Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Effects of the linoleic acid/docosahexaenoic acid ratio and concentration inducing autophagy in Raw264.7 cells against Staphylococcus aureus.

Our study was to understand the autophagy induce by different ratios and concentrations of LA/DHA on Raw264.7 cell, and then to investigate the effect of Raw264.7 autophagy on the clearance of Staphylococcus aureus. Raw264.7 cells was treated by LA/DHA in different concentrations (50/100 µmol/L) and ratios (4:1, 6:1, 8:1, 1:4, 1:6 and 1:8) for 6/12/24 h, cell viability assay was assessed by Cell Counting Kit-8, LC3B, p62, P-mTOR, P-Akt, P-PI3K and BECN 1 were detected by the Western blot. LA/DHA could induce autophagy of Raw264.7 cells through the PI3K-Akt-mTOR signaling pathway, the strong effect on autophagy by the concentration is 100 µmol/L, the ratio is 6:1 of LA/DHA, and the treatment time is 24 h. Compared with the images in the control group obtained by merging red and green fluorescence channels, the treatment of LA, DHA in a ratio of 6:1 at a concentration of 100 µmol/L for 24 h significantly lead to a substantial number of autophagosomes (yellow) as well as autolysosomes (red), enhancing autophagy flux. Autophagy induce by LA/DHA can devour and damage intracellular and extracellular Staphylococcus aureus. These results indicate that LA/DHA cloud induce autophagy and enhance the phagocytosis and killing ability of macrophages to intracellular parasitic bacteria.

LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have drawn increasing attention because they play a pivotal role in various types of autoimmune diseases, including rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion which can lead to joint destruction. In this study, we investigated whether lncRNAs could act as competing endogenous RNAs to regulate the pathological behaviors of RA-FLSs. METHODS: LncRNA microarray was conducted to establish lncRNA expression profiles in FLSs isolated from RA patients and healthy controls (HCs). Differentially expressed lncRNAs were verified by quantitative real-time PCR (qRT-PCR) on RA-FLSs and synovial fluid. The functional role of lncRNA PICSAR downregulation was evaluated in RA-FLSs. We conducted molecular biological analysis to predict miRNAs which have a potential binding site for PICSAR and further refined the results by qRT-PCR. Luciferase reporter assay was adopted to validate the interaction of lncRNA PICSAR and miR-4701-5p. Western Blot and qPCR were used to identify the target gene and protein. The functional role of miR-4701-5p upregulation was examined in RA-FLSs. FINDINGS: We identified a long intergenic non-protein-coding RNA162 (LINC00162), also known as lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), has significantly higher expression in RA-FLSs and RA synovial fluid. The cell proliferation, migration, invasion and proinflammatory cytokines production of RA-FLSs showed significant alterations after the lncRNA PICSAR suppression. Mechanistically, lncRNA PICSAR functioned through sponging miR-4701-5p in RA-FLSs. INTERPRETATION: Our results reveal PICSAR may exert an essential role in promoting synovial invasion and joint destruction by sponging miR-4701-5p in RA and that lncRNA PICSAR may act as a biomarker of RA.

Novel non-synonymous mutations of PAX8 in a cohort of Chinese with congenital hypothyroidism.

BACKGROUND: The transcription factor paired box 8 (PAX8) was associated with type 2 congenital non-goitrous hypothyroidism (CHNG2), a clinical phenotype of congenital hypothyroidism (CH). Though studied in a few regions with different ethnicities, the incidence of PAX8 mutations varied, even among Chinese cohorts in different regions. This study aimed to identify and characterize PAX8 mutations and explore the prevalence of its mutations in another cohort of CH. METHODS: The 105 unrelated Chinese patients with CH were collected from four major hospitals. Exomes of the 105 samples were sequenced by Hiseq 2000 platform to identify mutations of PAX8 on genomic DNAs extracted from peripheral blood samples. Luciferase reporter assays were used to assess the effects of mutations on the transcription of thyroid peroxidase (TPO). RESULTS: Three PAX8 mutations in four subjects were identified in 105 samples. One variant, rs189229644, was detected in two subjects, and categorized as uncertain significance. The other two missense mutations (275T>C/Ile92Thr and 398G>A/Arg133Gln) were not detected in three large-scale genotyping projects, namely 1000 Genome Project, Exome Aggregation Consortium and GO Exome Sequencing Project. Functional studies for the two mutations revealed that they could impair the transcription ability of PAX8 on one of its target genes, TPO. Therefore, the two mutations were causative for the pathogenesis of CHNG2. After combining the studies of PAX8 mutations, an average frequency of 1.74% (21/1209) could be obtained in Chinese patients with CH. CONCLUSION: The study specifically demonstrates the role of two mutations in impairing the transcription ability of PAX8, which should be considered as pathogenic variants for CH.

Effect of Cesarean Section on the Severity of Postpartum Hemorrhage in Chinese Women: The Shanxi Study.

Postpartum hemorrhage (PPH) is one of the most adverse obstetric outcomes. Our aim is to detect the risks of multilevel PPH in different cesarean section (CS) groups [including nulliparous CS with indications, nulliparous CS without indications, repeat cesarean (RC), vaginal birth after cesarean (VBAC), cesarean after vaginal birth (CAVB)]. We conducted a retrospective cohort study, and the data on 127 145 women collected from January 2014 to May 2016 and from 35 tertiary hospitals in Shanxi province, China, were reviewed. Based on the measuring results of PPH, an ordered logistic regression model was used to analyze the adjusted PPH risks for each of the CS groups, and comparisons were drawn between them. Finally, a total of 99 066 nulliparous (77.92%) and 28 079 multiparous (22.08%) women were observed. The number of CS cases was 61 117, and the rate for CS was 48.07%. A total of 10 029 women did not show indications for CS and accounted for 16.41% of the CS parturient, whereas 9103 women underwent a repeated cesarean, with a CS frequency of 14.89%. The number of VBAC cases was 989, whose rate was 9.88% in prior CS women. The number (proportions) of PPH was 3658 (2.88%) in LI (PPH volume: ≥900 and <1500 mL), 520 (0.41%) in 12 (PPH volume: >1500 and <2100 mL), and 201 (0.16%) in L3 (PPH volume: ≥2100 mL). The Ln (n=l, 2,3, etc.) represented the increasing order of PPH severity. In the adjusted results, compared with spontaneous vaginal delivery (SVD) as the reference group, in the adjusted result for nulliparous, there was a decreased PPH risk in CS with indications (OR: 2.32; CI: 2.04-2.62), which was lower than that of CS without indications (OR: 2.50; CI: 2.01-2.96). The highest PPH risk in all subgroups (i.e. nulliparous and multiparous groups) was observed in the RC (OR: 3.61; CI: 3.16-4.17), which was nearly twice higher than that of the VBAC (OR: 1.82; CI: 1.33-2.52). CAVB (OR: 1.03; CI: 0.65-1.62) showed no significant difference with the reference group. Thus, we deemed that CS should be avoided in nulliparous pregnancies unless indicated, to prevent or reduce the rates for the use of RC or VBAC which are high risks of severe PPH to the parturient women.

[Screening Method of Priority Control Pollutants in Groundwater Based on Contamination Assessment].

Screening of priority control pollutants is an effective technical means for environmental management and environmental quality protection. Quick and efficient identification of pollutants is useful when attempting to prevent and control groundwater pollution. In order to explore a screening system for a set of priority pollutants that can be applied to regions with weak basic information, a screening method of priority pollutants based on contamination assessment is put forward in this paper. Based on the data of groundwater detection and analysis, using the evaluation method for pollution index classification, and combined with the pollution degree frequency score superposition method. The screening method of priority control pollutants in groundwater based on contamination assessment was established. This method was applied to the screening of pollutants in groundwater in the city of Golmud in Qinghai Province, China. The results were verified by using the screening system based on risk assessment, and the differences in the two systems are discussed. The results show that three categories of 10 kinds of chemical parameters, including TDS, total hardness, chloride, sulfate, sodium, fluorine, total iron, pyrene, phenanthrene, and aluminum, were determined as priority control pollutants in the Golmud region. It was consistent with the results of the screening method based on the risk assessment, and the screening results were reliable. The method based on risk assessment is complex and requires additional basic information, but it has certain foresight and is suitable for regions with abundant basic data. The method based on contamination assessment is simple and convenient and requires less abundant basic data. However, it is easily affected by background values. It is more suitable for the screening of priority control pollutants in regions with weak pollution source information.

Identifying and assessing human activity impacts on groundwater quality through hydrogeochemical anomalies and NO3-, NH4+, and COD contamination: a case study of the Liujiang River Basin, Hebei Province, P.R. China.

In the face of rapid economic development and increasing human activity, the deterioration of groundwater quality has seriously affected the safety of the groundwater supply in eastern China. Identifying and assessing the impact of human activities is key to finding solutions to this problem. This study is an effort to scientifically and systematically identify and assess the influence of human activities on groundwater based on irregularities in hydrochemical properties and water contamination, which are considered to directly result from anthropogenic activity. The combination of the hydrochemical anomaly identification (HAI) and the contaminant identification (CI) was proposed to identify the influence of human activities on groundwater quality. And the degree of abnormality was quantified by the background threshold value. The principal component analysis (PCA) and land use map were used to verify the reliability of the identification result. The final result show that the strong influence areas mainly distributed in the south of the basin and the affected indicators contained the major elements and NO3-, NH4+, COD. Impacts from anthropogenic activities can be divided into two types: mine drainage that disrupts natural water-rock interaction processes, agricultural cultivation, and sewage emissions that contribute to nitrate pollution.

Bootstrapping data envelopment analysis of efficiency and productivity of county public hospitals in Eastern, Central, and Western China after the public hospital reform.

China implemented the public hospital reform in 2012. This study utilized bootstrapping data envelopment analysis (DEA) to evaluate the technical efficiency (TE) and productivity of county public hospitals in Eastern, Central, and Western China after the 2012 public hospital reform. Data from 127 county public hospitals (39, 45, and 43 in Eastern, Central, and Western China, respectively) were collected during 2012-2015. Changes of TE and productivity over time were estimated by bootstrapping DEA and bootstrapping Malmquist. The disparities in TE and productivity among public hospitals in the three regions of China were compared by Kruskal-Wallis H test and Mann-Whitney U test. The average bias-corrected TE values for the four-year period were 0.6442, 0.5785, 0.6099, and 0.6094 in Eastern, Central, and Western China, and the entire country respectively, with average non-technical efficiency, low pure technical efficiency (PTE), and high scale efficiency found. Productivity increased by 8.12%, 0.25%, 12.11%, and 11.58% in China and its three regions during 2012-2015, and such increase in productivity resulted from progressive technological changes by 16.42%, 6.32%, 21.08%, and 21.42%, respectively. The TE and PTE of the county hospitals significantly differed among the three regions of China. Eastern and Western China showed significantly higher TE and PTE than Central China. More than 60% of county public hospitals in China and its three areas operated at decreasing return scales. There was a considerable space for TE improvement in county hospitals in China and its three regions. During 2012-2015, the hospitals experienced progressive productivity; however, the PTE changed adversely. Moreover, Central China continuously achieved a significantly lower efficiency score than Eastern and Western China. Decision makers and administrators in China should identify the causes of the observed inefficiencies and take appropriate measures to increase the efficiency of county public hospitals in the three areas of China, especially in Central China.

[Comparison and Analysis of the Quantitative Methods for Pollutant Sources Load in Groundwater Contamination Risk Assessment].

Groundwater contamination risk assessment is an important basis for the protection of groundwater resources and the prevention and control of groundwater pollution. Its evaluation system is usually composed of three elements, which is vulnerability, pollutant source load and groundwater value. The pollutant source load plays an important role in risk assessment. Because of the difference among methods for pollutant sources load quantification, there will inevitably be different demand for the basic information survey on pollutant sources, as well as unknown impact on the final assessment results. In order to explore the impact of quantitative methods for pollutant sources load on groundwater contamination risk assessment, a case study was conducted in the mesoscale region of alluvial fan in Hutuo River, China. The two representative methods of grading index and quantitative index assessment systems were applied to quantify the pollutant sources load, in combination with the same vulnerability and groundwater value. The results constructed from different risk assessment systems were compared. The results showed that there were great differences between the two methods of quantification for pollutant sources load, and the result of contamination risk assessment also revealed significant differences in the feature of risk valve and the spatial distribution of the risk levels. The results of contamination risk assessment were strongly influenced by the choice of quantification for pollutant sources load methods. The grading index method was suitable for large scale region with lower precision of basic information and was simple, and the results of assessment had relatively lower reliability. The quantitative index method was suitable for the mesoscale and micro-scale region with higher precision of basic information and was relatively complicated, and the results of assessment had relatively higher reliability. It was shown that the scale effect of evaluation region had an important influence on the choice of methods.

Analysis of high alert medication knowledge of medical staff in Tianjin: A convenient sampling survey in China.

The current situation of medical staff's awareness about high alert medication was investigated in order to promote safe medication and standardized management of the high alert medication in China. Twenty questions were designed concerning elementary knowledge of high alert medications, storage management, medication issues and risks. In order to understand the knowledge level and education status of high alert medication, a convenient survey was conducted among 300 medical staffs in Tianjin. Medical staff's average score of high alert medication knowledge was 12.43±0.27, and the average scores of elementary knowledge of high alert medication, storage management, medication issues and risks were 3.38±0.11, 2.46±0.14, 3.17±0.11 and 3.41±0.12 respectively. Occupation (F=4.86, P=0.003), education background (F=5.57, P=0.019) and professional titles (F=13.44, P≤0.001) contributed to the high alert medications knowledge scores. Currently, the most important channel to obtain high alert medication knowledge was hospital files or administrative rules, and clinical pharmacist seminars were the most popular education form. It was suggested that the high alert medication knowledge level of the medical staff needs to increase, and it might benefit from targeted, systematic and diverse training to the medical staff working in the different circulation nodes of the medications. Further research to develop and validate the instrument is needed.

[The fluorescence of terbium complex and its application in wavelength conversion membrane].

Terbium was selected as test material for its strong fluorescence effect, and sulfosalicylic acid was used as first ligand, polyvinyl alcohol and polyethylene glycol 2000 as co-ligand, the fluorescence property of complexes in the two systems of ethanol solution and aqueous solution was explored. It was obtained that the polyvinyl alcohol and polyethylene glycol 2000 are the excellent co-ligands. Further study showed that sufactant is good for fluorescence enhancement of the different complexes and especially sodium dodecyl sulfate is best while exploring the impact of acidity on the fluorescence intensity. Terbium-sulfosalicylic acid-polyvinyl alcohol complex was obtained under the conditions of 342 nm for excitation wavelength, and 545 nm for emission wavelength. Mixing the complex into the plastic film in proper proportion, the authors prepared the rare earth light conversion membrane which allowed ultraviolet portion of sunlight to convert to green light the crop photosythesis needed to effectively improve the photosynthetic efficiency.

Production of CCHF virus-like particle by a baculovirus-insect cell expression system.

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a tick-born virus of the Nairovirus genus within the Bunyaviridae family, which is widespread and causes high fatality. The nucleocapsid of CCHFV is comprised of N proteins that are encoded by the S segment. In this research, the N protein of CCHFV was expressed in insect cells using a recombinant baculovirus. Under an electron microscope, Virus-Like Particles (VLPs) with various size and morphology were observed in cytoplasmic vesicles in the infected cells. Sucrose-gradient purification of the cell lysate indicated that the VLPs were mainly located in the upper fraction after ultracentrifugation, which was confirmed by Western blot analysis and immuno-electron microscopy (IEM).