid and CD44, was further added to the surface of the preformed DHPA-CDB/Cur core to shield the positive charges and to prolong blood persistence. oHA-PBA@DHPA-CDB/Cur formed a covalent polyplex of oHA-PBA and DHPA-CDB/Cur via the pH-responsive borate ester bond between PBA and DHPA. The mildly acidic tumor environment led to the degradation of borate ester bonds, thereby realizing the exposure of the cationic micelles and causing a charge reversal from -19.47 to +12.01 mV, to promote cell internalization and mitochondrial localization. Compared with micelles without the oHA-PBA modification, the prepared oHA-PBA@DHPA-CDB/Cur showed enhanced cytotoxicity to PANC-1 cells and greater cellular uptake via receptor-mediated endocytosis. oHA-PBA@DHPA-CDB/Cur was effectively targeted to the mitochondria, which triggered mitochondrial membrane depolarization. In mice xenografted with PANC-1 cells, compared with control mice, oHA-PBA@DHPA-CDB/Cur resulted in more effective tumor suppression and greater biosafety with preferential accumulation in the tumor tissue. Thus, the long-circulating oHA-PBA@DHPA-CDB/Cur, with mitochondrial targeting and tumor environment charge-reversal capabilities, was shown to be an excellent candidate for subcellular-specific drug delivery.

Outcomes and clinical characteristics of transmural intestinal necrosis in acute mesenteric ischemia.

Background: Acute mesenteric ischemia (AMI) is a rare life-threatening condition, especially for the patients with transmural intestinal necrosis (TIN). However, the optimal time for surgical intervention is controversial. As a series study, this study aimed to identify the outcomes and clinical characteristic of patients with TIN. Methods: Clinical data of 158 patients with AMI from January 2010 to December 2017 were retrospectively analyzed in a national gastrointestinal referral center in China to confirm the outcomes and identify predictors for TIN. Results: According to the results of pathological assessment and follow-up, 62 patients were TIN and 96 were non-TIN. Patients with TIN have a higher mortality and incidence of severe complications. The significant independent predictors for TIN were arterial lactate level (OR: 4.76 [2.29 ∼ 9.89]), free intraperitoneal fluid (OR: 9.49 [2.56 ∼ 35.24]) and pneumatosis intestinalis (OR: 7.08 [1.68 ∼ 29.82]) in computed tomography (CT) scan imaging. The overall area under the receiver operating characteristics (ROC) curve of the model was 0.934 (95% confidence interval: 0.893 ∼ 0.974). Using ROC curve, the cutoff value of arterial lactate level predicting the onset of TIN was 2.65 mmol/L. Conclusions: Patients concomitant with TIN manifest a higher risk of poor prognosis. The three predictors for TIN were arterial lactate level >2.65 mmol/L, free intraperitoneal fluid and pneumatosis intestinalis. Close monitoring these predictors would help identify AMI patients developed TIN and in urgent need for bowel resection.