[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Clinimetric Properties of the Chinese Short Form of the Sarcopenia Quality of Life Questionnaire in Patients With Cancer.

BACKGROUND: Sarcopenia, prevalent in patients with cancer, negatively affects quality of life. However, generic tools are unable to capture the minor effects of sarcopenia on quality of life. The short-form version of the Sarcopenia Quality of Life (SF-SarQoL) questionnaire was developed as an efficient tool to assess the impact of sarcopenia on quality of life in older adults. However, its clinimetric properties in patients with cancer remain unknown. PURPOSE: This study was designed to examine the clinimetric properties of the Chinese SF-SarQoL in patients with colorectal cancer, particularly with regard to its ability to detect changes in quality of life. METHODS: A longitudinal survey was conducted using the SF-SarQoL and other questionnaires on 408 patients with colorectal cancer planning to undergo surgery. Follow-up was subsequently conducted on 341 of these patients 1 month after surgery. The clinimetric properties of the SF-SarQoL were examined, including reliability (internal consistency), validity (construct validity, concurrent validity), sensitivity (ability to detect changes, discriminative ability), and floor and ceiling effects. RESULTS: The internal consistency of the SF-SarQoL was found to be acceptable (Cronbach's alpha = .94 and McDonald's omega = .94). Strong scalability of the total score and each item was confirmed using Mokken analysis. Concurrent validity analyses indicate the SF-SarQoL is significantly correlated with muscle-related and health-related questionnaire scores. The SF-SarQoL showed adequate sensitivity due to its good ability to detect changes in quality of life with a moderate effect size (Cohen's d = 0.56) and discriminate between sarcopenic and nonsarcopenic patients (area under the curve = 0.73, 95% CI [0.66, 0.79]) using receiver operating characteristic curve analyses. No floor or ceiling effects were observed. CONCLUSIONS: The Chinese SF-SarQoL exhibits good clinimetric properties in preoperative patients with colorectal cancer and is sufficiently sensitive to capture changes in quality of life after surgery.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Relationship between anxiety and depressive trajectories of women who conceived through assisted reproductive technology and their children's emotional and behavioral problems: A prospective cohort study.

OBJECTIVE: This study aimed to examine the relationship between the anxiety and depressive trajectory of women conceived through assisted reproductive technology (ART) and their children's emotional and behavioral problems. METHODS: This prospective cohort study including 18,711 women, was conducted between July 2014 and December 2017. Self-rating scales for anxiety and depression were used before treatment, during the first trimester, and two to three years postpartum. A latent class growth analysis identified their maternal anxiety and depressive symptom trajectories. Multiple comparison and linear regression models were performed to assess the relationships between maternal trajectories and their offspring's emotional and behavioral problems. RESULTS: Three longitudinal heterogeneous trajectories of maternal anxiety and depressive symptoms were identified: resilient, recurrent, and emergent. After adjusting for covariates, children with mothers in the recurrent and emergent trajectory groups had higher Child Behavior Checklist/2-3 scores. Additionally, the participants with a recurrent trajectory had lower education and employment levels and younger maternal age at delivery. They also had a history of ovarian surgery, primipara, secondary infertility, polycystic ovary syndrome, and more embryo transferred cycles, including intracytoplasmic sperm injections. Those with resilient trajectories had higher antral follicle counts and GnRH antagonist protocol. Finally, the participants with emergent trajectories had a lower monthly income, primipara, ectopic pregnancy, and fresh embryo transfers. CONCLUSIONS: Infertile women's psychological stress was not alleviated by the ART-sociodemographic, infertility-related and treatment-related characteristics determined three mental health trajectories. Children with mothers in recurrent and emergent trajectories showed higher odds of experiencing emotional and behavioral problems.

Psychometric properties of the Chinese version of the Cognitive Reserve Assessment Scale in Health in patients with cancer.

BACKGROUND: Cognitive reserve is a modifiable factor that could prevent cognitive decline in patients with cancer. The Cognitive Reserve Assessment Scale in Health (CRASH) is an instrument used to assess cognitive reserve. This study aims to develop and examine the psychometric properties of the Chinese version of the CRASH for patients with cancer. METHODS: A cross-sectional survey was conducted with 167 cancer patients from four wards of two hospitals in China. Thirty-one patients were re-assessed to examine the test-retest reliability. Four translators and three reviewers developed the Chinese version of the scale. We assessed its structural validity, concurrent validity, internal consistency, test-retest reliability, measurement error, and floor/ceiling effects. RESULTS: Confirmatory factor analysis showed a good model fit with the four-factor structure of the original CRASH. The CRASH scores were statistically significantly associated with neuropsychological test scores, indicating sufficient concurrent validity. The internal consistency was acceptable, except for leisure activities, with standardized Cronbach's alphas (0.64-0.94) and standardized Omega (0.66-0.95). There was excellent test-retest reliability, with a high intraclass correlation coefficient (0.914-0.993) of total scores and scores for each domain. The measurement error was acceptable, and no floor or ceiling effects were observed. CONCLUSIONS: The Chinese version of the CRASH is a valid and reliable instrument to assess cognitive reserve in patients with cancer. Moreover, cognitive reserve measured by the CRASH was associated with low cognitive performance in cancer patients.

Sleep-related attentional bias: Development and validation of a Chinese version of the brief sleep-associated monitoring index in pregnant women.

OBJECTIVES: This study aimed to develop a Chinese version of the brief Sleep-Associated Monitoring Index (SAMI-B), and examine its psychometric properties among pregnant women. METHODS: This cross-sectional study conveniently recruited 665 pregnant women from two tertiary hospitals in Shandong, China; 110 completed a retest survey within two or three weeks after completing the baseline questionnaires. The scale was developed following established guidelines. Participants completed the SAMI-B, SAMI, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pre-Sleep Arousal Scale, Edinburgh Postnatal Depression Scale, and Generalized Anxiety Disorder-7 Scale. Psychometric evaluation included reliability (internal consistency, test-retest reliability) and validity (construct, item and concurrent validity; and diagnostic accuracy). RESULTS: The Chinese SAMI-B demonstrated uni-dimensionality construct, appropriate item fit and functioning; acceptable internal consistency (McDonald's ω = 0.917) and test-retest reliability (intraclass correlation = 0.736). It was significantly correlated with the SAMI (correlation coefficient = 0.765，P < 0.001) and other sleep-related measurements (correlation coefficients = 0.412-0.638, Ps < 0.001). The SAMI-B displayed a comparable area under the curve (0.739, 95% CI: 0.703-0.772) with the SAMI in detecting insomnia symptoms. The optimal cutoff point (18) presented a sensitivity of 0.765 and a specificity of 0.615 in distinguishing individuals with and without insomnia symptoms. After controlling for general information, the differences in the SAMI-B scores between those with or without insomnia symptoms remained significant (OR = 1.16, 95% CI: 1.12-1.20). CONCLUSION: The SAMI-B may be an effective alternative for clinicians and researchers to screen or track vulnerable individuals for prenatal insomnia symptoms.

Characteristics and subtypes of depressive symptoms in Chinese female breast cancer patients of different ages: a cross-sectional study.

PURPOSE: To identify the characteristics and subtypes of depressive symptoms and explore the relationship between depressive subtypes and age among Chinese female breast cancer patients. METHOD: In this cross-sectional study, 566 breast cancer patients were recruited from three tertiary comprehensive hospital in Shandong Province, China through convenient sampling from April 2013 to June 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Data analyses included descriptive analyses, latent class analysis. RESULTS: There were significant differences in specific depressive symptoms by age group, but no significant difference in total scores on PHQ-9. The depressive subtypes were severe (Class 4), relatively severe (Class 3; with lower psychomotor agitation/retardation and suicidal ideation), moderate (Class 2; with higher psychomotor agitation/retardation and suicidal ideation), and mild depressive symptoms (Class 1). The distribution of depression subtypes is different in various age groups. In the 45-59 age groups, severe symptoms subtype showed the highest ratios (i.e. 50.3%). CONCLUSION: This is the first study that analyses depressive symptom characteristics and identifies depressive subtypes in Chinese women with breast cancer across ages to explore symptom heterogeneity. Our findings can contribute to identifying the mechanisms behind these relationships and developing targeted interventions for patients with specific depressive subtypes.

Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins.

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.

Fear of future workplace violence and its influencing factors among nurses in Shandong, China: a cross-sectional study.

BACKGROUND: Fear of workplace violence has become a critical issue worldwide, which can lead to burnout, low levels of job satisfaction, and turnover. However, to date, little attention has been directed toward fear of workplace violence among nurses. Accordingly, this study investigated the level of fear of future workplace violence and its influencing factors among nurses in Shandong, China. METHODS: A cross-sectional study was conducted from July 30 through September 30, 2020 in Shandong Province, China. A total of 1898 nurses were enrolled from 12 tertiary hospitals. Fear of future workplace violence was measured using the Fear of Future Violence at Work scale. Demographic information, employment characteristics, social support, and experience of workplace violence were assessed. Multiple linear regression analysis was used to explore the influencing factors of fear of future workplace violence. RESULTS: The average score of fear of future violence at work was 67.43 ± 17.20 among nurses. Multiple linear regression analysis showed that higher fear of future violence at work scores were reported among nurses who were female (B = 7.10, p < 0.001), married (B = 3.50, p = 0.028), with a monthly income ≥5000 Chinese yuan (CNY) (B = 3.14, p = 0.007), working in the department of internal medicine (B = 2.90, p = 0.032), surgery (B = 5.03, p < 0.001), pediatrics (B = 5.38, p = 0.003), or emergency department (B = 4.50, p = 0.010), working as a contract employee (B = 2.41, p = 0.042), or who had experienced workplace violence (B = 7.02, p < 0.001). Lower fear of future violence at work scores were found among nurses who took vacations (1-14 days: B = - 2.52, p = 0.047; ≥15 days: B = - 3.69, p = 0.007) and had a high-level of social support (B = - 2.03, p = 0.020). CONCLUSIONS: There was a high level of fear of future workplace violence among nurses in Shandong, China. This should be considered an important issue by hospital administrators and government officials. Effective interventions need to be enacted to address the influencing factors of fear of future workplace violence.

Tissue factor-bearing microparticles are a link between acute promyelocytic leukemia cells and coagulation activation: a human subject study.

Acute promyelocytic leukemia (APL) cells constitutively express a large amount of tissue factor (TF) antigen, most of which is present in the cytoplasm. Coagulopathy may persist after induction therapy. We evaluated the overall role of circulating microparticles (MPs) in coagulation activation in APL-associated coagulopathy before and during induction therapy. Eleven adult patients with ≥ World Health Organization's (WHO) grade 2 bleeding events and 11 sex- and age-matched healthy controls were selected. All patients received arsenic trioxide alone as induction therapy. MP-associated TF (MP-TF) activity and MP procoagulant activity (MP-PCA) and 12 coagulation- and anticoagulation-associated indexes were measured before, during, and after induction therapy. Correlation between MP-associated indexes and the other 12 indexes was analyzed in patients. The MP-TF activity was negligible in controls, whereas it markedly increased in patients, dropped rapidly after treatment, and returned to normal at the end of induction therapy. The MP-PCA was similar between patients and controls. The correlation analysis revealed that TF-bearing MPs in patients mainly originated from APL cells. Partially differentiated APL cells could also release TF-bearing MPs, and the higher the degree of APL cell differentiation, the lower the ability of APL cells to release TF-bearing MPs. MP-TF was the main source of active TF in plasma and an important contributor for the coagulation activation in APL-associated coagulopathy. It was MPs released by APL cells/partially differentiated APL cells that served as the vehicle to transfer the large amount of TF to plasma to activate coagulation.

The efficacy and mechanisms of a guided self-help intervention based on mindfulness in patients with breast cancer: A randomized controlled trial.

BACKGROUND: Mindfulness-based interventions (MBIs) can alleviate psychological distress in patients with cancer. However, face-to-face MBIs may be inconvenient for patients. Therefore, guided self-help interventions may be more accessible. The authors investigated the effects of a guided self-help MBI for depression, anxiety, and sleep disorder symptoms in patients with breast cancer and explored the potential underlying mechanisms. METHODS: One hundred forty-four postoperative patients with breast cancer were randomly assigned to an intervention group (6-week guided self-help MBI; n = 72) or a wait-list control group (routine treatment; n = 72). Self-reported depression, anxiety, sleep disorder symptoms, and rumination and worry as potential mediators were assessed at baseline and postintervention. Outcomes were then assessed at 1-month and 3-month follow-up. The intervention's effects over time and the potential mediating effect were analyzed using generalized estimating equations. The trial was registered at the Chinese Clinical Registry (ChiCTR-IOR-16008073). RESULTS: Significant improvements in depression and sleep disorder symptoms occurred in the intervention group compared with wait-list controls, and the improvements were maintained at 1-month and 3-month follow-up. Changes in rumination and worry mediated the intervention's effects on changes in depression and sleep disorder symptoms. CONCLUSIONS: A guided self-help MBI reduced depressive and sleep disorder symptoms by mitigating rumination and worry in patients with breast cancer. These findings support benefits of this accessible psychological intervention in oncology and provide insight into possible mechanisms of action. The current research contributes to discovering effective and widely accessible means for people with physical health conditions and may remove barriers that otherwise would have precluded participation in face-to-face psychological interventions.

Magnetic nanoparticles: A new diagnostic and treatment platform for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by articular synovitis that eventually leads to the destruction of cartilage and bone in the joints with resulting pain and disability. The current therapies for RA are divided into 4 categories: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, nonbiological disease-modifying anti-rheumatic drugs (DMARDs), and biological DMARDs. Each drug grouping is beset with significant setbacks that not only include limited drug bioavailability and high clearance, but also varying degrees of drug toxicity to normal tissues. Recently, nanotechnology has provided a promising tool for the development of novel therapeutic and diagnostic systems in the area of malignant and inflammatory diseases. Among these, magnetic nanoparticles (MNPs) have provided an attractive carrier option for delivery of therapeutic agents. Armed with an extra magnetic probe, MNPs are capable of more accurately targeting the local lesion with avoidance of unpleasant systemic side effects. This review aims to provide an introduction to the applications of magnetic nanoparticles in RA, focusing on the latest advances, challenges, and opportunities for future development.

Perceived stress, anxiety, and depression in treatment-naïve women with breast cancer: a case-control study.

OBJECTIVE: Women with breast cancer face elevated risk for psychological problems. We aimed to examine to what extent treatment-naïve women with breast cancer are at higher risk for perceived stress and symptoms of anxiety and depression, compared with matched women with benign breast disease and healthy women, and explore the contribution of perceived stress in the association between breast cancer and symptoms of anxiety and depression. METHODS: The study included 360 women (120 per group). Perceived stress and symptoms of anxiety and depression were assessed using self-report questionnaires. We conducted linear and logistic regressions to assess increased risk and mediation analyses to test the role of perceived stress. RESULTS: After adjusting for potential confounders, perceived stress in women with breast cancer was 0.71 and 1.58 points higher than in patients with benign breast disease (p = 0.029) and healthy controls (p < 0.001), respectively; they were 1.85-2.44 times more likely to experience anxiety than either control group (p< 0.05) and 3.57 times more likely to experience depression than healthy controls (p < 0.001). The indirect effect of perceived stress between breast cancer and anxiety and depressive symptoms was 0.19-0.47 (p < 0.05). CONCLUSIONS: This study demonstrates the high risk of perceived stress and symptoms of anxiety and depression in treatment-naïve patients with breast cancer, and the association between breast cancer and increased anxiety and depressive symptoms through elevated perceived stress. It underscores the need to assess psychological status in pretreatment period and conduct stress-targeted prehabilitation interventions.

Cognitive reserve, modifiable-risk-factor profile and incidence of dementia: results from a longitudinal study of CFAS Wales.

OBJECTIVES: Both cognitive reserve and modifiable-risk-factor profiles play a role in dementia incidence. We investigated whether cognitive reserve moderates the risk of dementia attributable to the modifiable-risk-factor profile. METHOD: We followed 2102 older individuals aged 65+ years recruited from the population-based longitudinal cohort CFAS Wales study, begun in 2011, and the follow-up wave completed in early 2016. Cognitive reserve was measured by combining educational level, occupation complexity, and engagement in social and cognitive activities in later life. Modifiable-risk-factor profile scores were based on depression, diabetes, smoking, physical activity, healthy diet, and drinking. The interactions between cognitive reserve indicators and modifiable-risk-factor profiles were assessed on multiplicative and additive scales. RESULTS: There is an additive interaction between the composite effect of cognitive reserve indicator and modifiable-risk-factor profile on dementia. In those with low cognitive reserve, the risk of dementia in participants with a favorable profile was significantly lower than in those with an unfavorable one (OR = 0.08, 95% CI = 0.02-0.27). CONCLUSION: Cognitive reserve significantly moderates the association between modifiable-risk-factor profiles and dementia.

Association of Depressive Symptoms with Perceived Stress and Proinflammatory Cytokines in Treatment-Naïve Patients with Breast Cancer.

OBJECTIVES: This study aimed to explore the levels and associations among depressive symptoms, perceived stress, and proinflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) in treatment-naïve patients with breast cancer. METHODS: A cross-sectional study with one case and two control groups. Patients with breast cancer, matched patients with depression, and matched healthy women completed questionnaires and blood collection between May 2015 and March 2017. Data were analyzed using the general linear model and linear regression model. RESULTS: The severity of depressive symptoms and perceived stress among patients with breast cancer was significantly higher than that in healthy controls and lower than those in patients with depression. Interleukin-1ß was lower in patients with breast cancer than the other two groups. Perceived stress was independently and positively associated with depressive symptoms in patients with breast cancer. There were no significant associations between cytokines and depressive symptoms. CONCLUSION: Women with breast cancer experienced increased perceived stress prior to anticancer treatment, which was a strong contributor to severe symptoms of depression. Results emphasize the need to screen and identify patients with high perceived stress shortly after the disclosure of the diagnosis of breast cancer. Further research in larger sample is needed to investigate the relationship between proinflammatory cytokines and depressive symptoms.

Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. METHODS: ALL cell lines were treated with 1, 5 and 10 µM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. RESULTS: ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. CONCLUSIONS: The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

Association of renal function and depressive symptoms: Evidence from the China health and retirement longitudinal study.

AIM: We examined the association between kidney function and risks of depression in a nationally representative sample of community-dwelling older adults. METHODS: Participants were a subset selected from the China Health and Retirement Longitudinal Study. Estimated glomerular filtration rate (eGFR) was calculated using chronic kidney disease epidemiology collaboration equations. Incident depression was defined by a score of 10 or higher on the 10-item Center for Epidemiologic Studies Depression Scale, use of antidepressant medications, or both, at the 2015 follow-up visit. Multiple linear regression analyses were used to examine the baseline eGFR and CESD-10 score during follow up. The associations between level of renal function at baseline and incident depression were assessed using multivariate logistic regression analysis. RESULTS: Over a four-year follow-up period, 22.8% (N = 773) of the participants reported incident depression. After multivariate analysis, baseline eGFRcr and eGFRcr-cys were significantly associated with higher depression score during follow up. Coefficients and 95%CI for eGFRcr and eGFRcr-cys were - 0.041(-0.066 to -0.016) and - 0.028(-0.051 to -0.005), respectively. Using eGFRcr-cys, the crude odds ratio (OR) for incident depression in the 4th quartile group was 1.60 (95%CI 1.23-2.06) than that in the 1st quartile group, (p for trend <0.001). Fully adjustment for confounding factors did not attenuate but strengthened the association (OR 2.46, 95%CI 1.61-3.76). CONCLUSIONS: Among community-dwelling older adults over most of the range in renal function, eGFR was significantly, independently, and associated with incident depression.

Prospects of the Use of Cell Therapy to Induce Immune Tolerance.

Conditions in which abnormal or excessive immune responses exist, such as autoimmune diseases (ADs), graft-versus-host disease, transplant rejection, and hypersensitivity reactions, are serious hazards to human health and well-being. The traditional immunosuppressive drugs used to treat these conditions can lead to decreased immune function, a higher risk of infection, and increased tumor susceptibility. As an alternative therapeutic approach, cell therapy, in which generally intact and living cells are injected, grafted, or implanted into a patient, has the potential to overcome the limitations of traditional drug treatment and to alleviate the symptoms of many refractory diseases. Cell therapy could be a powerful approach to induce immune tolerance and restore immune homeostasis with a deeper understanding of immune tolerance mechanisms and the development of new techniques. The purpose of this review is to describe the current panoramic scope of cell therapy for immune-mediated disorders, discuss the advantages and disadvantages of different types of cell therapy, and explore novel directions and future prospects for these tolerogenic therapies.

Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients.

This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline data were collected from patients' electronic medical records. Patients' peripheral bloods, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. The rates of complete remission (CR), CR with minimal residual disease (MRD) negative/positive, and bridging to hematopoietic stem-cell transplantation (HSCT) were 92.3%, 76.9%, 15.4%, and 43.6%, respectively. The median event-free survival (EFS) was 11.6 months (95% confidence interval (CI): 4.0-19.2 months) and median overall survival (OS) was 14.0 months (95% CI: 10.9-17.1 months). Bridging to HSCT independently predicted better EFS and OS, while high bone marrow blasts level independently predicted worse EFS. The incidence of cytokine release syndrome (CRS) was 97.4%, and refractory disease as well as decreased white blood cell independently predicted higher risk of severe CRS. Other common adverse events included hematologic toxicities (grade I: 5.1%, grade II: 7.7%, grade III: 17.9%, grade IV: 69.2%), neurotoxicity (28.2%), infection (38.5%), and admission for intensive care unit (10.3%). In conclusion, CAR-T therapy presents with promising treatment response, survival and safety profiles, and higher disease burden predicts worse survival as well as increased risk of severe CRS in Chinese R/R B-ALL patients.

Physical frailty and the risk of major depressive disorder: The Irish Longitudinal Study on Ageing.

Although frailty is a well-established risk factor for adverse health outcomes in later life, little is known about the role of physical frailty on the development of incident major depressive disorder (MDD). The purpose of this study was to determine whether frailty is an important and independent predictor of incident major depressive disorder (MDD) in elderly people without probable depression at baseline. Of the 3671 older individuals from the population-based Irish Longitudinal Study on Ageing, we classified participants as non-frail (0), pre-frail (1-2), and frail (3-5) at baseline according to the five criteria of the physical frailty phenotype. The World Health Organization Composite International Diagnostic Interview Short-Form was used to assess whether respondents fulfilled the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for MDD over a 4-year follow-up. After adjusting for demographic factors, living arrangements, health behaviors, common chronic diseases including hypertension, diabetes, cancer, lung disease, heart problems, and stroke, those classified as pre-frail (HR = 1.40, 95%CI = 1.14-1.73) and frail (HR = 2.20, 95%CI = 1.23-3.92) presented a higher risk to develop incident MDD over the 4-year follow-up compared to non-frail participants. Shrinking and exhaustion, as physical frailty components, were individually predictive of onset of MDD. The present study supports a significant role of physical frailty as a predictor of incident MDD in older adults. It is necessary to identify groups with a high vulnerability for MDD according to easily identifiable frailty criteria, and to delay or prevent at least in part, some of the negative health outcomes related to this disorder.