Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.

Tunable intrinsic strong light-matter coupling in transition metal dichalcogenide nanoresonators.

Self-hybridizing structures based on transition metal dichalcogenides (TMDCs) are becoming promising candidates for the study of an intrinsic strong light-matter coupling because of the efficient mode overlap with much simplified geometries. However, realizing flexible tuning of intrinsic strong coupling in such TMDC-based structures is still challenging. Here, we propose a strategy for flexible tuning of the intrinsic strong light-matter coupling based on a bulk TMDC material. We report the first demonstration of the strong coupling of intrinsic excitons to whispering gallery modes (WGMs) supported by an all-TMDC nanocavity. Importantly, by simply controlling angles of incidence, a selective excitation of WGMs and an anapole can be realized, which enables a direct modulation of self-hybridized interactions from a bright WGM-exciton coupling to a dark anapole-exciton coupling. Our work is expected to provide unique opportunities for engineering a strong light-matter coupling and to open exciting avenues for highly integrated novel nanophotonic devices.

Role of mitochondria-associated membranes in the hippocampus in the pathogenesis of depression.

BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.

Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosis of synapses in a mouse model of depression.

BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.

Development and validity of a mentally-passive and mentally-active sedentary time questionnaire in nursing college students.

Objective: This study aimed to develop and validate a questionnaire to evaluate nursing college students' mentally-passive and mentally-active sedentary time (M-PAST) in China. Methods: An initial M-PAST questionnaire with mentally-passive and mentally-active sedentary behaviors was developed with content validity undertaken through a consensus panel and pilot test where a convenience sample of six nursing students was recruited to assess the relevance, comprehensiveness, and comprehensibility of the refined questionnaire after expert panelists' responses. A cross-sectional online survey using a self-reported questionnaire was distributed to nursing students by email and then conducted using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to assess the construct validity of the M-PAST questionnaire and factor structures. Finally, the criterion validity was examined by exploring the associations between the M-PAST and the IPAQ sitting time, psychological distress, and insomnia. Results: Eight items regarding learning and leisure were included in the final version of the M-PAST questionnaire. A group of 650 nursing college students in China completed the study. Principal component analysis revealed two factors (i.e., mentally-passive and mentally-active sedentary behaviors), which explained 41.98% of the variance contributing to the questionnaire. The CFA reached the adaptive standard. Cronbach's α ranged from 0.730 to 0.742. The correlations between M-PAST and IPAQ total sitting time were significant (p < 0.01, r = 0.125-0.396). Mentally-passive sedentary time was associated with psychological distress and insomnia (p < 0.01, r = 0.078-0.163), while no significant associations were found in mentally-active sedentary behaviors. Conclusion and implications for practice: The M-PAST questionnaire appears to be a reliable and valid tool that reported both mentally-passive and mentally-active sedentary behaviors in nursing college students in China. However, future studies may need to further examine its validity among international nursing college students. This study further confirmed that mentally-passive sedentary behavior was positively associated with psychological distress and insomnia. Effective strategies are needed to reduce nursing college students' mentally-passive sedentary time to improve their health and wellbeing in China.

Toward Antifragility: Social Defeat Stress Enhances Learning and Memory in Young Mice Via Hippocampal Synaptosome Associated Protein 25.

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.

LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors.

Background: Only a fraction of lung adenocarcinoma (LUAD) patients are eligible for immunotherapy. The identification of biomarkers for immunotherapy is crucial to improve patient outcomes. This study aims to systemically analyze LRP1B mutation and its association with the tumor immune microenvironment (TIME) and immunotherapy. Methods: A cohort of immune checkpoint inhibitors (ICIs)-treated LUAD patients was analyzed to assess the association of LRP1B mutation with immunotherapy prognosis. Another cohort of LUAD patients with genetic and transcriptomic data was also obtained from The Cancer Genome Atlas (TCGA). By investigating the ICIs and the TCGA-LUAD cohorts, we compared the differences in mutation profiles, immunogenicity, TIME, and DNA damage repair (DDR) mutations between the LRP1B-mutated and LRP1B wild-type groups. Additionally, we performed multiplex immunohistochemistry (mIHC) to validate the differences in the tumor microenvironment. Results: Our results revealed that LRP1B mutation is associated with multiple immune-related pathways. Analysis of TIME indicated that LUAD patients with LRP1B mutation expressed significant levels of genes involved in antigen presentation, cytotoxicity, chemokines, and pro-inflammatory mediators, whereas a few immune checkpoint genes were highly expressed in the LRP1B-mutated group as well. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis indicated that LRP1B-mutated LUAD patients had higher infiltration of active immune cells. Multiplex IHC analysis showed that LRP1B-mutated LUAD patients had elevated programmed death ligand-1 (PD-L1) expression and immune cell infiltration. Patients with LRP1B mutation had higher tumor mutation burden, neoantigens, as well as more mutated genes in the DDR-related pathways. Finally, LRP1B-mutated LUAD patients showed a significant prolongation of progression-free survival (PFS) in the ICIs cohort and could be effectively predicted by our constructed nomogram. Conclusions: Our study suggests that LRP1B mutation is associated with higher immune cell infiltration and elevated immune gene expression in TIME and potentially serves as a prognostic biomarker for LUAD patients treated with ICIs.

Fast carrier diffusion via synergistic effects between lithium-ions and polarons in rutile TiO2.

Carrier mobility in titanium dioxide (TiO2) systems is a key factor for their application as energy materials, especially in solar cells and lithium-ion batteries. Studies on the diffusion of Li-ions and polarons in rutile TiO2 systems have attracted extensive attention. However, how their interaction affects the diffusion of Li-ions and electron polarons is largely unclear and related studies are relatively lacking. By using first-principles calculations, we systematically investigate the interaction between the intercalated Li-ions and electron polarons in rutile TiO2 materials. Our analysis shows that the diffusion barrier of the electron polarons decreases around the Li-ion. The interaction between the Li-ions and polarons would benefit their synergistic diffusion both in the pristine and defective rutile TiO2 systems. Our study reveals the synergistic effects between the ions and polarons, which is important for understanding the carrier properties in TiO2 systems and in further improving the performance of energy materials.

Huashi baidu granule in the treatment of pediatric patients with mild coronavirus disease 2019: A single-center, open-label, parallel-group randomized controlled clinical trial.

Background: Since late February 2022, a wave of coronavirus disease 2019 (COVID-19) mainly caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China. Traditional Chinese medicine treatment is recommended for pediatric patients; however, the safety and efficacy remain to be confirmed. We conducted a single-center, open-label, parallel-group randomized controlled trial to assess the efficacy and safety of a Chinese herb compound, Huashi Baidu granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. Methods: 108 recruited children (aged 3-18 years) with laboratory-confirmed mild COVID-19 were randomly allocated 2:1 to receive oral HSBDG for five consecutive days (intervention group) and to receive compound pholcodine oral solution for five consecutive days (control group). The negative conversion time of SARS-CoV-2 nucleic acid and symptom scores were recorded. Results: The median negative conversion time of SARS-CoV-2 nucleic acid was significantly shorter in the intervention group than in the control group (median days [interquartile range (IQR)]: 3 [3-5] vs. 5 [3-6]; p = 0.047). The median total symptom score on day 3 was significantly lower in the intervention group than in the control group (median total symptom score [IQR]: 1 [0-2] vs. 2 [0-3]; p = 0.036). There was no significant differences in the frequency of antibiotic use and side effects between the two groups. Conclusion: HSBDG is a safe, effective oral Chinese herbal compound granule, which shows a good performance within the Omicron wave among pediatric patients.

A Latent Profile Analysis of PERMA: Associations with Physical Activity and Psychological Distress among Chinese Nursing College Students.

Background: The wellbeing of college students is an important concern for public health, and may have associations with insufficient physical activity and psychological distress. This study aimed to identify the latent classes of wellbeing based on the PERMA (i.e., positive emotions, engagement, relationships, meaning, and accomplishments) wellbeing framework, and to explore their associations with levels of physical activity and psychological distress. Methods: A cross-sectional online survey was conducted. A latent profile analysis was performed to characterize the different classes of wellbeing of nursing college students. Results: A group of 1741 nursing college students in China completed the study. Three wellbeing classes were identified in the final model (i.e., low-level wellbeing, moderate-level wellbeing, and high-level wellbeing). Significant differences were found between the three classes in terms of gender (p = 0.002) and year of study (p = 0.038). Low levels of physical activity participation were significantly associated with lower odds of being in the high-level wellbeing class compared with the moderate-level wellbeing class (OR = 1.398, 95%CI [1.023, 1.910], p = 0.035). Lower levels of psychological distress were also associated with greater wellbeing among the three wellbeing classes (p < 0.05). Conclusions: Effective strategies are needed to increase college students' physical activity participation and decrease the severity of psychological distress to improve their health and wellbeing in China.

Sirtuin 3 Plays a Critical Role in the Antidepressant- and Anxiolytic-like Effects of Kaempferol.

An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.

Minocycline alleviates abnormal microglial phagocytosis of synapses in a mouse model of depression.

BACKGROUND: As antidepressants commonly used in the clinic have proved to be problematic, it is urgent to gain an updated understanding of the pathogenesis of depression and find potential therapeutic targets. Since both functional brain imaging studies and autopsy reports indicated that there is indeed a loss of synapses in depressed patients, it is necessary to explore the mechanism of this process. METHODS: We firstly investigated the effect of chronic social defeat stress (CSDS), a mouse model of depression, on behaviors, synapses, microglia, and microglial phagocytosis of synapses in mice. Then, as it is unclear whether microglial phagocytosis leads to synaptic loss, or synaptic loss induces the microglial clearance in CSDS mice, we used minocycline, a microglial activation inhibitor, to inhibit the microglial phagocytosis of synapses and study its effect on synapses and behaviors in CSDS mice. RESULTS: Our results showed that the expression levels of PSD-95 in the hippocampal dentate gyrus (DG) of CSDS mice were significantly reduced, while the microglia were significantly activated and the Iba1+CD68+ cell (phagocytic microglia) density was increased. We co-labeled the synaptic protein PSD-95 with the microglia marker Iba1 and found that the microglia in the hippocampal DG of CSDS mice contained significantly more PSD-95 engulfed puncta, which revealed that microglia in CSDS mice abnormally phagocytized synapses. Moreover, our results indicated that minocycline treatment dampened microglial activation, decreased the phagocytic microglia density, reduced abnormal microglial phagocytosis of synapses, reversed synaptic loss, and alleviated behavioral impairment in CSDS mice. CONCLUSIONS: Under depressive pathological conditions, the activated microglia may abnormally engulf neuronal synapses causing synaptic loss and behavioral impairments. Thus, microglial phagocytosis may be a novel therapeutic target for the treatment of depression.

Predicting the risk of axillary lymph node metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features and the use of nomograms: a prospective single-center observational study.

OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.

Combination of NSAIDs with donepezil as multi-target directed ligands for the treatment of Alzheimer's disease.

To search for multi-target directed ligands for the treatment of Alzheimer's disease (AD), eight hybrid compounds from the combination of non-steroidal anti-inflammatory drugs with donepezil were designed and synthesized. The enzyme test revealed that the synthesized compounds had remarkable inhibitory activity towards both AChE and BChE. The IC50 values of the most active compound 3a reached 0.015 and 0.80 µM for AChE and BChE, respectively, much lower than that of donepezil. Besides, the anti-inflammatory assays showed that the target compounds could effectively inhibit COX-1 and COX-2, and prevent the secretion of proinflammatory cytokines (TNF-α and IL-1ß) induced by LPS. Moreover, the target compound could also protect the neuron cells from the damage caused by Aß42 in vitro. All the results suggest that the hybrid compounds, in particular compound 3a, can be considered as potential candidates for the treatment of AD.

L-5-hydroxytryptophan promotes antitumor immunity by inhibiting PD-L1 inducible expression.

BACKGROUND: The repression or downregulation of programmed death-ligand 1 (PD-L1) can release its inhibition of T cells and activate antitumor immune responses. Although PD-1 and PD-L1 antibodies are promising treatments for diverse tumor types, their inherent disadvantages and immune-related adverse events remain significant issues. The development of small molecule inhibitors targeting the interaction surface of PD-1 and PD-L1 has been reviving, yet many challenges remain. To address these issues, we aimed to find small molecules with durable efficacy and favorable biosafety that alter PD-L1 surface expression and can be developed into a promising alternative and complementary therapy for existing anti-PD-1/PD-L1 therapies. METHODS: Cell-based screen of 200 metabolic molecules using a high-throughput flow cytometry assay of PD-L1 surface expression was conducted, and L-5-hydroxytryptophan (L-5-HTP) was found to suppress PD-L1 expression induced by interferon gamma (IFN-γ). Inhibition of PD-L1 induction and antitumor effect of L-5-HTP were evaluated in two syngeneic mouse tumor models. Flow cytometry was performed to investigate the change in the tumor microenvironment caused by L-5-HTP treatment. RESULTS: We discovered that L-5-HTP suppressed IFN-γ-induced PD-L1 expression in tumor cells transcriptionally, and this effect was directly due to itself. Mechanistically, L-5-HTP inhibited IFN-γ-induced expression of RTK ligands and thus suppressed phosphorylation-mediated activation of RTK receptors and the downstream MEK/ERK/c-JUN signaling cascade, leading to decreased PD-L1 induction. In syngeneic mouse tumor models, treatment with 100 mg/kg L-5-HTP (intraperitoneal) inhibited PD-L1 expression and exhibited antitumor effect. L-5-HTP upregulated the ratio of granzyme B+ CD8+ activated cytotoxic T cells. An intact immune system and PD-L1 expression was critical for L-5-HTP to exert its antitumor effects. Furthermore, L-5-HTP acted synergistically with PD-1 antibody to improve anticancer effect. CONCLUSION: Our study illustrated L-5-HTP's inhibitory effect on PD-L1 induction stimulated by IFN-γ in tumor cells and also provided insight into repurposing L-5-HTP for use in tumor immunotherapy.

The neuroprotective effects of GPR55 against hippocampal neuroinflammation and impaired adult neurogenesis in CSDS mice.

Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression.

Comparison of the Characteristics and Prognosis Between Very Young Women and Older Women With Breast Cancer: A Multi-Institutional Report From China.

Purpose: Our understanding of breast cancer in very young women (≤35 years old) remains limited. We aimed to assess the clinicopathological characteristics, molecular subtype, and treatment distribution and prognosis of these young patients compared with patients over 35 years. Methods: We retrospectively analyzed non-metastatic female breast cancer cases treated at three Chinese academic hospitals between January 1, 2008, and December 31, 2018. Local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were compared between different age groups and stratified with distinct molecular subtypes. Results: A total of 11,671 women were eligible for the final analyses, and 1,207 women (10.3%) were ≤35 years at disease onset. Very young breast cancer women were more likely to be single or childless, have higher-grade disease, have more probability of lymphovascular invasion (LVI) in tumor and triple-negative subtype, and be treated by lumpectomy, chemotherapy especially more anthracycline- and paclitaxel-based chemotherapy, endocrine therapy plus ovarian function suppression (OFS), anti-HER2 therapy, and/or radiotherapy than older women (P < 0.05 for all). Very young women had the lowest 5-year LRFS and DFS among all age groups (P < 0.001 for all). When stratified by molecular subtype, very young women had the worst outcomes vs. women from the 35~50-year-old group or those from >50-year-old group for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) subtype, including LRFS, DFS, and OS (P < 0.05 for all). In terms of LRFS and DFS, multivariate analyses showed similar results among the different age groups. Conclusion: Our study demonstrated that very young women with breast cancer had higher-grade tumors, more probability of LVI in tumor, and more triple-negative subtype, when compared with older patients. They had less favorable survival outcomes, especially for patients with the HR+/HER2- subtype.

CFD-PBM Simulation on Bubble Size Distribution in a Gas-Liquid-Solid Flow Three-Phase Flow Stirred Tank.

The bubble size distribution, location distribution, and gas holdup in a gas-liquid-solid flow three-phase stirred tank were numerically simulated by the Eulerian-Eulerian method and the population balance model (PBM). The Euler-Euler method combined with the PBM model included the influence of bubble aggregation and fragmentation on the interfacial force, which can better predict the bubble size distribution and phase holdups. The simulation results show that there are some differences in the fluid morphology and gas dispersion characteristics in the stirred tank under different rotating speeds. With the increase of rotating speed, the content of small-diameter bubbles increases obviously, and they are mainly concentrated in areas with higher speeds. The higher the rotational speed, the more the bubbles with small diameters, but the content of bubbles with large diameters is less affected by the rotational speed. Small-size bubbles mainly exist in the region of high fluid velocity, while large-size bubbles mainly exist in the region of low hydrostatic pressure. Compared with the change of the bubble content at different speeds, the content of bubbles with diameters of 0.50-1.90 mm is largest at 2000 rpm, while the content of bubbles with diameters of 2.65-10.09 mm is largest at 1500 rpm. The simulation work has certain guiding significance for the research and development of the forced mineralization device and the understanding of the dispersion characteristics of bubbles in the stirred tank.

Latent profiles of emotion regulation strategies associated with alexithymia, nonsuicidal self-injury and resilience among nursing students.

The present study sought to better understand the complex nature of emotion regulation in nursing students by exploring patterns of emotion regulation strategies (ERSs), and to examine the relationships between these unique profiles with alexithymia, nonsuicidal self-injury (NSSI) and resilience. A total of 1960 nursing students (Mage  = 19.56, SD = 1.13 years) were recruited. Using latent profile analysis, nursing students were classified into four profiles based on their ERS use: high reaction profile (HRP; 11.53%), medium reaction profile (MRP; 55.46%), adaptive reaction profile (ARP; 22.86%) and low reaction profile (LRP; 10.15%). This study found that relative to HRP and MRP, ARP and LRP showed a lower incidence of NSSI and alexithymia; HRP and ARP showed a higher level of resilience than MRP and LRP. Furthermore, LRP had the lowest level of resilience. This study highlights the importance of identifying the different ERS profiles among nursing students. Targeted programs are needed to enhance adaptive strategies and reduce maladaptive strategies to improve nursing students' psychological and behavioural performance.

Prognosis of bronchial asthma in children with different pulmonary function phenotypes: A real-world retrospective observational study.

Objective: To follow up on the changes in pulmonary function phenotypes in children with asthma in the first year after diagnosis, and explore the risk factors of poor control in children with good treatment compliance. Methods: Children who were diagnosed with asthma in the Respiratory Department of Shanghai Children's Medical Center from January 1, 2019 to December 31, 2020 and were re-examined every 3 months after diagnosis for 1 year were continuously included, regardless of gender. We collected the clinical data, analyzed clinical characteristics of the different pulmonary function phenotypes at baseline and explored risk factors of poor asthma control after 1 year of standardized treatment. Results: A total of 142 children with asthma were included in this study, including 54 (38.0%) with normal pulmonary function phenotype (NPF), 75 (52.8%) with ventilation dysfunction phenotype (VD), and 13 (9.2%) with small airway dysfunction phenotype (SAD) in the baseline. Among them, there were statistically significant differences in all spirometry parameters, age, and course of disease before diagnosis (P < 0.05), and a negative correlation between age (r 2 = -0.33, P < 0.001), course of disease before diagnosis (r 2 = -0.23, P = 0.006) and FEV1/FVC. After 1-year follow-up, large airway function parameters and small airway function parameters were increased, fractional exhaled nitric oxide (FeNO) was decreased, the proportion of NPF was increased, the proportion of VD was decreased (P < 0.05), while there was no significant difference in the proportion of SAD. After 1 year of standardized treatment, 21 patients (14.8%) still had partly controlled or uncontrolled asthma. Our results showed that the more asthma attacks occurred within 1 year (OR = 6.249, 95% CI, 1.711-22.818, P = 0.006), the more times SAD presented at baseline and Assessment 1-4 (OR = 3.092, 95% CI, 1.222-7.825, P = 0.017), the higher the possibility of incomplete control of asthma. Conclusion: About 15% of the children with good treatment compliance were still not completely controlled after 1 year of treatment, which is closely associated with persistent small airway dysfunction.