Case-based learning method combined with mind mapping in pathophysiology teaching / 中华医学教育探索杂志

Objective:To explore the effect of case-based learning (CBL) combined with mind mapping on pathophysiology teaching.Methods:Totally 124 undergraduate students from Batch 2017 of Yanjing Medical College of Capital Medical University were selected as research subjects, and they were divided into experimental group ( n=60) and control group ( n=64). The traditional teaching method was used in the control group, while the experimental group adopted CBL combined with mind mapping teaching method. At the end of the course, the teaching effectiveness was evaluated by the usual grades from Mosoteach online teaching platform and test performances. SPSS 17.0 was used to perform Wilcoxon rank sum test and the Welch's correction t test. Results:The initiative of students in the experimental group was significantly improved than that in the control group ( P<0.001), and the understanding ability was also better in the experimental group than the control group ( P=0.020). The average theoretical scores of the experimental group were significantly better than those of the control group ( P=0.036), with the main manifestations that the scores of objective questions were higher than those of the control group ( P<0.001), and the scores of short answer and discussion questions were higher than those of the control group ( P=0.006). There was no significant difference in noun interpretation scores between the two groups ( P=0.302). Conclusion:The CBL combined with mind mapping can significantly improve the teaching quality of pathophysiology.

Impact of acute pancreatitis during pregnancy in Chinese women: a meta-analysis.

A random-effects meta-analysis was performed in English and Chinese databases since its inception to August 2020 to assess the incidence, causes and severity of acute pancreatitis (AP) at various stages of pregnancy, maternal and foetal mortality. A total of 154 articles representing 4034 patients with AP during pregnancy in China were included for the analysis. The incidence of AP during pregnancy was 0.0469 (95% confidence interval [CI], 0.0349; 0.0627) in the first trimester, whereas it was 0.2518 (95% CI, 0.2210; 0.2854) and 0.6323 (95% CI, 0.5870; 0.6753) in the second and third trimester, respectively. The major causes of AP were hypertriglyceridaemia (0.351 [95% CI, 0.3202; 0.3834]) and biliary pancreatitis (0.424 [95% CI, 0.4094; 0.5002]). The severity of AP was mild in majority of the patients. The incidence of AP at maternal mortality was 0.0184 (95% CI, 0.0126; 0.0269) and foetal mortality was 0.1018 (95% CI, 0.0867; 0.1192). Our meta-analysis revealed that hypertriglyceridaemia and biliary pancreatitis remain the major causes of AP during pregnancy. Foetal mortality requires further investigation. IMPACT STATEMENTWhat is already known on this subject? Acute pancreatitis (AP) in pregnant women is characterised by acute onset and delay in understanding the interaction of the metabolic changes with pancreatic pathophysiology, and thus becomes difficult to diagnose the disease and provide timely treatment to the patients. This poses a greater health risk among women and their foetus by increasing their chances of mortality.What the results of this study add? We performed an exhaustive, random-effects meta-analysis involving 154 articles representing 4034 patients to assess the incidence of AP at various stages of pregnancy, the causes of AP and the severity of AP during pregnancy, maternal and foetal mortality.What are the implications of these findings for clinical practice and/or further research? Our meta-analysis revealed that hypertriglyceridaemia and biliary pancreatitis remain the major causes of AP during pregnancy. Although the rates of maternal mortality have decreased in the recent years, foetal mortality still remains high and requires further investigation.

Acute Pancreatitis in Pregnancy: A Ten-Year Noninterventional, Retrospective Cohort Experience.

Background: The study is aimed at evaluating the clinical attributes, types, and risk factors associated with poor outcomes in women with acute pancreatitis (AP) during pregnancy. Methods: From 2011 to 2020, 45 antenatal mothers with AP were included in this noninterventional, retrospective study. The correlation between etiology of AP, its severity, biochemical parameters, length of stay, and treatment was analyzed. Based on the presence of organ failure and systemic complications, the severity of AP was classified according to the revised Atlantic criteria. Results: In total, 19 (42.2%), 15 (33.3%), and 11 (24.2%) patients had mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), respectively. The major cause of AP in these patients was hypertriglyceridemia (26.6%), while only 2 (4.44%) suffered from biliary pancreatitis. The median length of stay at hospital was significantly longer in patients with SAP (P = 0.034), and these patients had significantly higher triglycerides and total cholesterol levels when compared to MAP and MSAP. It was observed that levels of liver function enzymes such as alanine aminotransferase serum levels and aspartate aminotransferase serum levels were significantly higher in patients who stayed in hospital for >13 days. The presence of hypertriglyceridemia significantly increased the duration of stay (>13 days, P = 0.04) and induced SAP (P = 0.001). Majority of patients with SAP received blood purification than those with MAP and MSAP (P < 0.001). Conclusion: Hypertriglyceridemia was associated with AP during pregnancy in our study. Early diagnosis of AP and assessment of its severity are very important for the general management of this disease.

The effect of CAM comprehensive nursing interventions on the improvement of quality of life to patients with breast cancer and gynaecological tumours

Breastcancerin females, which is consideredthe most dreadfuldisease in India andthe worldas compared toother gynaecological cancers,demands extensive care and proper medicationin order to control itsprogressive growth. In addition to the conventional care ofthe patients, Complementary andAlternative Medicine(CAM)is administeredin a controlled way through proper guidance and counselling in orderto attainimprovedphysical andmental health forthe patients.Objective: The aim of the study wasto assess the effectiveness of CAMcomprehensive nursing interventionsand their benefit forpatients who havebreast cancer and gynaecological tumours.Methods: Statistical data was used to map the adult womendiagnosed with breast and gynaecological cancer and who were set to start new chemotherapy treatments. A total of 450 patients from different states of East India were enrolled in the studyover a period of four years. The patients wereselectedbased on their preference for undergoing CAM.The research was conducted usingacross-sectionalanonymous self-administered questionnaireto examine women's perspectivestowards the use of CAM and itseffect on their mental andphysical health.Results:42%of the women preferred theuseofCAM astheir alternative treatment. Breast cancer patients disclosed that 48.1% of them had used CAM and 39% of women with gynaecological cancersstated that they had usedCAM. The results further indicated a less frequent deteriorationin the health of CAM users(38.4%) thantonon-users(55%). In terms of those who utilizedvitamins and nutritional diets,60% of the participants reported using a proper diet, including antioxidants, minerals, vitamins and herbs etc. 37% opted for spiritual healing through yoga, 26% utilized energy healing, 42.4% utilized acupuncture,72% preferred massagesand 23% of patients utilized chiropractic methods.The use of CAM was foundmainlyin the patients with proper education and awareness and those with a family history of cancer who were not receiving the necessary care from their previous primary physician.Conclusion:CAM still requiresextensive research in terms of its applications in dealing with patients and in orderto successfully launch programmes aimed at promoting its useworldwide andto eradicate all the other false notions about it.[Ethiop. J. Health Dev. 2022; 36(2):000-000]Keywords: Breast Cancerand gynaecological tumours,Complementary And Alternative Medicine (CAM), Complementary Oncology,Quality Of Life, Nutritional Diet and Spiritual Healing, HRQL (Health-Related Quality Of Life).IntroductionCancer has been the primaryconcern in Indiafrom the onset,resulting in thousands of deaths due to the lack of adequatemedication and therapy.Breast cancer is considered to bea common invasive form of cancer which is responsible for the second highest mortality rate among the primaryfatal conditions of cancer-causing deaths in women. Under the National Cancer Registry Program,the breast, cervix, uteri,and oral cavity(7)are the most common cancer sitesin women. According to statistics, 50-60% of all cancers amongIndian women are commonly found inthe cervix uteri, breast, corpus uteri and ovaries,which are the main organs forcancer invasion. The percentage of women who experience these types of cancer is increases, with more women becoming susceptible to breast cancer, in women up to 3-8% suffer fromovarian cancer,0.5-4.8%have cancer of the corpus uteri, 1-3% have vulva and/or gestational trophoblastic tumours and a staggering75,000 or more women have breast cancer. With the advancements of the disease through time,research programs were also improved in order to enable the improvement of existing measures and/or the development of new measures aimed at combating the diseas and decreasing mortality rates. Apart from the conventional chemotherapy technique,various other programs have been introduced andencorporated into treatment regimes in order to improve the lives of those who are affected by cancer.Complementary andAlternative Medicine (CAM) emphasizesthe methods and practices that are therapeutic and which help diagnose or curethe disease,these methods are intended tocomplement the conventional methods and can be used in place of mainstream medicine. Women with breast cancer and other gynaecological tumoursare increasingly inclined towards the use of CAM. With the increasing number of cancer reports in Indiaand the world,and with the principal amount leading to mortality, women with proper education and awareness are inclined to choosealternative methods rather than the old conventional ones. The side-effects resulting from the chemotherapy are immense and toxic,which is one of the reasons women are inclined to choose.Various research projects and cumulative studies have been conducted in order to review and discoverthe

A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope

With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by historical SARS-CoV-2 strains, others induced escape variants in vivo and lost activity against emerging strains. We identified one mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of inhibitory antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques

The deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.

The differential diagnosis of pancreatic acinar cell carcinoma and pancreatic ductal adenocarcinoma based on multidetector computed tomography features / 中华胰腺病杂志

Objective:To explore the differential diagnosis of pancreatic acinar cell carcinoma (PACC) and pancreatic ductal adenocarcinoma (PDAC) based on multidetector computed tomography (MDCT) features.Methods:The clinical, pathological and MDCT imaging data of 26 patients with pathologically confirmed PACC and 145 patients with pathologically confirmed PDAC who underwent MDCT from November 2013 to April 2021 were retrospectively studied. The differences of MDCT features including tumor location, tumor size, common pancreatic duct and bile duct dilatation, pancreatitis, lymph node metastasis, cyst, pancreatic parenchyma atrophy, duodenal involvement, bile ductal and vascular involvement between the two groups were compared. Univariate analysis and multivariate analysis by logistic regression models were performed to identify the independent predictive factors for PACC.Results:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement were significantly different between PACC group and PDAC group (all P value<0.05). Multivariate analysis revealed that the tumor size ( OR=1.07, 95% CI 1.028-1.15, P=0.001), lymph node metastasis ( OR=0.23, 95% CI 0.065-0.800, P=0.02), pancreatic parenchyma atrophy ( OR=0.15, 95% CI 0.048-0.490, P=0.002) were closely associated with PACC. Conclusions:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement evaluated by MDCT had a certain value in differentiating PACC from PDAC, and the tumor size, lymph node metastasis and pancreatic parenchyma atrophy were independent predictors for the diagnosis of PACC.

Correlation between MDCT-based arterial radiomics score and the resection margin of superior mesenteric vein in patients with pancreatic head cancer / 中华胰腺病杂志

Objective:To accurately identify the relationship between the arterial radiomics score (rad-score) and pathologic superior mesenteric vein (SMV) resection margin in patients with pancreatic head cancer.Methods:The clinical data of 181 patients with pathologically confirmed pancreatic head cancer, who underwent multi-slice computed tomography (MDCT) within one month of resection in the First Affiliated Hospital of Naval Medical University between January 2016 and December 2018 were collected. Based on the pathology of SMV resection margin, the patients were divided into SMV negative margin group ( n=127) and SMV positive margin group ( n=54). The clinical, pathological and radiological features were compared between two groups. 3D slicer software was used to draw the region of interest in each layer of the primary CT arterial images for tumor segmentation. Rython package was applied to extract the radiomics features of pancreatic tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculated the arterial rad-score. Univariate and multivariate logistic regression models were used to analyze the association between the arterial rad-score and SMV resection margin. ROC was drawn and AUC, sensitivity, specificity and accuracy for diagnosing the SMV resection margin were calculated. The clinical usefulness of arterial rad-score for diagnosing SMV resection margin was determined by decision curve analysis (DCA). Results:There were statistical differences on LVSI and the touching angle of tumor and SMV/portal vein (PV) between SMV negative margin group and SMV positive margin group (all P<0.001). A total of 1 029 arterial radiomics CT features were obtained, and 14-selected arterial phase features associated with SMV resection margin were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, LVSI, the touching angle of tumor and SMV/PV were all correlated with SMV resection margin (all P<0.001). Multivariate analyses confirmed that patients with high arterial radiomics score had a 3.63-fold risk of positive resection margin compared with that with low arterial radiomics score, and a higher arterial rad-score was associated with a higher risk of SMV positive resection margin ( P<0.0001). At the cut-off value of -0.711, AUC of the arterial rad-score for diagnosing SMV resection margin was 0.838, and the sensitivity, specificity and accuracy was 77.8%, 75.6% and 76.24%. Decision curve analysis demonstrated that the percentage of the arterial radiomics score for predicting the positive SMV resection margin was >0.02, and the application of the arterial radiomics score could benefit the patients. Conclusions:The arterial rad-score was strongly correlated with SMV resection margin of pancreatic cancer, and can accurately predict SMV resection margin and provide a new tool for preoperative noninvasive evaluation of the SMV resection margin.

ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors / 神经科学通报·英文版

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch–aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch–aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

Characteristics and influencing factors of esophageal stenosis after endoscopic submucosal dissection for early esophageal carcinoma / 中华消化内镜杂志

Objective:To investigate the characteristics and influencing factors of esophageal stenosis after endoscopic submucosal dissection (ESD) for early esophageal carcinoma.Methods:Patients who underwent ESD in the Digestive Endoscopy Center of the Second Affiliated Hospital of Army Medical University from January 2011 to December 2018 were included. The data were obtained from medical records and follow-up. The influencing factors of stenosis were determined by single factor and Cox regression analysis.Results:A total of 654 patients underwent ESD and 79 (12.1%) of them developed postoperative esophageal stenosis. The median time of stenosis development was 27 (17, 43) days. The morphology and lesion circumferential proportion were independent factors for the occurrence of stenosis after ESD. The stenosis incidence of type Ⅱa was 6.601 times (95% CI: 1.518-28.709, P=0.012) compared with that of type Ⅱc. The incidence of stenosis in lesions with 75%-<100% and 100% circumference was 17.408 times (95% CI: 8.009-37.839, P<0.001)and 52.439 times (95% CI: 23.905-115.029, P<0.001) respectively compared with that of patients <75%. Among the 79 patients, 27 had severe stenosis, and the lesion circumferential proportion was an independent factor for stenosis. Compared with the group of lesion circumferential proportion of less than 75%, the incidences of stenosis of lesion circumferential proportion of 75%-<100% and 100% were 7.775 (95% CI: 1.977-30.577, P=0.003) and 70.062 (95% CI: 19.879-246.926, P<0.001) times respectively. Conclusion:The morphology and lesion circumferential proportion are two independent factors for the occurrence of esophageal stenosis after ESD. Additionally, lesion circumferential proportion is an independent factor for the occurrence of severe esophageal stenosis after ESD.

ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors / 神经科学通报·英文版

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

Clinical effects of two different enteral nutritional emulsions in elderly patients with severe pneumonia / 中华老年医学杂志

Objective:To compare the clinical effects of two enteral nutritional emulsions, TP-HE and TPF, in elderly patients with severe pneumonia.Methods:This was a randomized study with contemporaneous controls.A total of 56 elderly patients over 65 years old who met the diagnostic criteria for severe pneumonia and were receiving insulin were enrolled.They were randomly divided into the observation group(n=28, enteral TPF-HE at a uniform rate through a nasogastric tube)and the control group(n=28 cases, enteral TPF at a uniform rate through a nasogastric tube). The total daily energy supply was calculates based on the ideal weights of patients.Prealbumin(PA), serum albumin(ALB), body mass index(BMI)and hemoglobin(Hb)were continuously measured at 1, 2, 3, 4, 5, 6 and 7 days after treatment.The effects of the enteral nutritional emulsions in elderly patients with severe pneumonia were analyzed by using repeated measures analysis of variance in a general linear model.Results:There was no significant difference in PA(244.5±55.1)mg/L vs.(237.8±40.4)mg/L, ALB(37.6±5.6)mg/L vs.(38.3±5.5)mg/L, BMI(21.9±0.2)kg/m 2vs.(22.4±0.2)kg/m 2)or Hb(104.4±26.8)mg/L vs.(103.6±25.6)mg/L between the TP-HE group and the TPF group before admission( P>0.05). The energy received from the enteral nutritional emulsions was not significantly different between the TP-HE group and the TPF group(79.8±4.8)kcal/d vs.(79.3±6.6)kcal/d( P>0.05). PA and serum ALB levels had significant differences between the TP-HE group and the TPF group at 1, 2, 3, 4, 5, 6 and 7 days after treatment( P<0.01 or 0.05). Increases in PA and serum ALB levels varied at certain time points between the TP-HE group and the TPF group.Hb levels had no significant difference at 1 and 2 days( P>0.05), but were significantly different at other time points between the two groups( P<0.01). There was no significant difference in BMI between the two groups( F=1.709, P>0.05). Conclusions:Both of the enteral nutrition emulsions can improve PA, ALB and Hb levels, with TP-HE offering more significant effects on PA, ALB and Hb levels.There is no difference in BMI at any time point whether patients receive TP-HE or TPF.

A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters.

The development of an effective vaccine against SARS-CoV-2, the etiologic agent of COVID-19, is a global priority. Here, we compared the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in Golden Syrian hamsters. While immunization with ChAd-SARS-CoV-2-S induced robust spike protein specific antibodies capable or neutralizing the virus, antibody levels in serum were higher in hamsters immunized by an intranasal compared to intramuscular route. Accordingly, ChAd-SARS-CoV-2-S immunized hamsters were protected against a challenge with a high dose of SARS-CoV-2. After challenge, ChAd-SARS-CoV-2-S-immunized hamsters had less weight loss and showed reductions in viral RNA and infectious virus titer in both nasal swabs and lungs, and reduced pathology and inflammatory gene expression in the lungs, compared to ChAd-Control immunized hamsters. Intranasal immunization with ChAd-SARS-CoV-2-S provided superior protection against SARS-CoV-2 infection and inflammation in the upper respiratory tract. These findings support intranasal administration of the ChAd-SARS-CoV-2-S candidate vaccine to prevent SARS-CoV-2 infection, disease, and possibly transmission.

Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization

Although neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of COVID-19 vaccines and have received emergency use authorization as therapeutics, viral escape mutants could compromise their efficacy. To define the immune-selected mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) to generate 50 different escape mutants. The variants were mapped onto the RBD structure and evaluated for cross-resistance to mAbs and convalescent human sera. Each mAb had a unique resistance profile, although many shared residues within an epitope. Some variants (e.g., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g., E484K) escaped neutralization by convalescent sera, suggesting some humans induce a narrow repertoire of neutralizing antibodies. Comparing the antibody-mediated mutational landscape in S with sequence variation in circulating SARS-CoV-2, we define substitutions that may attenuate neutralizing immune responses in some humans.

A single intranasal dose of chimpanzee adenovirus-vectored vaccine confers sterilizing immunity against SARS-CoV-2 infection

The Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.

Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion

Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protein catalyzed membrane fusion. Our results highlight a unique antiviral mechanism of 25HC and provide the molecular basis for its possible therapeutic development.

Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2.

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly disrupt epidemic transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, yet there is no consensus as to which assay should be used for such measurements. Using an infectious molecular clone of vesicular stomatitis virus (VSV) that expresses eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput imaging-based neutralization assay at biosafety level 2. We also developed a focus reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. We compared the neutralizing activities of monoclonal and polyclonal antibody preparations, as well as ACE2-Fc soluble decoy protein in both assays and find an exceptionally high degree of concordance. The two assays will help define correlates of protection for antibody-based countermeasures including therapeutic antibodies, immune {gamma}-globulin or plasma preparations, and vaccines against SARS-CoV-2. Replication-competent VSV-eGFP-SARS-CoV-2 provides a rapid assay for testing inhibitors of SARS-CoV-2 mediated entry that can be performed in 7.5 hours under reduced biosafety containment.

Association between resting heart rate trajectory pattern and risk of cardiovascular and cerebrovascular diseases / 中华心血管病杂志

Objective@#To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of cardiovascular and cerebrovascular diseases (CVDs).@*Methods@#This prospective cohort study included 63 040 participants who took part in the health examination in 2006 and one of the health examinations on 2008 or 2010 and were free of myocardial infarction, stroke, arrhythmia, cancer and not treated with β-recepter blocker. The outcomes were the first occurrence of myocardial infarction and stroke during the follow up ended on December 31, 2015. RHRs were measured in 2006, 2008, and 2010. We used latent mixture modeling SAS Proc procedure to identify RHR trajectories. We identified 4 distinct RHR trajectory patterns based on the data derived from 2006 and on the pattern change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing). Collected the general clinical data of the patients. Cox regression model was used to determine the association between RHR trajectory patterns and the risk of CVDs during follow up. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling.@*Results@#There were statistical significance among the 4 distinct RHR trajectory patterns on the following variables: age, gender, smoking status, drinking status, physical activity, education status, history of use antihypertensive drugs, history of hypertension,history of diabetes, body mass index, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and the level of high-sensitivity C-reactive protein (all P<0.01). The moderate-increasing pattern experienced the highest risk of developing stroke and CVDs among all 4 patterns. The cumulative incidence of cerebral infarction, cerebral hemorrhage and CVDs in the order of low-stable trajectory, moderate-stable trajectory and moderate-increasing trajectory. The cumulative incidences of cerebral infarction, cerebral hemorrhage and CVDs in elevated-decreasing trajectory group were significantly lower than those in moderate-increasing trajectory group, but higher than those in moderate-stable trajectory group. Compared to the low-stable pattern, adjusted HR was 1.3 (95%CI 1.0-1.6) for the moderate-increasing pattern after adjustment for potential confounders.@*Conclusion@#Our study finds that individuals with moderate-increasing RHR trajectory pattern are associated with higher risk of cardiovascular and CVDs.

Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is Not Superior to Unmodified BMSCs.

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip disorder, and it threatens patients who require megadose of steroid therapies. Nowadays, no valid therapies can reverse the development of GC-induced ONFH once it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice. Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1 (Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway, could be an explanation. Thus, the aim of the present work lies in investigating the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1 interference in preventing the progression of the GC-induced ONFH. Lentivirus-meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone (10-6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and afterwards prompted the transduction of Wnt/ß-catenin in which the Runx2 and PPARγ were upregulated and downregulated, respectively. Thus, the osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference, and the progression of the disease was prevented. However, the effects were not significantly superior to treatment with nongenetically modified or normal BMSCs.