Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×10⁹/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO₂ >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Vitamin B₁₂ deficiency, mostly of maternal origin in newborns, is a well treatable condition but can cause severe neurologic sequelae. In women of childbearing age and pregnant women worldwide vitamin B₁₂ deficiency has been reported with frequencies of 10%–50%. Children with vitamin B₁₂ deficiency are asymptomatic at birth but may develop severe multisystemic symptoms, including irreversible developmental impairment in the second half-year of life. Early detection of vitamin B₁₂ deficiency allows for presymptomatic treatment. This article provides an overview over the function of vitamin B₁₂ and discusses causes and frequency of vitamin B₁₂ deficiency in newborns, infants, and women of childbearing age. It describes novel successful approaches to newborn screening (NBS) for vitamin B₁₂ deficiency and results of a pilot study which performed systematic NBS for vitamin B₁₂ deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood spots. Recommendations for diagnostics in mothers of children with vitamin B₁₂ deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B₁₂ deficiency detected by NBS. Treatment options of vitamin B₁₂ deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin B₁₂ supplementation. Recommendations for preventive approaches to vitamin B₁₂ deficiency for children and mothers are stated. Many children worldwide could benefit from systematic inclusion of vitamin B₁₂ deficiency into NBS panels. In addition, preventive approaches to maternal vitamin B₁₂ deficiency should be implemented systematically during maternal care.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease that mainly causes dementia. It is a serious threat to the health of the global elderly population. Considerable money and effort has been invested in the development of drug therapy for AD worldwide. Many drug therapies are currently under development or in clinical trials, based on two known mechanisms of AD, namely, Aβ toxicity and the abnormal Tau hyperphosphorylation. Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation, neurotransmitter imbalance, oxidative damage and mitochondrial dysfunction, neuron loss and degeneration. Even so, the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited. However, multi-drug combinations may provide a new avenue for drug therapy for AD. In addition, early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles (EVs) that play a role in the regulation of whole-body metabolism. Exosomes are a subtype of EVs, and accumulating evidence indicates that adipose tissue exosomes (AT Exos) mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms. However, the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated. In this review, we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders. Moreover, we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.

Long COVID symptoms typically occur within 3 months of an initial COVID-19 infection, last for more than 2 months, and cannot be explained by other diagnoses. The most common symptoms include fatigue, dyspnea, coughing, and cognitive impairment. The mechanisms of long COVID are not fully understood, but several hypotheses have been put forth. These include coagulation and fibrosis pathway activation, inflammatory and autoimmune manifestations, persistent virus presence, and Epstein-Barr virus reactivation. Hyperbaric oxygen therapy (HBOT) is a therapeutic method in which a person inhales 100% oxygen under pressure greater than that of the atmosphere. HBOT has some therapeutic effects, including improvement of microcirculation, inhibition of cytokine release leading to a reduction in inflammatory responses, inhibition of autoimmune responses, and promotion of neurological repair. Several clinical trials have been carried out using HBOT to treat long COVID. The results suggest that HBOT helps to improve symptom severity, reduce symptom duration, and enhance patients’ quality of life. It is believed that HBOT is an effective option for patients with long COVID, which is worth actively promoting.

Integrins such as αvβ3, α5β1 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier (BBB) leakage induced by vascular endothelial growth factor (VEGF) and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.

Tumors are believed to consist of a heterogeneous population of tumor cells originating from rare cancer stem cells (CSCs). However, emerging evidence suggests that tumor may also originate from non-CSCs. To support this viewpoint, we are here to present definitive evidence indicating that the number of tumorigenic tumor cells is greater than that of CSCs in tumor, and tumor can also derive from non-CSCs. To achieve this, an idealized mathematical model was employed in the present study and theoretical calculation revealed that non-CSCs could initiate the occurrence of tumor if their proliferation potential was adequate. Further, experimental studies demonstrated that 17.7%, 38.6% and 5.2% of tumor cells in murine B16 solid melanoma, H22 hepatoma and Lewis lung carcinoma, respectively, were potentially tumorigenic. Thus, based on the aforementioned findings, we propose that the scarce CSCs, if exist, are not the sole source of a tumor.