Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in th...Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality.The increased prevalence of allergic airway disease worldwide can be partially a...Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality.The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes.Climate change and air pollution pose adverse impacts on respiratory allergies,and that the mechanisms are complex and interactive.Adverse weather conditions,such as extreme temperatures,can act directly on the respiratory tract to induce allergic respiratory illnesses.Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution,and therefore indirectly enhance health risks.Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation,and the rising temperatures and CO2 increase pollen,molds,and spores,which escalate the risk of allergic respiratory diseases.The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants,which in turn augment the allergenicity of aeroallergens.With the Earth’s climate change,migration of humans and plants shift the living environments and allergens of susceptible people.Urban residents are exposed to multiple factors while children are sensitive to environmental exposure.Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases,health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.展开更多
脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊...脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊断需要不断改变来满足临床和研究的要求。然而,尽管有许多新型的生物标记和筛选工具去预测脓毒症发生的风险,但是这些措施的诊断价值和有效性不足以让人满意,并且没有充分的证据去建议临床使用这些新技术。因此,脓毒症的临床诊断标准需要定期更新去适应不断产生的新证据。这篇综述旨在呈现当前脓毒症的诊断和早期识别方面的最新研究证据。临床运用不同的诊断方法的推荐意见依赖于推荐、评价、发展和评估分级体系(Grades of Recommendation Assessment,Development and Evaluation,GRADE),因为大部分的研究是观察性研究,并没有对这些方法进行可靠评估,采用的是两步推理方法。未来需要更多研究来确认或者反驳某一特殊的指标检测,同时应该直接采用相关病人的结果数据。展开更多
The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnos...The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilat展开更多
Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chines...Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chinese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Chinese male population. Data were collected from 893 Chinese male referrals, 697 in the derivation set and 196 in the external validation set, who underwent initial prostate biopsies as individual screening. We analyzed age, prostate volume, total prostate-specific antigen （PSA）, PSA density （PSAD）, digital rectal examinations （DRE） and transrectal ultrasound （TRUS） echogenicity. Logistic regression analysis estimated odds ratio, 95% confidence intervals and Pvalues. Independent predictors of a positive biopsy result included advanced age, small prostate volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver-operating characteristic curve for the model was 88.8%, which was greater than that of the prediction based on total PSA alone （area under the receiver-operating characteristic curve 74.7%）. If externally validated, the predictive probability was 0.827 and the accuracy rate was 78.1%, respectively. Incorporating clinical and laboratory data into a prebiopsy nomogram improved the prediction of prostate cancer compared with predictions based solely on the individual factors.展开更多
Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web o...Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB 展开更多
Ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),also known as lysine(K)-specific demethylase 6A(KDM6A),functions as a tumor suppressor gene or oncogene depending on the tumor type and context.Ho...Ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),also known as lysine(K)-specific demethylase 6A(KDM6A),functions as a tumor suppressor gene or oncogene depending on the tumor type and context.However,its tumor-suppressive mechanisms remain largely unknown.Here,we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma(PDA)and determined the potential mechanisms of its dysregulation.UTX expression and its association with clinicopathologic characteristics of PDA patients were analyzed using immunohistochemistry.UTX mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot analyses.The biological functions of UTX in PDA cell growth,migration,and invasion were determined using gain-and loss-of-function assays with both in vitro and in vivo animal models.UTX expression was reduced in human PDA cell lines and specimens.Low UTX expression was associated with poor differentiation and prognosis in PDA.Forced UTX expression inhibited PDA proliferation,migration,and invasion in vitro and PDA growth and metastasis in vivo,whereas knockdown of UTX expression did the opposite.Mechanistically,UTX expression was trans-activated by GATA6 activation.GATA6-mediated PDA progression could be blocked,at least partially,by silencing UTX expression.In conclusion,loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and metastasis.Thus,UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target.展开更多
Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80...Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 groups.Groups included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT gait.DT cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of covariance.Then a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration.Results:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait outcomes.Conclusion:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.展开更多
BACKGROUND Health utility assessments have been developed for various conditions,including chronic liver disease.Health utility scores are required for socio-economic evaluations,which can aid the distribution of nati...BACKGROUND Health utility assessments have been developed for various conditions,including chronic liver disease.Health utility scores are required for socio-economic evaluations,which can aid the distribution of national budgets.However,the standard health utility assessment scores for specific health conditions are largely unknown.AIM To summarize the health utility scores,including the EuroQOL 5-dimensions 5-levels(EQ-5D-5L),EuroQol-visual analogue scale,short from-36(SF-36),RAND-36,and Health Utilities Index(HUI)-Mark2/Mark3 scores,for the normal population and chronic liver disease patients.METHODS A systematic literature search of PubMed and MEDLINE,including the Cochrane Library,was performed.Meta-analysis was performed using the RevMan software.Multiple means and standard deviations were combined using the StatsToDo online web program.RESULTS The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C.HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients.CONCLUSION The EQ-5D-5L is the most popular questionnaire for health utility assessments.Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.展开更多
AIM： A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue （MALT） lymphomas remain Helicobacter pylori （ H pylori）-dependent. However,unlike their low-grade counterparts, high-grad...AIM： A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue （MALT） lymphomas remain Helicobacter pylori （ H pylori）-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori- spedfic intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 （B7.2） and the infiltration of CD56 （＋） natural killer （NK） cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT iymphoma.METHODS： Lymphoma biopsies from 26 patients who had participated in a prospective study of Hpylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less alter H pylori eradication were dassified as H pylori-dependent; others were dassified as H pylori-dependent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS： There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 （68.8%） of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases （P = 0.001）.H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 （＋） NK cells than H pylori-independent cases （2.8±1.4% vs 1.1±0.8%, P = 0.003）. CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 （＋） NK cells compared to CD86-negative cases （2.9±1.1% vs 1.4±1.3%; P= 0.005）.CONCLUSION： These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with Hpylori-dependent state of early-stage high-grade展开更多
Rationale:The mechanism of sudden cardiac death in COVID-19 can be multifactorial.Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases.Cytokine storm syndrome and idiosyncra...Rationale:The mechanism of sudden cardiac death in COVID-19 can be multifactorial.Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases.Cytokine storm syndrome and idiosyncratic reaction with mesalazine use may lead to sudden cardiac death in COVID-19.Use of immunosuppressants in hospitalized COVID-19 patients should be continued with caution,especially in patients with inflammatory bowel disease.Patient’s concern:A 75-year-old man who was tested positive for SARS-CoV-2 was admitted with a history of shortness of breath for the last two days.He was a known case of Crohn’s disease treated with mesalazine.Diagnosis:COVID-19 pneumonia with underlying Crohn’s disease leading to sudden cardiac death.Intervention:Remdesivir,antibiotics,steroids,low molecular weight heparin,tablet zinc,tab vitamin C,and other supportive treatment were started.Because of increased inflammatory markers,itolizumab was given to the patient on the 2nd day.Outcome:On the 5th day of the intensive care unit,the patient complained of sudden chest pain with respiratory distress leading to bradycardia and asystole and could not be resuscitated.Lessons:Causes for sudden cardiac death in COVID-19 pneumonia patients with Crohn’s disease is multifactorial.Although mesalazine may be a safe and effective drug in the management of inflammatory bowel disease,it can induce sytokine strom syndrome and idiosyncratic reactions that could be one of the reasons of sudden cardic death.Therefore,we should be aware of its serious and potentially life-threatening complications,especially in COVID-19 infected patients.展开更多
Background:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis,partially by activating lung fibroblasts.However,how macrophages communicate with lung fibroblasts is largely unexplored.Exosome...Background:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis,partially by activating lung fibroblasts.However,how macrophages communicate with lung fibroblasts is largely unexplored.Exosomes can mediate intercellular communication,whereas its role in lung fibrogenesis is unclear.Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo,bleomycin(BLM)-induced lung fibrosis model was established and macrophages infiltration was examined.The effects of GW4869,an exosomes inhibitor,on lung fibrosis were assessed.Moreover,macrophage exosomes were injected into mice to observe its pro-fibrotic effects.In vitro,exosomes derived from angiotensin Ⅱ(Ang Ⅱ)-stimulated macrophages were collected.Then,lung fibroblasts were treated with the exosomes.Twenty-four hours later,protein levels ofα-collagen I,angiotensin Ⅱ type 1 receptor(AT1R),transforming growth factor-β(TGF-β),and phospho-Smad2/3(p-Smad2/3)in lung fibroblasts were examined.The Student's t test or analysis of variance were used for statistical analysis.Results:In vivo,BLM-treated mice showed enhanced infiltration of macrophages,increased fibrotic alterations,and higher levels of Ang Ⅱ and AT1R.GW4869 attenuated BLM-induced pulmonary fibrosis.Mice with exosomes injection showed fibrotic features with higher levels of Ang Ⅱ and AT1R,which was reversed by irbesartan.In vitro,we found that macrophages secreted a great number of exosomes.The exosomes were taken by fibroblasts and resulted in higher levels of AT1R(0.22±0.02 vs.0.07±0.02,t=8.66,P=0.001),TGF-β(0.54±0.05 vs.0.09±0.06,t=10.00,P<0.001),p-Smad2/3(0.58±0.06 vs.0.07±0.03,t=12.86,P<0.001)andα-collagen I(0.27±0.02 vs.0.16±0.01,t=7.01,P=0.002),and increased Ang Ⅱ secretion(62.27±7.32 vs.9.56±1.68,t=12.16,P<0.001).Interestingly,Ang Ⅱ increased the number of macrophage exosomes,and the protein levels of Alix(1.45±0.15 vs.1.00±0.10,t=4.32,P=0.012),AT1R(4.05±0展开更多
As the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to spread globally,it became evident that the SARS-CoV-2 virus infects multiple organs including the brain.Several clinical studies revealed ...As the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to spread globally,it became evident that the SARS-CoV-2 virus infects multiple organs including the brain.Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes.Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood,several theories have been suggested including direct and indirect pathways induced by the virus.One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route.Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells.Nevertheless,the indirect mechanisms,including blood-clotting abnormalities and prolonged activation of the immune system,can result in further tissue and organ damages seen during the course of the disease.This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.展开更多
Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel...Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.展开更多
Objective To explore the clinical and radiological features of severe acute respiratory syndrome (SARS).Methods Analysis of the clinical presentation, chest radiographs, course of disease and features of severe pneumo...Objective To explore the clinical and radiological features of severe acute respiratory syndrome (SARS).Methods Analysis of the clinical presentation, chest radiographs, course of disease and features of severe pneumonia in 45 SARS patients diagnosed at our hospital in Beijing between April 5 - 20, 2003. Also included is a summation of the clinical features of SARS.Results (1) SARS appears to have high infectivity; (2) the most common symptom is fever; (3) the count of leukocyte is normal or decreased; (4) most patients (35/45, 77.8%) had experienced a 24-hour fever prior to the abnormal chest X-ray changes which showed progression of pulmonary infiltrates within 48 hours in 71.1% (32/45) of the patients and, (5) the percentage of patients who developed severe pneumonia (24. 4%) is higher than those who developed typical pneumonia.Conclusion SARS is a disease with high infectivity and has its own clinical and radiological features. Early recognition, prompt isolation, and appropriate therapy are the key to combate this infection.展开更多
Glycosylation of mucins mediated by N-acetylgalactosaminyltransferases(GALNTs)is closely related to respiratory diseases such as asthma and chronic obstructive pulmonary disease(COPD).In addition,long non-coding RNAs(...Glycosylation of mucins mediated by N-acetylgalactosaminyltransferases(GALNTs)is closely related to respiratory diseases such as asthma and chronic obstructive pulmonary disease(COPD).In addition,long non-coding RNAs(LncRNAs)participate in physiological and pathological processes through various epigenetic mechanisms.In this study,we found that a novel LncRNA named NKILA combined with multiple mucins and GALNTs potentially by several bioinformatics methods,and we used quantitative real-time PCR(RT-qPCR)to detect the expressions of NKILA,MUC5AC,MUC5B,and GALNT2 mRNA in 50 cases of asthma samples and 19 cases of normal samples,whose results showed that the expression of NKILA was significantly decreased in asthmatic samples,negatively correlated with the severity of asthma and the expressions of MUC5AC and MUC5B,while GALNT2 was significantly increased in asthmatic tissues,and positively correlated with the severity of asthma and the expressions of MUC5AC and MUC5B.In vitro,we used transient transfection technology to overexpress or interfere with NKILA and GALNT2 and then detected the expressions of MUC5AC and MUC5B via RT-qPCR and Western blot,which demonstrated GALNT2 can promote the expressions of MUC5AC and MUC5B protein,while NKILA could inhibit this effect.Furthermore,co-immunoprecipitation results showed that GALNT2 could bind to MUC5AC and MUC5B protein.RNA immunoprecipitation and RNA pull-down experiments showed that NKILA could bind to GALNT2.These evidences suggested that there are correlations among the expression of NKILA,GALNT2,MUC5AC,and MUC5B proteins in asthmatic patients.Mechanically,we concluded that NKILA can suppress the O-linked glycosylation of MUC5AC and MUC5B proteins by binding to GALNT2 and inhibit the expression of MUC5AC and MUC5B proteins.Our researches provided a potential therapeutic target for AHR.展开更多
Age determination is one of the most important factors for identification. Unfortunately, births are not recorded regularly in Sudan, especially in rural areas. However, identification of age is very important for a v...Age determination is one of the most important factors for identification. Unfortunately, births are not recorded regularly in Sudan, especially in rural areas. However, identification of age is very important for a variety of reasons, including identifying legal and criminal responsibility, and for many other social events such as beginning a job, marriage, retirement and joining the army. The study aimed to find the reliability of using international methods to estimate bone age of people through hand bone radiograph in Sudanese people by studying the reliability of using hand bone age “the digital atlas of hand age” which depended on Greulich and Pyle (GP) and Tanner and Whitehouse (TW2/3) methods in Sudanese people in exact group of age, and to compare the hand and wrist bone development between Caucasian and Sudanese people. The study was conducted on 48 samples (26 males and 22 females) from the center of Sudan. The study was made by conventional X-Ray taken from Sudanese newborn babies to 2 and 3 years old for males and females respectively. Those images were taken mostly from the emergency and orthopedic outpatient departments. The ages were grouped in the same ways and periods used in the atlas. So the criteria were tested, and the outcomes were compared with international standards in the atlas of hand bone age. There is evidence that skeletal maturation may vary between difference ethnic and socioeconomic groups of children or among children living in various geographical locations. It is found that there is reliability and applicability of using the atlas in Sudanese people with considering that there might be mild variations between Sudanese and Caucasian people’s hand and wrist bone development in which Caucasian people bone growth was earlier than the Sudanese people bones about 1 - 2 months.展开更多
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
基金This work was supported by the grant from the National Key Research and Development Program of China(No.2018YFA0606200).
文摘Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality.The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes.Climate change and air pollution pose adverse impacts on respiratory allergies,and that the mechanisms are complex and interactive.Adverse weather conditions,such as extreme temperatures,can act directly on the respiratory tract to induce allergic respiratory illnesses.Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution,and therefore indirectly enhance health risks.Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation,and the rising temperatures and CO2 increase pollen,molds,and spores,which escalate the risk of allergic respiratory diseases.The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants,which in turn augment the allergenicity of aeroallergens.With the Earth’s climate change,migration of humans and plants shift the living environments and allergens of susceptible people.Urban residents are exposed to multiple factors while children are sensitive to environmental exposure.Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases,health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.
文摘脓毒症是一种由感染引起的异质性疾病,感染触发了一系列复杂的局部或者全身的免疫炎症反应,引起多器官功能衰竭,发病率和病死率显著升高。由于至今仍然没有诊断脓毒症的金标准,所以脓毒症的临床诊断仍是一个难题。因此,脓毒症的临床诊断需要不断改变来满足临床和研究的要求。然而,尽管有许多新型的生物标记和筛选工具去预测脓毒症发生的风险,但是这些措施的诊断价值和有效性不足以让人满意,并且没有充分的证据去建议临床使用这些新技术。因此,脓毒症的临床诊断标准需要定期更新去适应不断产生的新证据。这篇综述旨在呈现当前脓毒症的诊断和早期识别方面的最新研究证据。临床运用不同的诊断方法的推荐意见依赖于推荐、评价、发展和评估分级体系(Grades of Recommendation Assessment,Development and Evaluation,GRADE),因为大部分的研究是观察性研究,并没有对这些方法进行可靠评估,采用的是两步推理方法。未来需要更多研究来确认或者反驳某一特殊的指标检测,同时应该直接采用相关病人的结果数据。
基金supported(in part)by the National Key Research and Development Program of China(2020YFC0845500)the Special Project for Emergency of Hubei Province(2020FCA008)the First Level Funding of the Second Medical Leading Talent Project in Hubei Province。
文摘The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilat
文摘Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chinese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Chinese male population. Data were collected from 893 Chinese male referrals, 697 in the derivation set and 196 in the external validation set, who underwent initial prostate biopsies as individual screening. We analyzed age, prostate volume, total prostate-specific antigen （PSA）, PSA density （PSAD）, digital rectal examinations （DRE） and transrectal ultrasound （TRUS） echogenicity. Logistic regression analysis estimated odds ratio, 95% confidence intervals and Pvalues. Independent predictors of a positive biopsy result included advanced age, small prostate volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver-operating characteristic curve for the model was 88.8%, which was greater than that of the prediction based on total PSA alone （area under the receiver-operating characteristic curve 74.7%）. If externally validated, the predictive probability was 0.827 and the accuracy rate was 78.1%, respectively. Incorporating clinical and laboratory data into a prebiopsy nomogram improved the prediction of prostate cancer compared with predictions based solely on the individual factors.
文摘Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB
基金supported by the Jiangxi Science Fund for Distinguished Young Scholars(China)(No.20212ACB216012)the Funding Program for Academic and Technical Leaders of Main Subjects in Jiangxi Province,China(No.20213BCJ22009 to H.Q.Zhang)+4 种基金the National Natural Science Foundation of China(No.81460372 to H.Q.Zhang,No.81960528 to S.Zheng)the Hainan Province Science and Technology special fund(China)(ZDYF2020132 to S.Zheng)the Innovation Platform for Academicians of Hainan Province(China)(YSPTZX202208 to S.Zheng)Hainan Province Clinical Medical Center(QWYH2021276)the Cardiovascular Disease Research Science Innovation Group of Hainan Medical University(China).
文摘Ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),also known as lysine(K)-specific demethylase 6A(KDM6A),functions as a tumor suppressor gene or oncogene depending on the tumor type and context.However,its tumor-suppressive mechanisms remain largely unknown.Here,we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma(PDA)and determined the potential mechanisms of its dysregulation.UTX expression and its association with clinicopathologic characteristics of PDA patients were analyzed using immunohistochemistry.UTX mRNA and protein expression and their regulation in PDA cell lines were measured using quantitative polymerase chain reaction and Western blot analyses.The biological functions of UTX in PDA cell growth,migration,and invasion were determined using gain-and loss-of-function assays with both in vitro and in vivo animal models.UTX expression was reduced in human PDA cell lines and specimens.Low UTX expression was associated with poor differentiation and prognosis in PDA.Forced UTX expression inhibited PDA proliferation,migration,and invasion in vitro and PDA growth and metastasis in vivo,whereas knockdown of UTX expression did the opposite.Mechanistically,UTX expression was trans-activated by GATA6 activation.GATA6-mediated PDA progression could be blocked,at least partially,by silencing UTX expression.In conclusion,loss of GATA6-mediated UTX expression was evident in human PDA and restored UTX expression suppressed PDA growth and metastasis.Thus,UTX is a tumor suppressor in PDA and may serve as a prognostic biomarker and therapeutic target.
基金funded in part by the University of Delaware Unidel Distinguished Graduate Scholars FellowshipDepartment of Kinesiology and Applied Physiology Doctoral Research Fund+2 种基金funding support in part by the Department of Defense grant W81XWH-21-1-0590the Penn Injury Science CenterNational Institutes of Health/National Institute of Neurological Disorders and Stroke brain injury training grant T32 NS043126。
文摘Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 groups.Groups included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT gait.DT cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of covariance.Then a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration.Results:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait outcomes.Conclusion:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.
基金Supported by Grants-in-Aid from JSPS KAKENHI,No.JP 20K10404(to Mizuguchi T)and No.JP 21K10715(to Ishinuki T)the Hokkaido Hepatitis B Litigation Orange Fund,No.2059198(to Mizuguchi T)and No.2136589(to Harada K)+14 种基金Terumo Life Science Foundation,No.2000666Pfizer Health Research Foundation,No.2000777the Viral Hepatitis Research Foundation of Japan,No.3039838Project Mirai Cancer Research Grants,No.202110251Takahashi Industrial and Economic Research Foundation,No.12-003-106Daiichi Sankyo Company,No.2109540Shionogi and Co.,No.2109493MSD,No.2099412Takeda Pharmaceutical Company,No.2000555Sapporo Doto Hospital,No.2039118Noguchi Hospital,No.2029083Doki-kai Tomakomai Hospital,No.2059203Tsuchida Hospital,No.2000092Shinyu-kai Noguchi Hospital,No.2029083(to Mizuguchi T)the Yasuda Medical Foundation,No.28-1(to Ishinuki T).
文摘BACKGROUND Health utility assessments have been developed for various conditions,including chronic liver disease.Health utility scores are required for socio-economic evaluations,which can aid the distribution of national budgets.However,the standard health utility assessment scores for specific health conditions are largely unknown.AIM To summarize the health utility scores,including the EuroQOL 5-dimensions 5-levels(EQ-5D-5L),EuroQol-visual analogue scale,short from-36(SF-36),RAND-36,and Health Utilities Index(HUI)-Mark2/Mark3 scores,for the normal population and chronic liver disease patients.METHODS A systematic literature search of PubMed and MEDLINE,including the Cochrane Library,was performed.Meta-analysis was performed using the RevMan software.Multiple means and standard deviations were combined using the StatsToDo online web program.RESULTS The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C.HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients.CONCLUSION The EQ-5D-5L is the most popular questionnaire for health utility assessments.Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.
基金Supported by the Research Grants, No. NSC91-3112-B-002-009No. NSC92-3112-B-002-027,No. NSC93-3112-B-002-007from the National Science Council, No. NHRI-CN-CA9201S(92A084, and 93A059) from the National Health Research Institutes,and No. NTUH 93-N012 No. NTUH 94S155 from National Taiwan University Hospital, Taiwan, China
文摘AIM： A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue （MALT） lymphomas remain Helicobacter pylori （ H pylori）-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori- spedfic intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 （B7.2） and the infiltration of CD56 （＋） natural killer （NK） cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT iymphoma.METHODS： Lymphoma biopsies from 26 patients who had participated in a prospective study of Hpylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less alter H pylori eradication were dassified as H pylori-dependent; others were dassified as H pylori-dependent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS： There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 （68.8%） of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases （P = 0.001）.H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 （＋） NK cells than H pylori-independent cases （2.8±1.4% vs 1.1±0.8%, P = 0.003）. CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 （＋） NK cells compared to CD86-negative cases （2.9±1.1% vs 1.4±1.3%; P= 0.005）.CONCLUSION： These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with Hpylori-dependent state of early-stage high-grade
文摘Rationale:The mechanism of sudden cardiac death in COVID-19 can be multifactorial.Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some cases.Cytokine storm syndrome and idiosyncratic reaction with mesalazine use may lead to sudden cardiac death in COVID-19.Use of immunosuppressants in hospitalized COVID-19 patients should be continued with caution,especially in patients with inflammatory bowel disease.Patient’s concern:A 75-year-old man who was tested positive for SARS-CoV-2 was admitted with a history of shortness of breath for the last two days.He was a known case of Crohn’s disease treated with mesalazine.Diagnosis:COVID-19 pneumonia with underlying Crohn’s disease leading to sudden cardiac death.Intervention:Remdesivir,antibiotics,steroids,low molecular weight heparin,tablet zinc,tab vitamin C,and other supportive treatment were started.Because of increased inflammatory markers,itolizumab was given to the patient on the 2nd day.Outcome:On the 5th day of the intensive care unit,the patient complained of sudden chest pain with respiratory distress leading to bradycardia and asystole and could not be resuscitated.Lessons:Causes for sudden cardiac death in COVID-19 pneumonia patients with Crohn’s disease is multifactorial.Although mesalazine may be a safe and effective drug in the management of inflammatory bowel disease,it can induce sytokine strom syndrome and idiosyncratic reactions that could be one of the reasons of sudden cardic death.Therefore,we should be aware of its serious and potentially life-threatening complications,especially in COVID-19 infected patients.
基金supported by the Science and Technology Project in Guangzhou(No.201904010482)the National Natural Science Foundation of China(Nos.81570064,81870068,and 82070063).
文摘Background:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis,partially by activating lung fibroblasts.However,how macrophages communicate with lung fibroblasts is largely unexplored.Exosomes can mediate intercellular communication,whereas its role in lung fibrogenesis is unclear.Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo,bleomycin(BLM)-induced lung fibrosis model was established and macrophages infiltration was examined.The effects of GW4869,an exosomes inhibitor,on lung fibrosis were assessed.Moreover,macrophage exosomes were injected into mice to observe its pro-fibrotic effects.In vitro,exosomes derived from angiotensin Ⅱ(Ang Ⅱ)-stimulated macrophages were collected.Then,lung fibroblasts were treated with the exosomes.Twenty-four hours later,protein levels ofα-collagen I,angiotensin Ⅱ type 1 receptor(AT1R),transforming growth factor-β(TGF-β),and phospho-Smad2/3(p-Smad2/3)in lung fibroblasts were examined.The Student's t test or analysis of variance were used for statistical analysis.Results:In vivo,BLM-treated mice showed enhanced infiltration of macrophages,increased fibrotic alterations,and higher levels of Ang Ⅱ and AT1R.GW4869 attenuated BLM-induced pulmonary fibrosis.Mice with exosomes injection showed fibrotic features with higher levels of Ang Ⅱ and AT1R,which was reversed by irbesartan.In vitro,we found that macrophages secreted a great number of exosomes.The exosomes were taken by fibroblasts and resulted in higher levels of AT1R(0.22±0.02 vs.0.07±0.02,t=8.66,P=0.001),TGF-β(0.54±0.05 vs.0.09±0.06,t=10.00,P<0.001),p-Smad2/3(0.58±0.06 vs.0.07±0.03,t=12.86,P<0.001)andα-collagen I(0.27±0.02 vs.0.16±0.01,t=7.01,P=0.002),and increased Ang Ⅱ secretion(62.27±7.32 vs.9.56±1.68,t=12.16,P<0.001).Interestingly,Ang Ⅱ increased the number of macrophage exosomes,and the protein levels of Alix(1.45±0.15 vs.1.00±0.10,t=4.32,P=0.012),AT1R(4.05±0
基金the Flash Grant Call from the National Council for Scientific Research in Lebanon(CNRS-L)the American University of Beirut(AUB)titled:“Neurological Complications PostCoronavirus Disease(COVID-19)“(to FK)and“SARS-COV2 antibodies signature in exposed individuals to assess protection status”(to ES).
文摘As the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to spread globally,it became evident that the SARS-CoV-2 virus infects multiple organs including the brain.Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes.Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood,several theories have been suggested including direct and indirect pathways induced by the virus.One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route.Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells.Nevertheless,the indirect mechanisms,including blood-clotting abnormalities and prolonged activation of the immune system,can result in further tissue and organ damages seen during the course of the disease.This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.
基金funded by Beijing Science and Technology Commission Foundation[Z151100004015071]
文摘Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.
文摘Objective To explore the clinical and radiological features of severe acute respiratory syndrome (SARS).Methods Analysis of the clinical presentation, chest radiographs, course of disease and features of severe pneumonia in 45 SARS patients diagnosed at our hospital in Beijing between April 5 - 20, 2003. Also included is a summation of the clinical features of SARS.Results (1) SARS appears to have high infectivity; (2) the most common symptom is fever; (3) the count of leukocyte is normal or decreased; (4) most patients (35/45, 77.8%) had experienced a 24-hour fever prior to the abnormal chest X-ray changes which showed progression of pulmonary infiltrates within 48 hours in 71.1% (32/45) of the patients and, (5) the percentage of patients who developed severe pneumonia (24. 4%) is higher than those who developed typical pneumonia.Conclusion SARS is a disease with high infectivity and has its own clinical and radiological features. Early recognition, prompt isolation, and appropriate therapy are the key to combate this infection.
文摘Glycosylation of mucins mediated by N-acetylgalactosaminyltransferases(GALNTs)is closely related to respiratory diseases such as asthma and chronic obstructive pulmonary disease(COPD).In addition,long non-coding RNAs(LncRNAs)participate in physiological and pathological processes through various epigenetic mechanisms.In this study,we found that a novel LncRNA named NKILA combined with multiple mucins and GALNTs potentially by several bioinformatics methods,and we used quantitative real-time PCR(RT-qPCR)to detect the expressions of NKILA,MUC5AC,MUC5B,and GALNT2 mRNA in 50 cases of asthma samples and 19 cases of normal samples,whose results showed that the expression of NKILA was significantly decreased in asthmatic samples,negatively correlated with the severity of asthma and the expressions of MUC5AC and MUC5B,while GALNT2 was significantly increased in asthmatic tissues,and positively correlated with the severity of asthma and the expressions of MUC5AC and MUC5B.In vitro,we used transient transfection technology to overexpress or interfere with NKILA and GALNT2 and then detected the expressions of MUC5AC and MUC5B via RT-qPCR and Western blot,which demonstrated GALNT2 can promote the expressions of MUC5AC and MUC5B protein,while NKILA could inhibit this effect.Furthermore,co-immunoprecipitation results showed that GALNT2 could bind to MUC5AC and MUC5B protein.RNA immunoprecipitation and RNA pull-down experiments showed that NKILA could bind to GALNT2.These evidences suggested that there are correlations among the expression of NKILA,GALNT2,MUC5AC,and MUC5B proteins in asthmatic patients.Mechanically,we concluded that NKILA can suppress the O-linked glycosylation of MUC5AC and MUC5B proteins by binding to GALNT2 and inhibit the expression of MUC5AC and MUC5B proteins.Our researches provided a potential therapeutic target for AHR.
文摘Age determination is one of the most important factors for identification. Unfortunately, births are not recorded regularly in Sudan, especially in rural areas. However, identification of age is very important for a variety of reasons, including identifying legal and criminal responsibility, and for many other social events such as beginning a job, marriage, retirement and joining the army. The study aimed to find the reliability of using international methods to estimate bone age of people through hand bone radiograph in Sudanese people by studying the reliability of using hand bone age “the digital atlas of hand age” which depended on Greulich and Pyle (GP) and Tanner and Whitehouse (TW2/3) methods in Sudanese people in exact group of age, and to compare the hand and wrist bone development between Caucasian and Sudanese people. The study was conducted on 48 samples (26 males and 22 females) from the center of Sudan. The study was made by conventional X-Ray taken from Sudanese newborn babies to 2 and 3 years old for males and females respectively. Those images were taken mostly from the emergency and orthopedic outpatient departments. The ages were grouped in the same ways and periods used in the atlas. So the criteria were tested, and the outcomes were compared with international standards in the atlas of hand bone age. There is evidence that skeletal maturation may vary between difference ethnic and socioeconomic groups of children or among children living in various geographical locations. It is found that there is reliability and applicability of using the atlas in Sudanese people with considering that there might be mild variations between Sudanese and Caucasian people’s hand and wrist bone development in which Caucasian people bone growth was earlier than the Sudanese people bones about 1 - 2 months.
