Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective:To investigate the expression of long non-coding RNA MALAT1, interleukin 6(IL-6) and apoptosis induced factor(AIF) in peripheral venous blood of premature infants with bronchopulmonary dysplasia (BPD) and its clinical significance.Methods:Preterm infants admitted to the Department of Neonatology, Shanghai Children′s Hospital from January 2015 to December 2016 were enrolled.The selection criteria included gestational age (GA) ≥28 weeks and ≤32 weeks, and birth weight (BW) < 1 500 g. According to the diagnosis, they were divided into BPD group (20 cases) and control group (20 cases). The clinical data of the two groups of premature infants were collected and analyzed, and the levels of MALAT1, IL-6 and AIF in the blood of 40 premature infants were detected by real-time polymerase chain reaction (RT-PCR). T test was used to compare gestational age, birth weight, MALAT1, IL-6 and AIF between the two groups. Results:(1)There was no significant differences in sex ( χ2=1.76), gestational age ( t= 0.17) and birth weight ( t=1.25) of premature infants in BPD group, compared with the control group (all P >0.05). (2)Compared with the control group, the expression of MALAT1 in the peripheral blood of premature infants in BPD group were significantly increased (0.273 4±0.067 3 vs. 0.375 5±0.081 9, P<0.05). (3)Compared with the control group, the expression of IL-6 in the peripheral blood of premature infants in BPD group were obviously decreased (1.448 8±0.191 8 vs.4.444 6±0.165 7, P<0.05). (4)Compared with the control group, the expression of AIF in the peripheral blood of premature infants in BPD group were remarkably decreased(0.006 8±0.002 0 vs.0.004 5±0.001 9, P<0.05). Conclusions:MALAT1 and IL-6 levels of long non-coding RNA in BPD and non-BPD preterm infants are different, which may be related to the incidence of BPD.IL-6 may be a predictor of BPD, and MALAT1 may protect premature infants with BPD.

Objective:To study the early predictive value of urine neutrophil gelatinase-associated lipoprotein (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in neonates with severe asphyxia.Method:From January 2019 to June 2020, neonates with severe asphyxia admitted to our hospital within 6 hours after birth were enrolled in the study. The dynamic changes of urine NGAL and KIM-1 at admission, 24 h, 48 h and 1 w after birth were examined. Neonates were assigned into AKI group and non-AKI group according to the clinical practice guidelines for AKI issued by KDIGO (Kidney Disease: Improving Global Outcome). The sensitivity and specificity of NGAL and KIM-1 predicting AKI at different time points were evaluated using ROC curve and area under curve (AUC).Result:According to the diagnostic criteria of neonatal AKI, 9 cases were in the AKI group and 42 cases in the non-AKI group, and the incidence of AKI was 17.6%. Urine NGAL was significantly increased in AKI group at admission and 24 h after birth compared with the non-AKI group [(115.6±75.5) ng/ml vs. (49.8±29.0) ng/ml, (90.7±35.6) ng/ml vs. (55.6±30.7) ng/ml] ( P<0.05). No significant differences existed at 48 h and 1 w after birth between the two groups. At 24 h after birth, urine KIM-1 in the AKI group was significantly higher than the non-AKI group [(808.3±555.3) pg/ml vs. (318.4±234.0) pg/ml, P<0.05] and no significant differences existed between the two groups at admission, 48 h and 1 w after birth. The AUC of NGAL predicting AKI at admission, 24 h, 48 h and 1w after birth were 0.804 (95% CI 0.573~1.000), 0.792 (95% CI 0.580~1.000), 0.732 (95% CI 0.517~0.947) and 0.551(95% CI 0.371~0.730), respectively. The AUC of KIM-1 predicted AKI at admission, 24 h, 48 h and 1 w after birth was 0.860 (95% CI 0.676~1.000), 0.824 (95% CI 0.655~0.993), 0.768 (95% CI 0.622~0.914), 0.622 (95% CI 0.392~0.852), respectively. Conclusion:At admission, 24 h and 48 h after birth, urine NGAL and KIM-1, as kidney injury markers, may predict the occurrence of AKI after severe neonatal asphyxia.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.

In prospective cohort study, multi follow up is often necessary for study subjects, and the observed values are correlated with each other, usually resulting in time-dependent confounding. In this case, the data generally do not meet the application conditions of traditional multivariate regression analysis. Sequential conditional mean model (SCMM) is a new approach that can deal with time-dependent confounding. This paper mainly summarizes the basic theory, steps and characteristics of SCMM.

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.

At present, traditional methods on statistics have limitations in controlling time- varying confounding. This paper introduces an analysis method, parametric g-formula, which would adjust time-varying confounding, and also exemplifies the steps of its implementation for purpose to provide a new reference for researchers to deal with long-term observational data.

Mediation analysis is mainly used to explore the causal mechanism between independent variable X and dependent variable Y. It determines whether mediator M plays a role and evaluate the role’s degree in the causal path by decomposing the causal path between the independent variable X and the dependent variable Y. However, the classical mediation analysis is generally used for single mediator. This paper introduces a new mediation analysis method for multiple mediators.

Basal metabolic rate (BMR) is of great significance to the setting of daily energy requirements and the scientific diet guidance for the population. There are 3 kinds of measurement methods for BMR, including the direct calorimetry, the indirect calorimetry, and the equation estimation. The direct calorimetry method is difficult to implement and is only used in some special populations. The indirect calorimetry and the equation estimation are two methods that are currently used commonly. The indirect calorimetry is highly accurate and suitable for individual for basal metabolic measurement or datum collection via equation estimation. The equation estimation is simple and convenient, which is suitable for large samples.
Basal Metabolism ; physiology ; Biomedical Research ; Calorimetry, Indirect ; Energy Metabolism ; Humans

As a metabolic disorder during pregnancy,gestational diabetes mellitus (GDM) has an important effects on fetal development,neonatal health and maternal long-term health,and is one of the pregnancy complications with high incidence.It is of great significance that we have an accurate understanding of the etiology and risk factors of GDM for its prevention and control.GDM is a complex disease with multiple etiologies.Current studies have shown that the occurrence of GDM may be the result of combined effect of heredity and environment,but the exact etiology is still unclear.In this paper,we summarized the possible etiologies and risk factors of GDM,so as to understand the occurrence and development of GDM better and to provide possible references for prevention and further etiological studies of GDM.