Circular RNAs(circRNAs)are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends.A growing body of evidence suggests that circRNAs play important roles in physiology and patholo...Circular RNAs(circRNAs)are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends.A growing body of evidence suggests that circRNAs play important roles in physiology and pathology.In particular,accumulating data on circRNA functions in various central nervous system(CNS)diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders.In this review,we focus on the regulatory and functional roles of circRNAs in CNS diseases,highlighting their diagnostic and therapeutic potential,with the aim of providing new insights into CNS diseases.展开更多
The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs....The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs.Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear aetiology.Here,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse model.Notably,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS.Furthermore,we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP,leading to an increase in Gng4 expression via m^(6)A modifications.Our findings provide functional insight into the correlation between circHECW2 and m^(6)A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.展开更多
To the Editor:Acute respiratory distress syndrome(ARDS)ranks among the most prevalent conditions in the intensive care unit(ICU),with mortality rates soaring to 50%in cases progressing to moderate-to-severe ARDS.[1]A ...To the Editor:Acute respiratory distress syndrome(ARDS)ranks among the most prevalent conditions in the intensive care unit(ICU),with mortality rates soaring to 50%in cases progressing to moderate-to-severe ARDS.[1]A central pathogenic mechanism in lung injury involves pulmonary vascular endothelial damage,marked by heightened adhesion molecule expression,neutrophil infiltration,and increased endothelial permeability,culminating in pulmonary vascular endothelial dysfunction and compromised gas exchange.展开更多
Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its wid...Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its widespread application in clinical practice.Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT.In this study,we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.Methods This retrospective observational study was conducted using data from the Chinese database in intensive care(CDIC).Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021.We collected data during the first 7 days of ventilation to calculate various dead space estimates,including ventilatory ratio(VR),corrected minute ventilation(V_(Ecorr)),VD/VT(Harris–Benedict),VD/VT(Siddiki estimate),and VD/VT(Penn State estimate)longitudinally.A time-dependent Cox model was used to handle these time-varying estimates.Results A total of 392 patients(median age 66[interquartile range:55–77]years,median SOFA score 9[interquartile range:7–12])were finally included in our analysis,among whom 132(33.7%)patients died within 28 days of admission.VR(hazard ratio[HR]=1.04 per 0.1 increase,95%confidence interval[CI]:1.01 to 1.06;P=0.013),V_(Ecorr)(HR=1.08 per 1 increase,95%CI:1.04 to 1.12;P<0.001),VD/VT(Harris–Benedict)(HR=1.25 per 0.1 increase,95%CI:1.06 to 1.47;P=0.006),and VD/VT(Penn State estimate)(HR=1.22 per 0.1 increase,95%CI:1.04 to 1.44;P=0.017)remained significant after adjustment,while VD/VT(Siddiki estimate)(HR=1.10 per 0.1 increase,95%CI:1.00 to 1.20;P=0.058)did not.Given a large number of negative values,VD/VT(Siddiki estimate)and VD/VT(Penn State estimate)were not recommended as reliable substitutes.Long-term exposure to VR>1.3,V_(Ecorr)>7.53,and VD/VT(Harris–Benedict)>0.59 was independently associated with an increased risk of mortality in ARDS patients.These findings were validated in the fluid and catheter treatment trial(FACTT)database.Conclusions In cases where VD/VT cannot be measured directly,early time-varying estimates of VD/VT such as VR,,V_(Ecorr),and VD/VT(Harris–Benedict)can be considered for predicting mortality in ARDS patients,offering a rapid bedside application.展开更多
Background:To describe the current status of aerosol therapy during mechanical ventilation(MV)and the prac-tice,knowledge,and beliefs about aerosol therapy in physicians working in the intensive care unit(ICU)in China...Background:To describe the current status of aerosol therapy during mechanical ventilation(MV)and the prac-tice,knowledge,and beliefs about aerosol therapy in physicians working in the intensive care unit(ICU)in China.Methods:A physician self-administered questionnaire-based cross-sectional survey was carried out from January 2019 to July 2019.An electronic questionnaire was designed,and physicians who worked regularly in ICUs across several hospitals were contacted through WeChat.Answers to all questions and the general characteristics of physicians who answered the questionnaire were collected and analyzed.Results:A total of 2203 medical staffwho regularly worked in the ICUs completed this questionnaire(9.0%missing data);87.7%of the participants were doctors.Most respondents claimed that they often administered aerosolization therapy.Ultrasonic atomizer(50.7%)and jet nebulizer(48.6%)were the most commonly used atomization devices.Bronchodilators(65.8%)and steroids(66.3%)were the most frequently aerosolized drugs during MV.During nebulization,ventilator settings were never changed by 32.7%of respondents.Only 49.1%of respondents knew the appropriate place for a nebulizer.Further,62.7%of respondents using heated humidifiers reported turning them offduring nebulization.Specific knowledge about droplet size and nebulization yield was poor.Respondents from tertiary hospitals and those with higher technical title or work experience tended to have better accuracy than those from primary hospitals or with lower technical titles(P<0.050).Conclusions:Aerosol therapy was commonly used during MV,and the most frequent drugs were bronchodila-tors and steroids.Scientific knowledge about the optimal implementation of aerosol therapy during MV seemed deficient.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread throughout the world,which becomes a global public health emergency.Undernourishment prolongs its convalescence and has an adverse effect...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread throughout the world,which becomes a global public health emergency.Undernourishment prolongs its convalescence and has an adverse effect on its prognosis,especially in diabetic patients.The purpose of this study was to evaluate the prevalence and characteristics of undernourishment and to determine how it is related to the prognostic outcomes in the diabetic patients with coronavirus disease 2019(COVID-19).A retrospective,multicenter study was conducted in 85 diabetic COVID-19 patients from three hospitals in Hubei Province.All patients were assessed using the European Nutritional Risk Screening 2002(NRS-2002)and other nutritional assessments when admitted.Of them,35(41.18%)were at risk of malnutrition(NRS score≥3).Severe COVID-19 patients had a significantly lower level of serum albumin and prealbumin and higher NRS score than non-severe patients.Multivariate logistic regression analysis showed that serum prealbumin and NRS score increased the likelihood of progression into severe status(P<0.05).Meanwhile,single factor and multivariate analysis determined that grade of illness severity was an independent predictor for malnutrition.Furthermore,prealbumin and NRS score could well predict severe status for COVID-19 patients.The malnutrition group(NRS score≥3)had more severe illness than the normal nutritional(NRS score<3)group(P<0.001),and had a longer length of in-hospital stay and higher mortality.Malnutrition is highly prevalent among COVID-19 patients with diabetes.It is associated with severely ill status and poor prognosis.Evaluation of nutritional status should be strengthened,especially the indicators of NRS-2002 and the level of serum prealbumin.展开更多
Introduction Coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),is highly contagious[1]and has developed into a global pan-demic.Up to July 1,2022,COVID-...Introduction Coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),is highly contagious[1]and has developed into a global pan-demic.Up to July 1,2022,COVID-19 has affected>200 coun-tries and regions across the globe and caused 545,226,550 con-firmed cases and 6334,728 deaths,[2]seriously compromising human life,public properties.展开更多
Acute respiratory distress syndrome(ARDS)is a severe form of acute hypoxic respiratory failure caused by non-cardiogenic pulmonary edema.li since it was first described 50 years ago,the definition of ARDS has been rev...Acute respiratory distress syndrome(ARDS)is a severe form of acute hypoxic respiratory failure caused by non-cardiogenic pulmonary edema.li since it was first described 50 years ago,the definition of ARDS has been revised several times to match the needs of patients,clinicians,and investigators.展开更多
Introduction For critically ill patients with unstable hemodynamics,goal‑directed therapy for arterial blood pressure is needed with continuous daily bedside monitoring.The prevalence of hypertension in Chinese adults...Introduction For critically ill patients with unstable hemodynamics,goal‑directed therapy for arterial blood pressure is needed with continuous daily bedside monitoring.The prevalence of hypertension in Chinese adults is 25.2%,of which 1–2%of patients may experience a hypertensive emergency,with a mortality rate of 6.9%in the acute phase.The mortality and readmission rates within 90 days of onset are as high as 11%.[1]Furthermore,the mortality rate for patients who experience hypertensive emergencies can reach 50%within 12 months of the incident.[2]The incidence of perioperative hypertension in patients undergoing cardiac surgery is approximately 50%,with this figure dropping to 25%for non-cardiac surgery.Surgery may increase the incidence of perioperative cardio-cerebrovascular adverse events by 3–5%.[3]展开更多
Adriamycin(ADR),also known as doxorubicin,is an anthracycline anticancer drug and a chemotherapeutic drug commonly used in breast cancer treatments.1 However,breast cancer patients can gradually become tolerant to che...Adriamycin(ADR),also known as doxorubicin,is an anthracycline anticancer drug and a chemotherapeutic drug commonly used in breast cancer treatments.1 However,breast cancer patients can gradually become tolerant to chemotherapy.Therefore,improving the curative effect of ADR remains an urgent problem to be solved.Autophagy is a complex catabolic process;normal living cells break down damaged organelles or aggregated molecules and absorb energy to maintain homeostasis through autophagy.展开更多
Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsula...Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsulated metal-organic frameworks(MOFs) as co-reactants and terminal deoxynucleotidyl transferase(Td T)-mediated template-free branched polymerization, a dual signal-amplified electrochemiluminescent(ECL) biosensor was constructed to detect DNA adenine methylation(Dam) MTase. The employment of WO_(3-x) dots-encapsulated MOFs(i.e., NH_(2)-UIO66@WO_(3-x) ) was not only beneficial for biomolecule conjugation because of the abundant amino groups but also led to a 7-fold enhanced ECL response due to the increased loading of WO_(3-x). Moreover, Td T-mediated template-free branched polymerization promoted the capture of ECL emitters on the electrode surface, achieving 20-fold enhanced signal amplification. The presented ECL biosensor demonstrated a low detection limit of 2.4 × 10^(-4)U/m L, and displayed high reliability for the detection of Dam MTase in both spiked human serum and E. coli cell samples, and for the screening of potential inhibitors. This study opens a new avenue for designing a dual signal amplificationbased ECL bioassay for Dam MTase and screening inhibitors in the fields of clinical diagnosis and drug development.展开更多
Vitamin D binding protein(VDBP)serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target organs.VDBP plays a crucial part in the inflammatory reaction following...Vitamin D binding protein(VDBP)serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target organs.VDBP plays a crucial part in the inflammatory reaction following tissue damage and is engaged in actin degradation.Recent research has shed light on its potential role in various diseases,leading to a growing interest in understanding the implications of VDBP in psychiatric and neurological disorders.The purpose of this review was to provide a summary of the existing understanding regarding the involvement of VDBP in neurological and psychiatric disorders.By examining the intricate interplay between VDBP and these disorders,this review contributes to a deeper understanding of underlying mechanisms and potential therapeutic avenues.Insights gained from the study of VDBP could pave the way for novel strategies in the diagnosis,prognosis,and treatment of psychiatric and neurological disorders.展开更多
Background:Conventional pressure support ventilation(PSP)is triggered and cycled off by pneumatic signals such as flow.Patient-ventilator asynchrony is common during pressure support ventilation,thereby contributing t...Background:Conventional pressure support ventilation(PSP)is triggered and cycled off by pneumatic signals such as flow.Patient-ventilator asynchrony is common during pressure support ventilation,thereby contributing to an increased inspiratory effort.Using diaphragm electrical activity,neurally controlled pressure support(PSN)could hypothetically eliminate the asynchrony and reduce inspiratory effort.The purpose of this study was to compare the differences between PSN and PSP in terms of patient-ventilator synchrony,inspiratory effort,and breathing pattern.Methods:Eight post-operative patients without respiratory system comorbidity,eight patients with acute respiratory distress syndrome(ARDS)and obvious restrictive acute respiratory failure(ARF),and eight patients with chronic obstructive pulmonary disease(COPD)and mixed restrictive and obstructive ARF were enrolled.Patient-ventilator interactions were analyzed with macro asynchronies(ineffective,double,and auto triggering),micro asynchronies(inspiratory trigger delay,premature,and late cycling),and the total asynchrony index(AI).Inspiratory efforts for triggering and total inspiration were analyzed.Results:Total AI of PSN was consistently lower than that of PSP in COPD(3%vs.93%,P=0.012 for 100%support level;8%vs.104%,P=0.012 for 150%support level),ARDS(8%vs.29%,P=0.012 for 100%support level;16%vs.41%,P=0.017 for 150%support level),and post-operative patients(21%vs.35%,P=0.012 for 100%support level;15%vs.50%,P=0.017 for 150%support level).Improved support levels from 100%to 150%statistically increased total AI during PSP but not during PSN in patients with COPD or ARDS.Patients’inspiratory efforts for triggering and total inspiration were significantly lower during PSN than during PSP in patients with COPD or ARDS under both support levels(P<0.05).There was no difference in breathing patterns between PSN and PSP.Conclusions:PSN improves patient-ventilator synchrony and generates a respiratory pattern similar to PSP independently of any level of support in patients with different respiratory system mechanical properties.PSN,which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS,might be an alternative mode for PSP.Trial Registration:ClinicalTrials.gov,NCT01979627;https://clinicaltrials.gov/ct2/show/record/NCT01979627.展开更多
To the Editor:In sepsis,bacterial endotoxins play a central role by inducing a dysregulated and exaggerated release of inflammatory mediators and cytokines,often described as the“cytokine storm”or“cytokinemia.”[1]...To the Editor:In sepsis,bacterial endotoxins play a central role by inducing a dysregulated and exaggerated release of inflammatory mediators and cytokines,often described as the“cytokine storm”or“cytokinemia.”[1]Both endotoxins and cytokines have been implicated in the development of organ dysfunction,including acute kidney injury(AKI).[2]Removing circulating endotoxins and excess cytokines from the circulation restores chemotactic gradients,localizing the immune response to the principal site of infection and re-establishing a regulated immune response.[1,3]Therefore,using hemofilters with enhanced endotoxin and cytokine adsorptive properties may bring about additional therapeutic benefits compared with conventional continuous renal replacement therapy(CRRT)filters.展开更多
The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to...The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to serious side effects and significantly narrow the scope of their application.The self-assembly of intermediate filaments with arginine-glycine-aspartate(RGD)peptide(RGDIFP)was triggered by the hydrophobic cationic molecule 7-amino actinomycin D(7-AAD)to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment.The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method.This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes,ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA.It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential,but also potent antitumor therapeutic effects in vivo.The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.展开更多
Dear Editor,The first coronavirus disease 2019(COVID-19)outbreak was reported in Wuhan,Hubei,China.As one of the cities closest to Wuhan,Huangshi is considered a subcenter of the Wuhan metropolitan area.This study was...Dear Editor,The first coronavirus disease 2019(COVID-19)outbreak was reported in Wuhan,Hubei,China.As one of the cities closest to Wuhan,Huangshi is considered a subcenter of the Wuhan metropolitan area.This study was carried out to describe the characteristics of adult patients with confirmed COVID-19 in Huangshi.展开更多
Background:Pulmonary microvascular endothelial cells(PMVECs)were not complex,and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury(ALI)/acute respiratory distress syndrome(ARDS).P...Background:Pulmonary microvascular endothelial cells(PMVECs)were not complex,and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury(ALI)/acute respiratory distress syndrome(ARDS).Previous studies have demonstrated that hepatocyte growth factor(HGF),which was secreted by bone marrow mesenchymal stem cells,could decrease endothelial apoptosis.We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide(LPS)-induced endothelial barrier dysfunction and ALI mice.Methods:In our current study,we introduced LPS-induced PMEVCs with HGF treatment.To investigate the effects of mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3)pathway in endothelial oxidative stress and mitochondria-dependent apoptosis,mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were,respectively,used to inhibit mTOR/STAT3 signaling.Moreover,lentivirus vector-mediatedmTORC1(Raptor)andmTORC2(Rictor)gene knockdown modifications were introduced to evaluatemTORC1 andmTORC1 pathways.Calcium measurement,reactive oxygen species(ROS)production,mitochondrial membrane potential and protein,cell proliferation,apoptosis,and endothelial junction protein were detected to evaluate HGF effects.Moreover,we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscopein vivo.Results:Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake,which lead to increased mitochondrial membrane potential(JC-1 and mitochondria tracker green detection)and specific proteins(complex I),raised anti-apoptosis Messenger Ribonucleic Acid level(B-cell lymphoma 2 and Bcl-xL),and increased endothelial junction proteins(VE-cadherin and occludin).Reversely,mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells.Similarly,mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis.Inin vivo experiments of ALI mouse,HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.Conclusion:In all,these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level,mitochondria-dependent apoptosis,and endothelial junction protein in ARDS,contributing to the pulmonary endothelial survival and barrier integrity.展开更多
Coronavirus disease 2019(COVID-19)may rapidly worsen respiratory failure,thereby leading to death.COVID-19-induced respiratory failure exhibits some atypical characteristics,silent hypoxemia,and high lung compliance.S...Coronavirus disease 2019(COVID-19)may rapidly worsen respiratory failure,thereby leading to death.COVID-19-induced respiratory failure exhibits some atypical characteristics,silent hypoxemia,and high lung compliance.Some histopathological changes associated with COVID-19-induced respiratory failure differ from those of classic acute respiratory distress syndrome(ARDS).However,compared with classical ARDS,COVID-19-induced respi-ratory failure has a similar timing of onset,clinical syndromes,radiological profile,and mortality rate in the intensive care unit(ICU).Respiratory failure induced by COVID-19 is a type of ARDS and is currently underdiag-nosed.This condition stretches the definition of classic ARDS;therefore,an updated definition is warranted.展开更多
基金supported by grants from the Science and Technology Innovation 2030-Major Project of the Ministry of Science and Technology of China(No.2021ZD0202904 and No.2021ZD0202900)the National Natural Science Foundation of China(No.82230115 and No.82273914)+1 种基金the National Science Fund for Distinguished Young Scholars(No.82025033)the Jiangsu Provincial Key Laboratory of Critical Care Medicine(No.JSKLCCM-2022-02-008).
文摘Circular RNAs(circRNAs)are a class of regulatory non-coding RNAs characterized by the presence of covalently closed ends.A growing body of evidence suggests that circRNAs play important roles in physiology and pathology.In particular,accumulating data on circRNA functions in various central nervous system(CNS)diseases and their correlations indicate that circRNAs are critical contributors to the onset and development of brain disorders.In this review,we focus on the regulatory and functional roles of circRNAs in CNS diseases,highlighting their diagnostic and therapeutic potential,with the aim of providing new insights into CNS diseases.
基金This work was supported by grants from the Science and Technology Innovation 2030-Major Project of the Ministry of Science and Technology of China(2021ZD0202904/2021ZD0202900)the National Science Fund Distinguished Young Scholars(82025033,China)+4 种基金the National Natural Science Foundation of China(82230115,82273914,81903591,82372024,82003733)the Natural Science Foundation of Jiangsu Province(BK20200358,China)ZhiShan Scholar Program of Southeast University(2242022R40059 and 2242021R40023,China)the Jiangsu Provincial Key Laboratory of Critical Care Medicine(JSKLCCM-2022-02-008,China)the Open Project Program of the Key Laboratory of Developmental Genes and Human Diseases of the Ministry of Education(LDGHD202304,China).
文摘The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs.Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear aetiology.Here,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse model.Notably,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS.Furthermore,we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP,leading to an increase in Gng4 expression via m^(6)A modifications.Our findings provide functional insight into the correlation between circHECW2 and m^(6)A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.
基金supported by grants from Jiangsu Province’s Key Discipline/Laboratory of Medicine(No.ZDXKA2016025)Jiangsu Provincial Maternal and Child Health Research Project(No.F2021-05)Nanjing Medical Science and Technology Development Project(No.YKK20234).
文摘To the Editor:Acute respiratory distress syndrome(ARDS)ranks among the most prevalent conditions in the intensive care unit(ICU),with mortality rates soaring to 50%in cases progressing to moderate-to-severe ARDS.[1]A central pathogenic mechanism in lung injury involves pulmonary vascular endothelial damage,marked by heightened adhesion molecule expression,neutrophil infiltration,and increased endothelial permeability,culminating in pulmonary vascular endothelial dysfunction and compromised gas exchange.
基金supported by the Key Technologies Research and Development Program(Grant numbers:2022YFC2504400 and 2021YFC2500804)the Jiangsu Provincial Key Research and Development Program(Grant number:BE2022854).
文摘Background The dead space fraction(VD/VT)has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome(ARDS).However,its measurement relies on expired carbon dioxide,limiting its widespread application in clinical practice.Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT.In this study,we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation.Methods This retrospective observational study was conducted using data from the Chinese database in intensive care(CDIC).Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021.We collected data during the first 7 days of ventilation to calculate various dead space estimates,including ventilatory ratio(VR),corrected minute ventilation(V_(Ecorr)),VD/VT(Harris–Benedict),VD/VT(Siddiki estimate),and VD/VT(Penn State estimate)longitudinally.A time-dependent Cox model was used to handle these time-varying estimates.Results A total of 392 patients(median age 66[interquartile range:55–77]years,median SOFA score 9[interquartile range:7–12])were finally included in our analysis,among whom 132(33.7%)patients died within 28 days of admission.VR(hazard ratio[HR]=1.04 per 0.1 increase,95%confidence interval[CI]:1.01 to 1.06;P=0.013),V_(Ecorr)(HR=1.08 per 1 increase,95%CI:1.04 to 1.12;P<0.001),VD/VT(Harris–Benedict)(HR=1.25 per 0.1 increase,95%CI:1.06 to 1.47;P=0.006),and VD/VT(Penn State estimate)(HR=1.22 per 0.1 increase,95%CI:1.04 to 1.44;P=0.017)remained significant after adjustment,while VD/VT(Siddiki estimate)(HR=1.10 per 0.1 increase,95%CI:1.00 to 1.20;P=0.058)did not.Given a large number of negative values,VD/VT(Siddiki estimate)and VD/VT(Penn State estimate)were not recommended as reliable substitutes.Long-term exposure to VR>1.3,V_(Ecorr)>7.53,and VD/VT(Harris–Benedict)>0.59 was independently associated with an increased risk of mortality in ARDS patients.These findings were validated in the fluid and catheter treatment trial(FACTT)database.Conclusions In cases where VD/VT cannot be measured directly,early time-varying estimates of VD/VT such as VR,,V_(Ecorr),and VD/VT(Harris–Benedict)can be considered for predicting mortality in ARDS patients,offering a rapid bedside application.
基金This study was supported by the National Science and Tech-nology Major Project(Grant No.2020ZX09201015)the Clinical Science and Technology Specific Projects of Jiangsu Province(Grant Nos BE2018743,BE2019749)+3 种基金the National Natural Sci-ence Foundation of China(Grant Nos.81870066,81670074,81930058)the Natural Science Foundation of Jiangsu Province(Grant No.BK20171271)the Jiangsu Provincial Medical Youth Talent(Grant No.QNRC 2016807)the Third Level Tal-ents of the“333 High Level Talents Training Project”in the fifth phase in Jiangsu(Grant No.LGY2016051).
文摘Background:To describe the current status of aerosol therapy during mechanical ventilation(MV)and the prac-tice,knowledge,and beliefs about aerosol therapy in physicians working in the intensive care unit(ICU)in China.Methods:A physician self-administered questionnaire-based cross-sectional survey was carried out from January 2019 to July 2019.An electronic questionnaire was designed,and physicians who worked regularly in ICUs across several hospitals were contacted through WeChat.Answers to all questions and the general characteristics of physicians who answered the questionnaire were collected and analyzed.Results:A total of 2203 medical staffwho regularly worked in the ICUs completed this questionnaire(9.0%missing data);87.7%of the participants were doctors.Most respondents claimed that they often administered aerosolization therapy.Ultrasonic atomizer(50.7%)and jet nebulizer(48.6%)were the most commonly used atomization devices.Bronchodilators(65.8%)and steroids(66.3%)were the most frequently aerosolized drugs during MV.During nebulization,ventilator settings were never changed by 32.7%of respondents.Only 49.1%of respondents knew the appropriate place for a nebulizer.Further,62.7%of respondents using heated humidifiers reported turning them offduring nebulization.Specific knowledge about droplet size and nebulization yield was poor.Respondents from tertiary hospitals and those with higher technical title or work experience tended to have better accuracy than those from primary hospitals or with lower technical titles(P<0.050).Conclusions:Aerosol therapy was commonly used during MV,and the most frequent drugs were bronchodila-tors and steroids.Scientific knowledge about the optimal implementation of aerosol therapy during MV seemed deficient.
基金the National Natural Science Foundation of China(No.81970217 to WG)Science and Technology Development Foundation,Nanjing Medical University,China(No.NMUB2019074 to CZ)+2 种基金Natural Science Foundation for Colleges and Universities in Jiangsu Province(No.20KJB320010 to CZ)Science and Technology Development Foundation of Geriatric,Geriatrics Society of Jiangsu(No.JGS2019ZXYY06 to XL)National Key R&D Program of China(No.2020YFC2008505 to XL)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread throughout the world,which becomes a global public health emergency.Undernourishment prolongs its convalescence and has an adverse effect on its prognosis,especially in diabetic patients.The purpose of this study was to evaluate the prevalence and characteristics of undernourishment and to determine how it is related to the prognostic outcomes in the diabetic patients with coronavirus disease 2019(COVID-19).A retrospective,multicenter study was conducted in 85 diabetic COVID-19 patients from three hospitals in Hubei Province.All patients were assessed using the European Nutritional Risk Screening 2002(NRS-2002)and other nutritional assessments when admitted.Of them,35(41.18%)were at risk of malnutrition(NRS score≥3).Severe COVID-19 patients had a significantly lower level of serum albumin and prealbumin and higher NRS score than non-severe patients.Multivariate logistic regression analysis showed that serum prealbumin and NRS score increased the likelihood of progression into severe status(P<0.05).Meanwhile,single factor and multivariate analysis determined that grade of illness severity was an independent predictor for malnutrition.Furthermore,prealbumin and NRS score could well predict severe status for COVID-19 patients.The malnutrition group(NRS score≥3)had more severe illness than the normal nutritional(NRS score<3)group(P<0.001),and had a longer length of in-hospital stay and higher mortality.Malnutrition is highly prevalent among COVID-19 patients with diabetes.It is associated with severely ill status and poor prognosis.Evaluation of nutritional status should be strengthened,especially the indicators of NRS-2002 and the level of serum prealbumin.
基金supported by the Shanghai Science and Technology Commission(Grant No.20DZ2200500).
文摘Introduction Coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),is highly contagious[1]and has developed into a global pan-demic.Up to July 1,2022,COVID-19 has affected>200 coun-tries and regions across the globe and caused 545,226,550 con-firmed cases and 6334,728 deaths,[2]seriously compromising human life,public properties.
基金Key Research and Development Plan of Jiangsu Province(BE2020786 and BE2019749)Second Level Talents of the“333 High Level Talents Training Project”in the sixth phase in Jiangsu(LGY2022XXX).
文摘Acute respiratory distress syndrome(ARDS)is a severe form of acute hypoxic respiratory failure caused by non-cardiogenic pulmonary edema.li since it was first described 50 years ago,the definition of ARDS has been revised several times to match the needs of patients,clinicians,and investigators.
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Numbers:82172152,81873944,82241044,81971869,82172154).
文摘Introduction For critically ill patients with unstable hemodynamics,goal‑directed therapy for arterial blood pressure is needed with continuous daily bedside monitoring.The prevalence of hypertension in Chinese adults is 25.2%,of which 1–2%of patients may experience a hypertensive emergency,with a mortality rate of 6.9%in the acute phase.The mortality and readmission rates within 90 days of onset are as high as 11%.[1]Furthermore,the mortality rate for patients who experience hypertensive emergencies can reach 50%within 12 months of the incident.[2]The incidence of perioperative hypertension in patients undergoing cardiac surgery is approximately 50%,with this figure dropping to 25%for non-cardiac surgery.Surgery may increase the incidence of perioperative cardio-cerebrovascular adverse events by 3–5%.[3]
基金funded by the National Natural Science Foundation of China(No.81972478)the Fundamental Research Funds for the Central Universities(China)(No.2242020K40131)the Jiangsu Provincial Key Laboratory of Critical Care Medicine(China)(No.JSKLCCM-2022-02-013).
文摘Adriamycin(ADR),also known as doxorubicin,is an anthracycline anticancer drug and a chemotherapeutic drug commonly used in breast cancer treatments.1 However,breast cancer patients can gradually become tolerant to chemotherapy.Therefore,improving the curative effect of ADR remains an urgent problem to be solved.Autophagy is a complex catabolic process;normal living cells break down damaged organelles or aggregated molecules and absorb energy to maintain homeostasis through autophagy.
基金supported by the National Natural Science Foundation of China (Nos.22074015 and 22174014)。
文摘Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsulated metal-organic frameworks(MOFs) as co-reactants and terminal deoxynucleotidyl transferase(Td T)-mediated template-free branched polymerization, a dual signal-amplified electrochemiluminescent(ECL) biosensor was constructed to detect DNA adenine methylation(Dam) MTase. The employment of WO_(3-x) dots-encapsulated MOFs(i.e., NH_(2)-UIO66@WO_(3-x) ) was not only beneficial for biomolecule conjugation because of the abundant amino groups but also led to a 7-fold enhanced ECL response due to the increased loading of WO_(3-x). Moreover, Td T-mediated template-free branched polymerization promoted the capture of ECL emitters on the electrode surface, achieving 20-fold enhanced signal amplification. The presented ECL biosensor demonstrated a low detection limit of 2.4 × 10^(-4)U/m L, and displayed high reliability for the detection of Dam MTase in both spiked human serum and E. coli cell samples, and for the screening of potential inhibitors. This study opens a new avenue for designing a dual signal amplificationbased ECL bioassay for Dam MTase and screening inhibitors in the fields of clinical diagnosis and drug development.
基金the National Natural Science Key Foundation of China(No.82130042 to ZJ Zhang)the National Natural Science Foundation of China(No.82371532 to Y Kong).
文摘Vitamin D binding protein(VDBP)serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target organs.VDBP plays a crucial part in the inflammatory reaction following tissue damage and is engaged in actin degradation.Recent research has shed light on its potential role in various diseases,leading to a growing interest in understanding the implications of VDBP in psychiatric and neurological disorders.The purpose of this review was to provide a summary of the existing understanding regarding the involvement of VDBP in neurological and psychiatric disorders.By examining the intricate interplay between VDBP and these disorders,this review contributes to a deeper understanding of underlying mechanisms and potential therapeutic avenues.Insights gained from the study of VDBP could pave the way for novel strategies in the diagnosis,prognosis,and treatment of psychiatric and neurological disorders.
基金National Science and Technology Major Project(No.2020ZX09201015)Clinical Science and Technology Specific Projects of Jiangsu Province(Nos.BE2018743,BE2019749)+3 种基金National Natural Science Foundation of China(Nos.81870066,81670074,81930058)Natural Science Foundation of Jiangsu Province(No.BK20171271)Jiangsu Provincial Medical Youth Talent(No.QNRC 2016807)Third Level Talents of the"333 High Level Talents Training Project"in the fifth phase in Jiangsu(No.LGY2016051)。
文摘Background:Conventional pressure support ventilation(PSP)is triggered and cycled off by pneumatic signals such as flow.Patient-ventilator asynchrony is common during pressure support ventilation,thereby contributing to an increased inspiratory effort.Using diaphragm electrical activity,neurally controlled pressure support(PSN)could hypothetically eliminate the asynchrony and reduce inspiratory effort.The purpose of this study was to compare the differences between PSN and PSP in terms of patient-ventilator synchrony,inspiratory effort,and breathing pattern.Methods:Eight post-operative patients without respiratory system comorbidity,eight patients with acute respiratory distress syndrome(ARDS)and obvious restrictive acute respiratory failure(ARF),and eight patients with chronic obstructive pulmonary disease(COPD)and mixed restrictive and obstructive ARF were enrolled.Patient-ventilator interactions were analyzed with macro asynchronies(ineffective,double,and auto triggering),micro asynchronies(inspiratory trigger delay,premature,and late cycling),and the total asynchrony index(AI).Inspiratory efforts for triggering and total inspiration were analyzed.Results:Total AI of PSN was consistently lower than that of PSP in COPD(3%vs.93%,P=0.012 for 100%support level;8%vs.104%,P=0.012 for 150%support level),ARDS(8%vs.29%,P=0.012 for 100%support level;16%vs.41%,P=0.017 for 150%support level),and post-operative patients(21%vs.35%,P=0.012 for 100%support level;15%vs.50%,P=0.017 for 150%support level).Improved support levels from 100%to 150%statistically increased total AI during PSP but not during PSN in patients with COPD or ARDS.Patients’inspiratory efforts for triggering and total inspiration were significantly lower during PSN than during PSP in patients with COPD or ARDS under both support levels(P<0.05).There was no difference in breathing patterns between PSN and PSP.Conclusions:PSN improves patient-ventilator synchrony and generates a respiratory pattern similar to PSP independently of any level of support in patients with different respiratory system mechanical properties.PSN,which reduces the trigger and total patient’s inspiratory effort in patients with COPD or ARDS,might be an alternative mode for PSP.Trial Registration:ClinicalTrials.gov,NCT01979627;https://clinicaltrials.gov/ct2/show/record/NCT01979627.
文摘To the Editor:In sepsis,bacterial endotoxins play a central role by inducing a dysregulated and exaggerated release of inflammatory mediators and cytokines,often described as the“cytokine storm”or“cytokinemia.”[1]Both endotoxins and cytokines have been implicated in the development of organ dysfunction,including acute kidney injury(AKI).[2]Removing circulating endotoxins and excess cytokines from the circulation restores chemotactic gradients,localizing the immune response to the principal site of infection and re-establishing a regulated immune response.[1,3]Therefore,using hemofilters with enhanced endotoxin and cytokine adsorptive properties may bring about additional therapeutic benefits compared with conventional continuous renal replacement therapy(CRRT)filters.
基金supported by the National Natural Science Foundation of China(No.81603016,81773624,81900453)the Natural Science Foundation of Jiangsu Province(No.BK20160706,BE2017746,China)the National Science and Technology Major Project(2018ZX09301026-005,2020ZX09201015,China)。
文摘The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to serious side effects and significantly narrow the scope of their application.The self-assembly of intermediate filaments with arginine-glycine-aspartate(RGD)peptide(RGDIFP)was triggered by the hydrophobic cationic molecule 7-amino actinomycin D(7-AAD)to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment.The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method.This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes,ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA.It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential,but also potent antitumor therapeutic effects in vivo.The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.
基金The study was supported by the National Natural Science Foundation of China(Grant No.81971812)the Natural Science Foundation of Jiangsu Province(Grant No.SBK2019022548)the Science Foundation of the Commission of Health of Jiangsu Province(Grant No.ZDB2020009).
文摘Dear Editor,The first coronavirus disease 2019(COVID-19)outbreak was reported in Wuhan,Hubei,China.As one of the cities closest to Wuhan,Huangshi is considered a subcenter of the Wuhan metropolitan area.This study was carried out to describe the characteristics of adult patients with confirmed COVID-19 in Huangshi.
基金the National Natural Science Foundation of China(Nos.81671892,81971888,81971812,82102300)the Jiangsu Natural Science Foundation(Nos.BK20200367,BK20161433,BK20191264,BK20200356)+2 种基金the Jiangsu Province Medical Key Talent(No.ZDRCA2016082)the Jiangsu Province Key Medical Discipline(laboratory)(No.ZDXKA2016025)the Jiangsu Entrepreneurship and Innovation Doctors。
文摘Background:Pulmonary microvascular endothelial cells(PMVECs)were not complex,and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury(ALI)/acute respiratory distress syndrome(ARDS).Previous studies have demonstrated that hepatocyte growth factor(HGF),which was secreted by bone marrow mesenchymal stem cells,could decrease endothelial apoptosis.We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide(LPS)-induced endothelial barrier dysfunction and ALI mice.Methods:In our current study,we introduced LPS-induced PMEVCs with HGF treatment.To investigate the effects of mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3)pathway in endothelial oxidative stress and mitochondria-dependent apoptosis,mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were,respectively,used to inhibit mTOR/STAT3 signaling.Moreover,lentivirus vector-mediatedmTORC1(Raptor)andmTORC2(Rictor)gene knockdown modifications were introduced to evaluatemTORC1 andmTORC1 pathways.Calcium measurement,reactive oxygen species(ROS)production,mitochondrial membrane potential and protein,cell proliferation,apoptosis,and endothelial junction protein were detected to evaluate HGF effects.Moreover,we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscopein vivo.Results:Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake,which lead to increased mitochondrial membrane potential(JC-1 and mitochondria tracker green detection)and specific proteins(complex I),raised anti-apoptosis Messenger Ribonucleic Acid level(B-cell lymphoma 2 and Bcl-xL),and increased endothelial junction proteins(VE-cadherin and occludin).Reversely,mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells.Similarly,mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis.Inin vivo experiments of ALI mouse,HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.Conclusion:In all,these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level,mitochondria-dependent apoptosis,and endothelial junction protein in ARDS,contributing to the pulmonary endothelial survival and barrier integrity.
基金the National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China(Grant Number:2017ZX10103004)the National Natural Science Foundation of China(Grant Numbers:81671892,81971888)+3 种基金the Jiangsu Province’s Key Discipline/Laboratory of Medicine(Grant Number:ZDXKA2016025)the Jiangsu Province’s Key Provincial Talents Program(Grant Number:ZDRCA2016082)the Natural Science Foundation of Jiangsu Province(Grant Number:BK20161433)and the Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant Number:KYCX180181).
文摘Coronavirus disease 2019(COVID-19)may rapidly worsen respiratory failure,thereby leading to death.COVID-19-induced respiratory failure exhibits some atypical characteristics,silent hypoxemia,and high lung compliance.Some histopathological changes associated with COVID-19-induced respiratory failure differ from those of classic acute respiratory distress syndrome(ARDS).However,compared with classical ARDS,COVID-19-induced respi-ratory failure has a similar timing of onset,clinical syndromes,radiological profile,and mortality rate in the intensive care unit(ICU).Respiratory failure induced by COVID-19 is a type of ARDS and is currently underdiag-nosed.This condition stretches the definition of classic ARDS;therefore,an updated definition is warranted.
