ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease.

Impact of group cognitive behavioral therapy counseling on cognitive control among college students with high obsessive compulsive traits / 中国学校卫生

Objective@#To explore the effect of group cognitive behavioral therapy (GCBT) on cognitive control among college students with high obsessive compulsive traits, to provide basic information for the psychological counseling intervention for college students.@*Methods@#From March to April 2019, 687 students were conveniently selected from 2 universities in Hefei. According to the inclusion and exclusion criteria, 58 students with high obsessive traits were selected and divided into experimental group ( n =29) and control group ( n =29) by random number table method. The experimental group received cognitive behavioral group counseling for 4 weeks (1.5 h each time, twice a week), while the control group receive no intervention. The Obsessive Compulsive Inventory Revised (OCI-R), Stroop Color Word Test (SCWT), Digital Span Test (DST), and Wisconsin Card Sorting Test (WSCT) were used to assess in two groups at baseline and 4 weeks later.@*Results@#After 4 weeks, the scores of OCI-R in the GCBT group (10.28±7.22) was lower than that of in the control group (15.90±10.20) ( t=2.42, P<0.05). Before and after intervention, compared with the control group [(21.89±6.63, 20.52±7.37)s, (8.62±4.43, 8.04±4.84)s] in Stroop C and Stroop interfere effects (SIE), the GCBT group [(22.14±4.92, 16.81±3.43)s, (8.36±3.87, 4.82±1.86)s], the interaction of time group was statistically significant ( F =14.60, 10.54, P <0.05). Compared with the control group (6.21±1.35, 6.55±1.45)times, the scores of DST reverse in the GCBT group (6.31±1.44, 7.24±1.38) times were statistically significant ( F=3.96, P <0.05).@*Conclusion@#It suggests that cognitive behavioral group counseling can improve the inhibitory control and working memory of college students with high obsessive compulsive traits, but does not change the cognitive flexibility.

Effect of stearic or oleic acid on milk performance and energy partitioning when fed in diets with low and high rumen-active unsaturated fatty acids in early lactation.

This experiment was conducted to determine the effects of stearic acid (SA; C18:0) or rumen-protected oleic acid (OA; C18:1 cis-9) on milk performance and energy partitioning of early lactation cows when supplemented in diets with low and high level of rumen unsaturated fatty acids (RUFA). In low RUFA experiment (LRUFA), FA supplement rich in either SA or calcium salts OA was added to a basal diet with a low concentration of RUFA (0.75% vs. 1.4%, LRUFA-SA vs. LRUFA-OA). In high RUFA experiment (HRUFA), 2% soybean oil was added to the diet fed in the LRUFA experiment. In each experiment, 30 multiparous cows were blocked by parity and predicted transmitting ability for milk yield and were randomly fed 1 of 2 treatment diets from 2 to 13 wk postpartum. In the LRUFA experiment, LRUFA-SA had 2.4 kg/d more dry matter intake (DMI) (P < 0.01), 3.8 kg/d more energy-corrected milk (P < 0.01), and 0.3% units more milk fat percentage (P < 0.01) and 0.2 kg/d more milk fat yield (P < 0.01). Dietary treatments did not affect body weight, energy balance, and energy intake partitioning into milk, maintenance, and body tissues (P > 0.1). In the HRUFA experiment, HRUFA-SA had 1.4 kg/d more DMI (P = 0.03) but similar milk and milk components yields (P > 0.1). HRUFA-SA had a tendency to gain more body weight (P = 0.07) and had more positive energy balance (P = 0.01) and decreased gross feed efficiency (milk yield/DMI) (P = 0.01). Consistently, HRUFA-SA increased intake energy partitioning into body tissues (P = 0.02) and decreased energy partitioning into milk (P = 0.01). In summary, SA supplementation had more DMI relative to OA, but the effects on milk and milk fat production were different and affected by the level of RUFA in the basal diet. In application, SA supplementation was more effective to improve milk production when included in the basal diet with the low RUFA.

Rehabilitation nursing of a patient with pleural giant solitary fibroma with Doege-Potter syndrome / 中国实用护理杂志

Objective@#To summarize the clinical rehabilitation nursing practice of a patient with pleural giant solitary fibroma with Dege-Port syndrome.@*Methods@#A preoperative and postoperative rehabilitation nursing of a patient with low pulmonary function pleural giant solitary fibroma and non-islet cell hypoglycemia was analyzed and summarized.@*Results@#After psychological, hypoglycemia, and pulmonary rehabilitation, the patient was tolerant to surgery and recovered well after surgery. He was discharged from hospital on the 13th day after surgery.@*Conclusions@#For patients with difficult diagnosis, long-term pleural giant solitary fibroma with hypoglycemia and low lung function, psychological nursing, hypoglycemia symptomatic treatment, pulmonary rehabilitation to improve lung function, close observation and prevention of serious complications in patients It plays a vital role in the course of the disease and rehabilitation.

Rehabilitation nursing of a patient with pleural giant solitary fibroma with Doege-Potter syndrome / 中国实用护理杂志

Objective To summarize the clinical rehabilitation nursing practice of a patient with pleural giant solitary fibroma with Dege-Port syndrome. Methods A preoperative and postoperative rehabilitation nursing of a patient with low pulmonary function pleural giant solitary fibroma and non-islet cell hypoglycemia was analyzed and summarized. Results After psychological, hypoglycemia, and pulmonary rehabilitation, the patient was tolerant to surgery and recovered well after surgery. He was discharged from hospital on the 13th day after surgery. Conclusions For patients with difficult diagnosis, long-term pleural giant solitary fibroma with hypoglycemia and low lung function, psychological nursing, hypoglycemia symptomatic treatment, pulmonary rehabilitation to improve lung function, close observation and prevention of serious complications in patients It plays a vital role in the course of the disease and rehabilitation.

Dose- and type-dependent effects of long-chain fatty acids on adipogenesis and lipogenesis of bovine adipocytes.

Differentiation and lipid metabolism of adipocytes have a great influence on milk performance, health, and feed efficiency of dairy cows. The effects of dietary long-chain fatty acids (FA) on adipogenesis and lipogenesis of dairy cows are often confounded by other nutritional and physiological factors in vivo. Therefore, this study used an in vitro approach to study the effect of dose and type of long-chain FA on adipogenesis and lipogenesis of bovine adipocytes. Stromal vascular cells were isolated from adipose tissue of dairy cows and induced into mature adipocytes in the presence of various long-chain FA including myristic, palmitic, stearic, oleic, or linoleic acid. When concentrations of myristic, palmitic, and oleic acids in adipogenic mediums were 150 and 200 µM, the induced mature adipocytes had greater lipid content compared with other concentrations of FA. In addition, mature adipocytes induced at 100 µM stearic acid and 300 µM linoleic acid had the greatest content of lipid than at other concentrations. High concentrations of saturated FA were more toxic for cells than the same concentration of unsaturated FA during the induction. When commitment stage was solely treated with FA, the number of differentiated mature adipocytes was greater for oleic and linoleic acids than other FA. When the maturation stage was treated with FA, the number of mature adipocytes was not affected, but the lipid content in adipocytes was affected and ranked oleic > linoleic > myristic > stearic > palmitic. In summary, this study showed that adipogenesis and lipogenesis of bovine adipocytes were differentially affected by long-chain FA, with unsaturated FA more effective than saturated FA.

Quercetin attenuates Ox-LDL-induced calcification in vascular smooth muscle cells by regulating ROS-TLR4 signaling pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine whether quercetin inhibits oxidized low-density lipoprotein (Ox-LDL)-induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) and understand the underlying mechanism.</p><p><b>METHODS</b>The calcification of human VSMCs following Ox-LDL treatment was assessed using alizarin red staining and by detecting ALP activity. The mRNA expressions of the bone-related genes including Msx2, BMP2 and Osterix, and the contractile proteins including SMA and SM22a were analyzed using qPCR. The effects of quercetin were investigated on OxLDL-induced VSMC calcification and changes in ALP activity, expressions of Msx2, BMP2, Osterix, SMA and SM22a, ROS levels and SOD activity. The effect of Toll like receptor 4 (TLR4) silencing mediated by siRNA transfection on cell calcification, ALP activity, gene expressions and ROS levels were investigated.</p><p><b>RESULTS</b>Ox-LDL treatment promoted VSMC calcification and up-regulated TLR4 expression. Quercetin treatment significantly attenuated Ox-LDL-induced VSMC calcification, reduced ALP activity, down-regulated the expression levels of Msx2, BMP2 and Osterix, and up-regulated the expressions of vascular smooth muscle contractile proteins SMA and SM22a. In addition, Quercetin treatment markedly increased SOD activity, reduced ROS levels and TLR4 expression in VSMCs. Silencing TLR4 expression using TLR4 siRNA also significantly decreased calcification of the VSMCs.</p><p><b>CONCLUSIONS</b>Quercetin inhibits Ox-LDL-induced VSMC calcification in VSMCs possibly by targeting the ROS/TLR4 signaling pathway.</p>

Quality appraisal of evidence-based guidelines on prevention and repair of perineal injury at vaginal delivery / 中华护理杂志

Objective To review the methodological quality of evidence-based guidelines on prevention and repair of perineal injury at vaginal delivery,and analyze the characteristics of guidelines to provide references for evidence-based decision-making.Methods We systematically searched websites of professional organizations,websites of clinical practice guidelines and databases for guidelines on prevention and repair of perineal injury,and used AGREE Ⅱ to evaluate the chosen guidelines.Results We identified totally 7 relevant evidence-based guidelines in this field.The average standardized scores of guidelines in 6 domains of AGREE Ⅱ were 90.21％(scope and purpose),68.25％ (stakeholder involvement),69.94％ (rigor of development),89.41％ (clarity of presentations),70.63％ (applicability),and 68.25％(independence),respectively.The overall standardized score for 7 guidelines was 75.65％,and the total score was 5.67 (7 points).For overall quality,4 of them were grade A and 3 of them were grade B.Conclusion The overall quality of included guidelines were high,but stakeholder involvement,rigor of development and independence in some guidelines needs to be improved.There was no Chinese evidence-based gui-deline in this field,and high-quality foreign guidelines could be used as evidence in combination with local conditions.

Effect of Jinghou Zengzhi Recipe on Fas pathway in ovarian granulosa cells of controlled ovarian hyper-stimulation rats / 实用医学杂志

Objective To investigate the effect of Jinghou Zengzhi Recipe(JHZZR)on Fas apoptosis pathway in ovarian granulosa cells of rats with controlled ovarian hyperstimulation(COH)and to investigate the possible mechanism of the effect of JHZZR on improving oocyte quality. Methods To establish the model of COH,30 rats were randomly divided into the blank group,the positive group and the TCM group.The expression of Fas,Fasl,Caspase8,Caspase3 in ovarian was detected by qPCR andWestern Blot assay,respectively. Results The expression of Fas,Fasl,Caspase8,Caspase3 was lowered in the blank group and the TCM group. Conclusion JHZZR can inhibit Fas signalling,suggesting that Fas pathway may be one of the mechanisms under-lying that JHZZR improves oocyte quality.

Iodine excess and its effects on human health / 中华地方病学杂志

Iodine is an essential trace element,its physiological function is realized through thyroid hormone,both iodine deficiency and excess have influences on human health.After 20-year implementation of universal salt iodization in China,the iodine deficiency disorders have been controlled effectively,while the problem of iodine excess emerged.Because of different geographical environment,dietary habits and physiological status,some people did exposed to high level of iodine.In recent years,domestic and foreign scholars carried out series of researches aiming at disclose the effects of iodine excess on human health.The health problems induced by high iodine intaking are goiter,hyperthyroidism,hypothyroidism,autoimmune thyroiditis and thyroid cancer et al.Therefore,when preventing and treating iodine deficiency,iodine excess should also be avoided,so as to achieve the ideal goal of adjust measurements according to local conditions,classification guidance,and scientific iodine supplementation.

Poly (ADP-ribose) polymerase-1 and ischemic brain injury / 国际脑血管病杂志

Poly (ADP-ribose) polymerase-1 (PARP-1) is a ribozyme that widely exists in the cukaryotic cells.It plays important roles in the maintenance of genomic stability and the regulation of gene transcription and other physiological processes.PARP-1 is overactivated after ischemic brain injury,and PARP-1 gene knockout mice or PARP-1 inhibitor can reduce brain injury in a variety of models of cerebral ischemia.Therefore,PARP-1 plays important roles in the pathophysiologic processes of ischemic brain injury.The investigation of the effect of PARP-1 in cerebral ischemia contributes to further understanding the pathophysiologic mechanism of stroke and finding a new therapeutic target.

Stroke-induced immunological alterations and relevant treatment strategies / 国际脑血管病杂志

The changes of immune system following stroke mainly includes the local inflammatory responses of brain tissue and the systemic immunological changes, The former may exacerbate brain damage following stroke, the latter may increase the susceptibility to infection, and thus impact on brain function recovery and prognosis. Stroke interferes with the normal balance between the nervous system and the immune system, and its mechanism remains unclear. This article reviews the stroke-indnced immunological alterations and their mechanisms,as well as the corresponding treatment strategies in clinical practice.