Characteristics of lymphocyte subsets and cytokine profiles of patients with COVID-19.

BACKGROUND: Abnormalities of lymphocyte subsets and cytokine profiles have been observed in most patients with coronavirus disease (COVID-19). Here, we explore the role of lymphocyte subsets and cytokines on hospital admission in predicting the severity of COVID-19. METHODS: This study included 214 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 19, 2020 to April 30, 2020. Any mutants were not detected in the studied patients. Patients were divided into non-intensive care unit (ICU) (mild/moderate) group and ICU (severe/critical) group, according to the severity of the disease. Clinical and laboratory data, including peripheral lymphocyte subsets and cytokines, were analyzed and compared. Logistic regression was used to analyze the predictive factors for ICU admission. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of selected indicators for the severity of COVID-19. RESULTS: Of the 214 patients enrolled, 161 were non-ICU patients and 53 were ICU patients. Lymphopenia was observed in nearly all of ICU patients (96.2%) and 84.5% of non-ICU patients on hospital admission. The absolute number of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and natural killer (NK) cells were lower in ICU group (659.00 × 106/L, 417.00 × 106/L, 261.00 × 106/L, 140.00 × 106/L, 109.00 × 106/L, 102.00 × 106/L, respectively) than in non-ICU group (1063.00 × 109/L, 717.00 × 106/L, 432.00 × 106/L, 271.00 × 106/L, 133.00 × 106/L, 143.00 × 106/L, respectively). Interleukin (IL)-6 was significantly higher in ICU patients than in non-ICU patients (18.08 pg/mL vs. 3.13 pg/mL, P < 0.001). Multivariate logistic regression analysis showed that age (odds ratio: 1.067 [1.034-1.101]), diabetes mellitus (odds ratio: 9.154 [2.710-30.926]), CD3+ T cells (odds ratio: 0.996 [0.994-0.997]), and IL-6 (odds ratio: 1.006 [1.000-1.013]) were independent predictors for the development of severe disease. ROC curve analysis showed that the area under the ROC curve (AUC) of CD3+ T cells and IL-6 was 0.806 (0.737-0.874) and 0.785 (0.705-0.864), respectively, and the cutoff values were 510.50 × 106/L (sensitivity, 71.7%; specificity, 79.5%) and 6.58 pg/mL (77.4%, 74.5%), respectively. There were no statistical differences among all tested indicators of lymphocyte subsets and cytokines between severe group (n = 38) and critical group (n = 15) on hospital admission or ICU admission, respectively. CONCLUSIONS: The levels of lymphocyte subsets decreased and the level of IL-6 increased significantly in ICU COVID-19 patients compared with non-ICU COVID-19 patients. Therefore, the number of CD3+ T cells and the level of IL-6 on hospital admission may serve as predictive factors for identifying patients with wild-type virus infection who will have severe disease.

Promoter methylation changes in the placenta involved in the relationship between prenatal depression and small for gestational age.

BACKGROUND: Recent studies suggest that the incidence of small for gestational age (SGA) birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the changes of promoter methylation in the placenta which may be involved in the relationship between prenatal depression and SGA. METHODS: Three hundred forty-five pregnant women were enrolled in this prospective cohort study. Perinatal emotion and sleep quality in the second and third trimesters were assessed using self-rating depression scale, self-rating anxiety scale, and Pittsburgh sleep quality index. According to the exposure (depressed emotion of mother) and outcome (SGA), the placentas were divided into four groups. Methylation of the promoter regions of the placental CRH, HSD11ß2, SLA16A10, DIO3, and MTNR1B genes was determined using next generation sequencing based on bisulfite sequencing PCR. RESULTS: There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. Thirty-five pregnant women had an SGA birth. The incidence of SGA births in this prospective cohort was 10.1%. The risk factors of SGA birth were low BMI of pregnancy women (RR = 0.71, 95%CI = 0.54 ~ 0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18 ~ 18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31 ~ 12.16). We found that the CRH and HSD11ß2 methylation levels were higher in the depression group than those in the non-depression group. Methylation levels of DIO3 were higher in SGA group than that in the non-SGA group. Higher methylation levels of CRH correlated with higher methylation levels of DIO3 in the placenta. CONCLUSIONS: Maternal depression in the second trimester may lead to the changes of methylation levels in the promoter region of CRH and HSD11ß2 gene, while the changes of methylation of DIO3 in subsequent could related to SGA. This study suggests that maternal depressed emotion during pregnancy may result in SGA due to the epigenetic changes of placenta.

Nanozyme Based on Dispersion of Hemin by Graphene Quantum Dots for Colorimetric Detection of Glutathione.

Compared with natural enzymes, nanozymes have the advantages of good catalytic performance, high stability, low cost, and can be used under extreme conditions. Preparation of highly active nanozymes through simple methods and their application in bioanalysis is highly desirable. In this work, a nanozyme based on dispersion of hemin by graphene quantum dot (GQD) is demonstrated, which enables colorimetric detection of glutathione (GSH). GQD was prepared by a one-step hydrothermal synthesis method. Hemin, the catalytic center of heme protein but with low solubility and easy aggregation that limits its catalytic activity, can be dispersed with GQD by simple sonication. The as-prepared Hemin/GQD nanocomplex had excellent peroxidase-like activity and can be applied as a nanozyme. In comparison with natural horseradish peroxidase (HRP), Hemin/GQD nanozyme exhibited a clearly reduced Michaelis-Menten constant (Km) when tetramethylbenzidine (TMB) was used as the substrate. With H2O2 being the substrate, Hemin/GQD nanozyme exhibited a higher maximum reaction rate (Vmax) than HRP. The mechanisms underlying the nanozyme activity were investigated through a free radical trapping experiment. A colorimetric platform capable of sensitive detection of GSH was developed as the proof-of-concept demonstration. The linear detection range was from 1 µM to 50 µM with a low limit of detection of 200 nM (S/N = 3). Determination of GSH in serum samples was also achieved.

Analysis of the coupling degree between regional logistics efficiency and economic development coordination.

This paper aims to study the relationship between regional logistics efficiency and economic development in 31 provinces of China and analyze their coupling coordination. To comprehensively evaluate the coordination between logistics and the economy, we introduced external indicators, such as carbon emissions, based on traditional evaluation indicators. We constructed an evaluation index system to coordinate regional logistics efficiency and economic development. The research approach used in this paper is the cross-DEA method, and data from 2010 to 2019 were selected for empirical calculation. The research findings indicate that Eastern and Northern regions of China show higher logistics efficiency, while Northwestern and Southwestern regions exhibit lower logistics efficiency. Coastal areas have relatively higher economic development levels compared to inland areas. Regarding the coupling coordination between logistics efficiency and economic development, different regions show temporal fluctuations and spatial disparities. Some regions demonstrate higher coordination between logistics efficiency and economic development, while others show lower coordination. Additionally, as the economy experiences rapid growth, logistics efficiency also improves, but the level of coordination varies among different provinces.

Equipment of Vertically-Ordered Mesoporous Silica Film on Electrochemically Pretreated Three-Dimensional Graphene Electrodes for Sensitive Detection of Methidazine in Urine.

Direct, rapid, and sensitive detection of drugs in complex biological samples is essential for drug abuse control and health risk assessment. In this work, an electrochemical sensor was fabricated based on equipment of vertically-ordered mesoporous silica film (VMSF) on an electrochemically pre-treated three-dimensional graphene electrode (p-3DG), which can achieve direct and sensitive determination of methylthiopyridazine (TR) in urine. Three-dimensional graphene (3DG) with a continuous and interpenetrating graphene network was used as the supporting electrode and simple electrochemical polarization was employed to pre-treat 3DG to improve surface hydrophilicity and electrocatalytic performance. VMSF was easily grown using an electrochemical assisted self-assembly method within 10 s and was stably bound to the p-3DG surface. The nanochannel array on the as-prepared VMSF/p-3DG sensor enriched positively charged TR, leading to significantly improved electrochemical signal. Combined with the high electric activity of p-3DG and the enrichment of nanochannels, VMSF/p-3DG realized sensitive determination of TR ranging from 50 nM to 10 µM with a low detection limit (DL, 30 nM). Owing to the anti-fouling and anti-interference performance of VMSF, the common electroactive molecules including ascorbic acid (AA) and uric acid (UA) did not interfere with the detection. In addition, the detection of TR in buffer and urine exhibited similar sensitivity. Accurate detection of TR in urine was realized.

Colorimetric and Fluorescent Dual-Modality Sensing Platform Based on Fluorescent Nanozyme.

Compared with natural enzymes, nanozymes based on carbonaceous nanomaterials are advantages due to high stability, good biocompatibility, and the possibility of multifunctionalities through materials engineering at an atomic level. Herein, we present a sensing platform using a nitrogen-doped graphene quantum dot (NGQD) as a highly efficient fluorescent peroxidase mimic, which enables a colorimetric/fluorescent dual-modality platform for detection of hydrogen peroxide (H2O2) and biomolecules (ascorbic acid-AA, acid phosphatase-ACP) with high sensitivity. NGQD is synthesized using a simple hydrothermal process, which has advantages of high production yield and potential for large-scale preparation. NGQD with uniform size (3.0 ± 0.6 nm) and a single-layer graphene structure exhibits bright and stable fluorescence. N-doping and ultrasmall size endow NGQD with high peroxidase-mimicking activity with an obviously reduced Michaelis-Menten constant (K m) in comparison with natural horseradish peroxidase. Taking advantages of both high nanozyme activity and unique fluorescence property of NGQD, a colorimetric and fluorescent dual-modality platform capable of detecting H2O2 and biomolecules (AA, ACP) with high sensitivity is developed as the proof-of-concept demonstration. Furthermore, the mechanisms underlying the nanozyme activity and biosensing are investigated.

The effect of pestle acupuncture for patients with lactation insufficiency after cesarean section: Study protocol for a randomized controlled trial.

INTRODUCTION: Cesarean section is a common operation in obstetrics, and the incidence of insufficient breast milk is high in parturients undergoing cesarean section. Studies have shown that acupuncture or massage at related acupoints can promote the secretion and excretion of milk. These external treatments are quick, safe, and effective. On the other hand, they can avoid the potential risk of changes in milk composition that may be caused by the use of drugs. Pestle needle therapy is a new branch of traditional acupuncture, and pestle needle operation does not need to break the skin. The pestle needle has good clinical efficacy and safety in cervical spondylosis, insomnia, fatigue, depression, and so on, but few studies have focused on the effect of pestle acupuncture for patients with lactation insufficiency after cesarean section. This study aims to determine whether pestle needle therapy is effective and safe in the treatment of postpartum milk deficiency. METHODS: This is a 2 parallel-group, assessor-blinded, randomized controlled trial.128 patients with lactation insufficient after cesarean section will be recruited and randomly divided into control group and the pestle needle group in a 1:1 ratio. The control group will receive routine nursing care of milk deficiency. In the pestle needle group, pestle needles will be used to operate on the acupoints such as bilateral Shao ze (S11), bilateral Ru gen (ST18), Dan zhong (DU14), 8 array acupoints of Shen dao (DU11) and so on. It will be operated once a day for 5 days. The primary outcomes are milk yield, degree of breastfilling, degree of milk siltation and other milk deficiency symptom, and serum prolactin. Secondary outcomes include syndrome of traditional Chinese medicine, such as facial expression, fatigue, loss of appetite, and so on. DISCUSSION: Pestle needle therapy based on acupoint and meridian theory may increase milk secretion and excretion, which will provide a new intervention means to promote breastfeeding and have great significance to guide clinical treatment. TRIAL REGISTRATION NUMBER: ChiCTR2000039752.