A model for preservation of thymocyte-depleted thymus

DiGeorge syndrome is a disorder caused by a microdeletion on the long arm of chromosome 22. Approximately 1% of patients diagnosed with DiGeorge syndrome may have an absence of a functional thymus, which characterizes the complete form of the syndrome. These patients require urgent treatment to reconstitute T cell immunity. Thymus transplantation is a promising investigational procedure for reconstitution of thymic function in infants with congenital athymia. Here, we demonstrate a possible optimization of the preparation of thymus slices for transplantation through prior depletion of thymocytes and leukocyte cell lineages followed by cryopreservation with cryoprotective media (5% dextran FP 40, 5% Me2SO, and 5% FBS) while preserving tissue architecture. Thymus fragments were stored in liquid nitrogen at -196°C for 30 days or one year. The tissue architecture of the fragments was preserved, including the distinction between medullary thymic epithelial cells (TECs), cortical TECs, and Hassall bodies. Moreover, depleted thymus fragments cryopreserved for one year were recolonized by intrathymic injections of 3×106 thymocytes per mL, demonstrating the capability of these fragments to support T cell development. Thus, this technique opens up the possibility of freezing and storing large volumes of thymus tissue for immediate transplantation into patients with DiGeorge syndrome or atypical (Omenn-like) phenotype.

Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells

While Mek1/2 and Gsk3β inhibition ("2i") supports the maintenance of murine embryonic stem cells (ESCs) in a homogenous naïve state, prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential. Additionally, 2i fails to support derivation and culture of fully potent female ESCs. Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin (AlbuMAX) undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture. Mechanistically, lipids in AlbuMAX impact intracellular metabolism including nucleotide biosynthesis, lipid biogenesis, and TCA cycle intermediates, with enhanced expression of DNMT3s that prevent DNA hypomethylation. Lipids induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation, which also alleviates X chromosome loss in female ESCs. Importantly, both male and female "all-ESC" mice can be generated from de novo derived ESCs using AlbuMAX-based media. Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.

Treatment of Psoriasis Based on Theory of Ascending and Descending of Center Qi / 中医杂志

Based on the theory of ascending and descending of center qi， it is believed that yang deficiency and water dampness， as well as abnormal circulation of center qi， are the core pathogenesis of psoriasis. The common pathogenic evolution of psoriasis includes wood constraint and blood stagnation， lung metal fluid exhaustion. In the later stage of psoriasis， a mixture of deficiency and excess patterns， as well as cold and heat in complexity， are often observed. Treatment focuses on warming yang and resolving dampness to restore proper qi ascending and descending， and the therapeutic formulas such as Ganjiang Lingzhu Decoction （甘姜苓术汤）， Zexie Decoction （泽泻汤）， Zhenwu Decoction （真武汤）， and Linggui Zhugan Decoction （苓桂术甘汤） are suggested based on the nature and location of the disease. To unblock the qi movement through discharging the liver and rectifying the lung， Xiaochaihu Decoction （小柴胡汤） and Danzhi Xiaoyao Powder （丹栀逍遥散） are commonly used as the foundation with modifications. To balance yin and yang through clearing the heart and nourishing the kidneys， a self-designed Changzhong Decoction （畅中汤） is utilized. Following the theory of ascending and descending of center qi， it is suggested to combine cold and warm medicinals and mediate the center earth， so as to promote the circulation of the center qi， restore the clear and the turbid， and keep four-dimensional smooth flow of qi， providing a reference for traditional Chinese medicine treatment for psoriasis.

The influencing factors of functional somatic discomfort in clinical nurses / 中华劳动卫生职业病杂志

Objective: To investigate the functional somatic discomfort status, and to analyze the effect of job stress, hostile attribution bias and ego depletion on functional somatic discomfort in clinical nurses. Methods: In May 2019, 10 cities in Henan Province and Fujian Province were randomly selected as sampling cities. Using the stratified cluster sampling method, nurses of clinical nursing posts in 22 third class hospitals and 23 second class hospitals were selected as the research objects. The general information, job stress, hostile attribution bias, ego depletion and functional somatic discomfort of clinical nurses were investigated by self-designed general information questionnaire, Perceived Stress Scale, Social Information Processing-attribution Bias Questionnaire, Self-regulatory Fatigue Scale, Patient Health Questionnaire-15. 1200 clinical nurses included, and a total of 1159 valid questionnaires were collected, the effective rate of questionnaire collection was 96.6%. The t test was used to compare the difference of the functional somatic discomfort scores of clinical nurses with different demographic characteristicst. The influence of job stress, hostile attribution bias and ego depletion on functional somatic discomfort of clinical nurses were analyzed with Bootstrap. Results: The functional somatic discomfort score of clinical nurses was (8.95±4.38), of which 859 (74.12%) had functional somatic discomfort symptom. The functional somatic discomfort score of clinical nurses aged 36-50 years old was higher than that of 19-35 years old, the functional somatic discomfort score of clinical nurses with service age ≥5 years was higher than that of <5 years, the functional somatic discomfort score of non-permanent clinical nurses was higher than that of permanent clinical nurses, the functional somatic discomfort score of clinical nurses in tertiary hospitals was higher than that of secondary hospitals, the functional somatic discomfort score of clinical nurses in surgical departments were higher than those in non-surgical departments, and the differences were statistically significant (P<0.05). Job stress affected functional somatic discomfort through the single mediating role of hostile attribution bias, the single mediating role of ego depletion, and the chain mediating role of hostile attribution bias and ego depletion (β=0.17, 95%CI: 0.10-0.20; β=0.16, 95%CI: 0.10-0.20; β=0.07, 95%CI: 0.03-0.10; P<0.05) . Conclusion: The functional somatic discomfort symptoms of clinical nurses are significant and varied among different age, working age, employment form, hospital grade and department groups. They are affected by work stress directly and through the separate mediating effect of hostile attribution bias and ego depletion, and the chain mediating effect of hostile attribution bias and ego depletion.

Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing

Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

Frontiers and development in live-cell super-resolution fluorescence microscopy / 生物医学工程学杂志

This paper reviews the research progress on live-cell super-resolution fluorescence microscopy, discusses the current research status and hotspots in this field, and summarizes the technological application of super-resolution fluorescence microscopy for live-cell imaging. To date, this field has gained progress in numerous aspects. Specifically, the structured illumination microscopy, stimulated emission depletion microscopy, and the recently introduced minimal photon fluxes microscopy are the current research hotspots. According to the current progress in this field, future development trend is likely to be largely driven by artificial intelligence as well as advances in fluorescent probes and relevant labelling methods.

Elderly Neurogenic Orthostatic Hypotension Treated Mainly with Fire Needling on Governor Vessel （督 脉）：A Case Report / 中医杂志

Neurogenic orthostatic hypotension （nOH） is a common neurodegenerative disease， and is usually differentiated as kidney-yang depletion syndrome in traditional Chinese medicine （TCM）. Fire needling on governor vessel （督脉） acupoints as well as Shenshu （BL 23） and Zhishi （BL 52） can dredge the qi and blood of governor vessel， so as to warm yang and unblock the channels， supplement essence and boost marrow. A case of elderly nOH treated by fire needling mainly at governor vessel points， Shenshu （BL 23） and Zhishi （BL 52） was reported. After nearly two months of treatment， the patient's orthostatic blood pressure difference and yang deficiency-related symptoms were significantly improved， and the results of blood pressure monitoring， TCM syndrome scale evaluation and Shenshu （BL 23） area infrared imager detection all showed definite clinical effect.

Research progress on the oxygen depletion hypothesis of ultra-high dose rate radiotherapy / 中华放射肿瘤学杂志

In recent years, ultra-high dose rate (FLASH) radiotherapy has become one of the most advanced research topics in the field of radiotherapy. Experimental data indicate that FLASH radiotherapy can significantly reduce the irradiation damage in normal tissues while being as effective as clinical conventional dose rate radiotherapy in tumor control. The oxygen depletion hypothesis is considered as one of the key mechanisms underlying the FLASH effect. In this article, research progress on the discovery, experimental evidence and reaction principle of oxygen depletion was reviewed, the measurement methods and biological effect modeling methods of the oxygen depletion hypothesis were summarized, and the oxygen depletion difference between normal tissue and tumor was also discussed.

Association of Ego-depletion level with glycemic control and quality of life among adolescents with type 1 diabetes / 中国实用护理杂志

Objective:To investigate the ego-depletion level of adolescents with type 1 diabetes mellitus (T1DM) and to explore its association with glycemic control and quality of life.Methods:This was a cross-sectional survey study. A total of 195 adolescents with T1DM were recruited from the First Affiliated Hospital of Nanjing Medical University from March to September 2022 by convenient sampling method. The Self-Regulatory Fatigue Scale (SRF-S) and Short Form of the Chinese version Diabetes Quality of Life for Youth Scale (C-DQOLY-SF) and the general information questionnaire were collected and the glycated hemoglobin (HbA 1c) value was detected. Results:The total score of self-regulatory fatigue for 195 adolescents with T1DM was (42.23 ± 9.94) points, with a scoring rate of 52.79%, which was at a medium level. Pearson correlation analysis showed that the total score of self-regulatory fatigue was positively correlated with HbA1c ( r = 0.25, P<0.01), and negatively correlated with quality of life ( r = -0.61, P<0.01). The hierarchical linear regression results showed that after controlling for demographic sociolagy and disease variables, ego-depletion had a positive predictive effect on HbA1c ( t = 3.69, P<0.01), while ego-depletion had a negative predictive effect on Quality of life ( t = -8.48, P<0.01). Conclusions:Ego-depletion of adolescents with T1DM may affect their blood glucose control and quality of life, which should be noticed by medical workers.

Depleción de eosinófilos: muchas implicaciones en modelos múridos, pocas estudiadas en humanos / Eosinophil depletion: many implications in murine models, few studied in humans

The eosinophil is a cell of the immune system, with an arsenal of substances that can alter the balance that exists in the different organs where they are found. With the advent of monoclonal antibodies, concern about their depletion has become an important turning point in their formulation. For this reason, it is of vital importance to investigate the consequences of the mechanism of action of biological agents, in the short and long term. This review tries to show the role of eosinophils in both homeostasis and disease, and their relationship and interaction with monoclonal drugs in diseases focused on the Th2 profile. It is expected that this article can be useful when making the decision to start treatment with monoclonals, specifically anti-interleukin-5 or against its receptor

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

The influence of workplace violence on burnout sense in clinical nurses / 中华劳动卫生职业病杂志

Objective: To explore the influence mechanism of intrusive thoughts and ego depletion between effects of workplace violence on burnout sense in clinical nurses. Methods: In May 2019, 10 cities in Henan Province and Fujian Province were selected as sampling cities by the method of grabbing random balls. Using the stratified cluster sampling method, nurses in clinical nursing posts in 22 third class hospitals and 23 second class hospitals were selected as the research objects for a cross-sectional epidemiological survey, including 1200 nurses. A total of 1159 valid questionnaires were collected, and the effective rate was 96.6%. 1159 clinical nurses were investigated by workplace violence scale, event impact scale, self-regulation fatigue scale and job burnout scale. The items contained in the questionnaire were analyzed by exploratory factor analysis with Harman single factor test, and the demographic characteristics of nurses' workplace violence, invasive thinking, self loss and job burnout were compared and analyzed with s-n-k. Results: Those with less than 3 years of service, those with more than 3 years of aggressive thinking and self loss score, and those with less than 3 years of job burnout score; The score of job burnout of unmarried was lower than that of married; The scores of invasive thinking and self loss of non editors were higher than those of current editors; The scores of workplace violence, aggressive thinking, self loss and job burnout of clinical nurses in tertiary hospitals were higher than those in secondary hospitals; The score of job burnout of undergraduate and above is higher than that of junior college and below; The scores of workplace violence, aggressive thinking and self loss of clinical nurses in surgical departments were higher than those in non-surgical departments; The job burnout score of those aged 36 and above was higher than that of those aged <36, The difference was statistically significant (P< 0.05) . Aggressive thinking and self attrition played a mediating role between workplace violence and job burnout. Workplace violence affected job burnout through the single mediating role of aggressive thinking, the single mediating role of self attrition, and the chain mediating role of aggressive thinking self attrition (β=0.16、0.08、0.03, 95%CI: 0.251~0.190、0.121~0.028、0.050~0.012, P<0.05) . Conclusion: Workplace violence affects burnout sense through the independent mediating role of intrusive thoughts and ego depletion and the chain mediating role of intrusive thoughts and ego depletion in clinical nurses.

Effect of childhood trauma on depressive symptoms in college students: the mediating role of depletion sensitivity and the moderating role of self-control / 中华行为医学与脑科学杂志

Objective:To explore the effects of childhood trauma on depression of college students and the role of depletion sensitivity and self-control in it.Methods:A total of 1 678 freshmen and sophomores from a medical university in Guangzhou were investigated by childhood trauma questionnaire(CTQ), Beck depression inventory-Ⅱ(BDI-Ⅱ), depletion sensitivity scale(DSS) and self-control scale(SCS) through random cluster sampling. The mediating effect of depletion sensitivity and moderating effect of self-control were examined by SPSS 26.0 macro program PROCESS V2.13.Results:(1)The total scores of CTQ and BDI-Ⅱ in college students were (34.56±7.03) and ( M( QR): 5.00(7.00)) respectively, and the scores of DSS and SCS were (41.78±12.21) and (40.02±8.15) respectively. (2)Childhood trauma was positively correlated with depletion sensitivity ( r= 0.20, P<0.01) and depletion sensitivity was positively correlated with depressive symptoms ( r=0.48, P<0.01). There was a negative correlation between self-control and depressive symptoms ( r=-0.49, P<0.01). (3)Depletion sensitivity partly mediates the relationship between childhood trauma and depressive symptoms. The direct effect (effect size=0.28) and mediating effect (effect size=0.07) accounted for 80% and 20% of the total effect (effect size=0.35), respectively. (4)Self-control moderated the path between depletion sensitivity and depressive symptoms. Conclusion:Childhood trauma can indirectly affect college students′ depressive symptoms through depletion sensitivity, and the partial mediatory role of depletion sensitivity is also moderated by self-control.

Research progress of ego-depletion in patients of chronic diseases / 中国实用护理杂志

Ego-depletion is a phenomenon in which an individual's cognitive, emotional and behavioral control ability or willingness declines after long-term self-control. Patients with chronic diseases need to change their lifestyles for a long time, understand and master the knowledge of the disease, and they are prone to self-depletion after diagnosis. This paper summarized the research progress of ego-depletion in patients with chronic diseases through the concept of ego-depletion, subjective measurement tools, and the current research status of ego-depletion in patients with chronic diseases, and provided inspiration for future research directions, with a view to providing ideas for further research on ego-depletion in patients with chronic diseases.

A smart MnO

The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO

Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer chemodynamic/photothermal/chemo therapy

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS

Respuesta inmune disfuncional en pacientes con COVID-19. ¿Qué nos dice la evidencia? / Dysfunctional immune response in COVID-19 patients. What does the evidence tell us?

In December 2019 a novel coronavirus (SARS-CoV-2) was identified in Wuhan, China, and became rapidly the worst pandemic in 100 years. Coronaviruses are respiratory viruses that can cause diseases ranging from mild to fatal lower respiratory tract infections. In a fraction of the affected patients, coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, can lead to acute respiratory distress syndrome (ARDS) and intensive care unit (ICU) admission, both associated with high mortality. To date, the existing evidence suggests a leading role of the immune system in the pathogenesis of severe COVID-19, including mechanisms associated with hyperinflammation, immune evasion, cytokine release syndrome, depletion of functional T cells, and ineffective humoral immunity. Here we discuss the current evidence regarding these findings.

Muscle depletion in cirrhotic patients assessed using computed tomography: a cross-sectional study

ABSTRACT BACKGROUND: Sarcopenia is a common complication in patients with cirrhosis and may lead to increased morbidity and mortality. OBJECTIVE: To investigate the prevalence of sarcopenia and its association with disease severity scores, among patients with cirrhosis. DESIGN AND SETTING: Observational and retrospective cohort study carried out in a tertiary-care hospital in southern Brazil. METHODS: This study was conducted among patients with chronic liver disease who were followed up at the gastroenterology and hepatology outpatient clinic of a tertiary-care hospital in southern Brazil and who underwent computed tomography scans of the abdomen through any indication. RESULTS: We included 83 patients in the study. In the population evaluated, there was a predominance of males (57.80%) and the mean age was 56 years. Hepatitis B or C virus was present in the genesis of the disease in 34.9% of the cases, followed by an etiology of alcohol abuse (30.1%). Sarcopenia was diagnosed in 41 (49.4%) of the patients when the cutoff point for cirrhotic patients was used. There was no significant correlation between the Child-Pugh and MELD severity scores and the occurrence of sarcopenia. CONCLUSION: Sarcopenia presents high prevalence among patients with chronic liver disease, without any association with predictors of severity.

Predictors of the Response to an Epidural Blood Patch in Patients with Spinal Leakage of Cerebrospinal Fluid