Background: Falls in the elderly are a global public health problem with serious medical and socio-economic consequences, especially in low and middle-income countries. The aim of this study was to describe the charac...Background: Falls in the elderly are a global public health problem with serious medical and socio-economic consequences, especially in low and middle-income countries. The aim of this study was to describe the characteristics of falls among the elderly in trauma units in Senegal. Materials and Methods: This was a descriptive, prospective study from April 20, 2022 to October 30, 2022 among people aged at least 60 and admitted to the surgical emergency department of Idrissa Pouye Hospital in Dakar following a fall. Socio-demographic, clinical, therapeutic and evolutionary characteristics were collected and analyzed using Sphinx Plus 2 and Excel 2019 for Windows software. Results: Out of 730 elderly people seen during this period, 100 met the criteria, representing a prevalence of 13.69%. The average consultation time was 3.25 +/? 4 days. The average age was 73 +/? 8.43 years, with women predominating (74%). Medical expenses were mainly covered by the family (73%). Most falls occurred during the day (68%), at home (82%), especially in the bedroom (30%), with stumbling (32%) as the main mechanism. The majority of patients (86%) spent less than 30 minutes on the floor. Predisposing factors were dominated by visual disorders (56%) and precipitating factors were mainly environmental (62%). Geriatric syndromes were dominated by frailty (22%). Complications were dominated by fractures (86%), and almost half (47%) had lost their autonomy for post-fall Activities Daily Living (ADL). Prescription medication was almost systematic (98%), dominated by analgesics (98%). Surgery was indicated in 58% of patients. The average waiting time for surgery was 25.36 +/? 19 days. A death rate of 1% was recorded in the emergency department. Conclusion: Falls in the elderly are a frequent occurrence in traumatological emergencies, with etiological factors that are often multiple and interrelated, leading to significant morbidity. Raising awareness among people at risk and setting up an orthogeriatric service would help prevent falls and optimize care in the short and long term.展开更多
Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronar...Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.展开更多
BACKGROUND Frailty is a common condition in elderly patients who receive percutaneous coronary intervention(PCI).However,how frailty affects clinical outcomes in this group is unclear.AIM To assess the link between fr...BACKGROUND Frailty is a common condition in elderly patients who receive percutaneous coronary intervention(PCI).However,how frailty affects clinical outcomes in this group is unclear.AIM To assess the link between frailty and the outcomes,such as in-hospital complic-ations,post-procedural complications,and mortality,in elderly patients post-PCI.METHODS The PubMed/MEDLINE,EMBASE,Cochrane Library,and Web of Science databases were screened for publications up to August 2023.The primary outcomes assessed were in-hospital and all-cause mortality,major adverse cardiovascular events(MACEs),and major bleeding.The Newcastle-Ottawa Scale was used for quality assessment.RESULTS Twenty-one studies with 739693 elderly patients undergoing PCI were included.Frailty was consistently associated with adverse outcomes.Frail patients had significantly higher risks of in-hospital mortality[risk ratio:3.45,95%confidence interval(95%CI):1.90-6.25],all-cause mortality[hazard ratio(HR):2.08,95%CI:1.78-2.43],MACEs(HR:2.92,95%CI:1.85-4.60),and major bleeding(HR:4.60,95%CI:2.89-7.32)compared to non-frail patients.CONCLUSION Frailty is a pivotal determinant in the prediction of risk of mortality,development of MACEs,and major bleeding in elderly individuals undergoing percutaneous coronary intervention.展开更多
BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-su...BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-surgery.Consequently,cardiac rehabilitation holds immense importance in mitigating these complications.AIM To evaluate the effect of individualized cardiac rehabilitation on blood pressure variability(BPV)and baroreflex sensitivity(BRS)in elderly patients with myocardial infarction.METHODS A cohort of 74 elderly patients diagnosed with myocardial infarction and admitted to our hospital between January 2021 and January 2022 were subjected to random selection.Subsequently,all patients were divided into two groups,namely the research group(n=37)and the control group(n=37),utilizing the number table method.The control group received conventional drug treatment and nursing guidance intervention,while the study group underwent individualized cardiac rehabilitation in addition to the interventions received by the control group.All patients were continuously intervened for 12 wk,and the BPV of these two groups in the 1st wk(T0),the 4th wk(T1)and the 12th wk(T2)were compared,BRS,changes in cardiopulmonary function measures,and adverse cardiovascular events.RESULTS Of 24 h diastolic BPV,24 h systolic BPV,carbon dioxide ventilation equivalent slope of the research group were lower than those of the control group at T1 and T2,BRS,peak heart rate and systolic blood pressure product,1 min heart rate recovery were higher than those of the control group,and the incidence of adverse events in the research group was lower than that of the control group,the difference was statistically significant(P<0.05).CONCLUSION In this study,we found that after individualized cardiac rehabilitation in elderly patients with myocardial infarction,BPV and BRS can be effectively improved,cardiac function is significantly enhanced,and a better prognosis is obtained.展开更多
BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)fo...BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.展开更多
Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recr...Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.展开更多
Objectives Quality of life(QoL) is a priority outcome in older adults suffering from cardiovascular diseases. Frailty and poor nutritional status may affect the QoL through mobility disorders and exhaustion. The objec...Objectives Quality of life(QoL) is a priority outcome in older adults suffering from cardiovascular diseases. Frailty and poor nutritional status may affect the QoL through mobility disorders and exhaustion. The objective of this study was to determine if physical frailty and nutritional status were associated with QoL, in older cardiology patients. Methods Cross sectional, observational study conducted in a cardiology department from a university hospital. Participants(n = 100) were aged 70 and older. Collected data included age, sex, cardiac diseases, New York Heart Association(NYHA) classification, comorbidities(Charlson Index) and disability. A Short Physical Performance Battery(SPPB), including walking speed assessment was performed;handgrip strength were measured as well as Fried’s frailty phenotype. Nutritional status was assessed using the Mini Nutritional Assessment(MNA) and Body Mass Index(BMI), inflammation by C-reactive protein(CRP). QoL was assessed using the EORTC–QLQ questionnaire. Univariate and multivariate analyses were performed to study the associations between all recorded parameters and QoL. Results In participants(mean age: 79.3 ± 6.7 years;male: 59%), Charlson index, arrhythmia, heart failure, NYHA class III-IV, MNA, disability, walking speed, SPPB score, frailty and CRP were significantly associated with QoL in univariate analysis. Multivariate analysis showed that NYHA class III-IV(P < 0.001), lower MNA score(P = 0.03), frailty(P < 0.0001), and higher CRP(P < 0.001) were independently associated with decreased QoL. Conclusions Frailty, nutritional status and inflammation were independently associated with poor QoL. Further studies are needed to assess the efficacy of nutritional and physical interventions on QoL in this population.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
Ischemic stroke is one of the most common causes of mortality and disability worldwide.However,treatment efficacy and the progress of research remain unsatisfactory.As the critical support system and essential compone...Ischemic stroke is one of the most common causes of mortality and disability worldwide.However,treatment efficacy and the progress of research remain unsatisfactory.As the critical support system and essential components in neurovascular units,glial cells and blood vessels(including the bloodbrain barrier)together maintain an optimal microenvironment for neuronal function.They provide nutrients,regulate neuronal excitability,and prevent harmful substances from entering brain tissue.The highly dynamic networks of this support system play an essential role in ischemic stroke through processes including brain homeostasis,supporting neuronal function,and reacting to injuries.However,most studies have focused on postmortem animals,which inevitably lack critical information about the dynamic changes that occur after ischemic stroke.Therefore,a high-precision technique for research in living animals is urgently needed.Two-photon fluorescence laser-scanning microscopy is a powerful imaging technique that can facilitate live imaging at high spatiotemporal resolutions.Twophoton fluorescence laser-scanning microscopy can provide images of the whole-cortex vascular 3D structure,information on multicellular component interactions,and provide images of structure and function in the cranial window.This technique shifts the existing research paradigm from static to dynamic,from flat to stereoscopic,and from single-cell function to multicellular intercommunication,thus providing direct and reliable evidence to identify the pathophysiological mechanisms following ischemic stroke in an intact brain.In this review,we discuss exciting findings from research on the support system after ischemic stroke using two-photon fluorescence laser-scanning microscopy,highlighting the importance of dynamic observations of cellular behavior and interactions in the networks of the brain’s support systems.We show the excellent application prospects and advantages of two-photon fluorescence laser-scanning microscopy and predict future research developments and directions in the study of ischemic stroke.展开更多
Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reducta...Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood.The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice.We asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative stress.We also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and proteins.To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes.We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in vitro.Therefore,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.展开更多
BACKGROUND Recurrence is the major challenge facing endoscopic submucosal dissection(ESD)-based treatment therapies for early gastric cancer(EGC).Urgent development of simple and easy surveillance approaches will enha...BACKGROUND Recurrence is the major challenge facing endoscopic submucosal dissection(ESD)-based treatment therapies for early gastric cancer(EGC).Urgent development of simple and easy surveillance approaches will enhance clinical treatment of the disease.AIM To explore the role of computed tomography(CT)recurrence in evaluating EGC after ESD treatment.METHODS We retrospectively recruited patients from our endoscopy department,between January 2002 and December 2015,and analyzed their basic characteristics,including symptoms,CT results,and results of endoscopy with biopsy,among others.RESULTS Among a total of 2150 patients EGC patients surveyed,1362 met our inclusion and exclusion criteria and were therefore enrolled in our study.The cohort’s sensitivity of CT for recurrent GC and specificity were 44.22%and 43.86%,respectively,with negative and positive predictive values of 40.15%(275/685)and 48.01%(325/677),respectively.The area under the curve of arterial and venous CT values for recurrent EGC were 0.545,and 0.604,respectively.Receiver operating characteristic curve revealed no statistically significant differences between arterial and venous CT values for recurrent EGC.CONCLUSION Enhanced CT has superior diagnostic efficacy,but less accuracy,compared to gold standard techniques in patients with recurrent EGC.展开更多
OBJECTIVE To determine the role of ascending aorta dilatation in the relationship between pulse pressure(PP)and left ventricular(LV)hypertrophy.METHODS A total of 1556 Chinese elderly hypertensive patients were retros...OBJECTIVE To determine the role of ascending aorta dilatation in the relationship between pulse pressure(PP)and left ventricular(LV)hypertrophy.METHODS A total of 1556 Chinese elderly hypertensive patients were retrospectively studied.Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements.In addition,brachial blood pressure was measured,and total arterial compliance,systemic vascular resistance,arterial elastance,and end-systolic LV elastance were calculated.The participants were divided into four groups according to the status of ascending aortic diameter and PP.RESULTS LV mass index increased in succession in the four groups,i.e.,the group with the normal aorta and lower PP,with the normal aorta and higher PP,with aortic dilatation and lower PP,and with aortic dilatation and higher PP(Ptrend<0.001).Total arterial compliance−1,arterial elastance,and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation,regardless of PP being lower or higher(P<0.01).Compared to the group with the normal aorta and lower PP,individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy,and higher PP further exacerbated this risk[aortic dilatation with lower PP(OR=1.75,95%CI:1.01–3.04)and aortic dilatation with higher PP(OR=3.42,95%CI:2.03–5.77)].In the relation between PP and LV mass index(β=0.095,P<0.001),-41.3%of the total effect was attributable to mediation by ascending aortic diameter(P<0.0001).CONCLUSIONS In Chinese elderly patients with hypertension,ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.展开更多
Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4...Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4 per group):in control group,rats received no treatment;in sham group,rats underwent a sham operation;in SDN group,rats underwent SDN with half of the dorsal penile nerve severed.The mating test was performed,and the intracavernous pressure(ICP)assessed six weeks after the surgical treatment.Results At postoperative six weeks,the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups(P>0.05),while the ejaculation latency(EL)was significantly longer and ejaculation frequency(EF)lower in the SDN group than in the control and sham groups(P<0.05).There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure(MAP)among the three groups(P>0.05).Conclusion SDN does not adversely affect the erectile function and sexual desire of rats,and at the same time it can reduce EL and EF,providing an application basis for SDN in the clinical treatment of premature ejaculation.展开更多
Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calciu...Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells.The calcium signal is in connection with a series of processes critical in the tumorigenesis.Here,we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells.Mechanistically,calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase(FAK),protein kinase B,and p38 mitogen-activated protein kinase.The inhibitor of FAK or Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ)reversed the Ca2+-induced effects on HepG2 cells,including cell proliferation and migration,epithelial-mesenchymal transition protein expression levels,and phosphorylation levels of FAK and protein kinase B.Moreover,calcium ions decreased HepG2 cells'sensitivity to cisplatin.Furthermore,we found that the expression levels of FAK and CaMKⅡwere increased in hepatoblastoma.The group with high expression levels of FAK and CaMKⅡexhibited significantly lower ImmunoScore as well as CD8+T and NK cells.The expression of CaMKⅡwas positively correlated with that of PDCD1 and LAG3.Correspondingly,the expression of FAK was negatively correlated with that of TNFSF9,TNFRSF4,and TNFRSF18.Collectively,extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMKⅡand enhances cisplatin resistance.FAK and CaMKⅡshape immune cell infiltration and responses in tumor microenvironments,thereby serving as potential targets for hepatoblastoma.展开更多
Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against ...Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).展开更多
Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an i...Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.展开更多
Background: Proximity between older patients and their close relatives is essential during hospitalisation. During the first wave of the pandemic, the Danish Patient Safety Authority restricted no hospital visitors. A...Background: Proximity between older patients and their close relatives is essential during hospitalisation. During the first wave of the pandemic, the Danish Patient Safety Authority restricted no hospital visitors. Aim: To explore how older patients with COVID-19 and their close relatives experienced physical separation during hospitalization. Method: A qualitative study using semi-structured interviews and thematic analysis was employed. Findings: Six interviews were conducted: three patients with a mean age of 81 years and three close relatives—two daughters and one spouse. The patients felt boredom, loneliness, and a sense of imprisonment, yet they felt safe and satisfied. Isolation was known beforehand from the media. Close relatives emphasised that information, involvement, and collaboration with hospital staff were crucial. Conclusion: Although older patients with COVID-19 and their close relatives widely accept their situation during hospitalization, they experience negative consequences from social isolation.展开更多
BACKGROUND Western medicine is beneficial for the recovery of neurological function in patients with depression,but some patients experience side effects such as headaches,dizziness,nausea,gastrointestinal symptoms,in...BACKGROUND Western medicine is beneficial for the recovery of neurological function in patients with depression,but some patients experience side effects such as headaches,dizziness,nausea,gastrointestinal symptoms,insomnia,and cardiac dysfunction.In recent years,integrative medicine has achieved positive results in the treatment of various diseases.AIM To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors(SSRIs)in patients with herpes zoster complicated by depression.METHODS Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants.Among them,43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group,while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group.Both groups were treated for eight weeks.The degree of pain,effect of herpes zoster treatment,degree of improvement in depressive symptoms,serum neurotransmitter levels,sleep quality,and occurrence of adverse reactions were compared between the two groups.RESULTS We found that after eight weeks of drug treatment,the two treatment schemes achieved differing efficacy.In further comparison,we found that,compared with patients treated with SSRIs alone,patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment(P<0.05).Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain,better treatment efficacy for herpes zoster,better sleep quality,and a lower incidence of adverse reactions compared to those treated with SSRIs alone(P<0.05).All minor adverse reactions occurring during treatment were resolved after symptomatic treatment.CONCLUSION The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.展开更多
With increasing aging population,osteoporosis has emerged as a public health problem worldwide.Epidemiological data reveal that the prevalence of osteoporosis in cold regions is high,and low temperatures may crucially...With increasing aging population,osteoporosis has emerged as a public health problem worldwide.Epidemiological data reveal that the prevalence of osteoporosis in cold regions is high,and low temperatures may crucially affect bone mass.Recent studies have found that the transient receptor potential melastatin-8(TRPM8)channel,a cold-sensitive ion channel,can sense cold environment,and can be activated in cold environment.It may play an antagonistic role in low temperature-induced bone mass reduction.Mechanistically,this function may be ascribed to the activation of TRPM8 channel proteins in human bone marrow mesenchymal stem cells(hBM-MSCs),which causes osteoblast differentiation and mineralization in the bone.TRPM8 channel on the surface of brown adipocytes participates in the thermogenesis in brown adipose tissue(BAT)and the regulation of whole-body energy balance to maintain bone homeostasis.TRPM8 may be involved in bone remodeling throughout life.This paper reviews recent research on the possible antagonistic mechanism of TRPM8 in signaling pathways related to low temperature-induced bone mass loss and assesses the possibility of TRPM8 as a molecular target for the prevention and treatment of low temperature-induced osteoporosis in cold regions.展开更多
文摘Background: Falls in the elderly are a global public health problem with serious medical and socio-economic consequences, especially in low and middle-income countries. The aim of this study was to describe the characteristics of falls among the elderly in trauma units in Senegal. Materials and Methods: This was a descriptive, prospective study from April 20, 2022 to October 30, 2022 among people aged at least 60 and admitted to the surgical emergency department of Idrissa Pouye Hospital in Dakar following a fall. Socio-demographic, clinical, therapeutic and evolutionary characteristics were collected and analyzed using Sphinx Plus 2 and Excel 2019 for Windows software. Results: Out of 730 elderly people seen during this period, 100 met the criteria, representing a prevalence of 13.69%. The average consultation time was 3.25 +/? 4 days. The average age was 73 +/? 8.43 years, with women predominating (74%). Medical expenses were mainly covered by the family (73%). Most falls occurred during the day (68%), at home (82%), especially in the bedroom (30%), with stumbling (32%) as the main mechanism. The majority of patients (86%) spent less than 30 minutes on the floor. Predisposing factors were dominated by visual disorders (56%) and precipitating factors were mainly environmental (62%). Geriatric syndromes were dominated by frailty (22%). Complications were dominated by fractures (86%), and almost half (47%) had lost their autonomy for post-fall Activities Daily Living (ADL). Prescription medication was almost systematic (98%), dominated by analgesics (98%). Surgery was indicated in 58% of patients. The average waiting time for surgery was 25.36 +/? 19 days. A death rate of 1% was recorded in the emergency department. Conclusion: Falls in the elderly are a frequent occurrence in traumatological emergencies, with etiological factors that are often multiple and interrelated, leading to significant morbidity. Raising awareness among people at risk and setting up an orthogeriatric service would help prevent falls and optimize care in the short and long term.
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
基金supported by the National Natural Science Foundation of China(No.62172288).
文摘Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.
文摘BACKGROUND Frailty is a common condition in elderly patients who receive percutaneous coronary intervention(PCI).However,how frailty affects clinical outcomes in this group is unclear.AIM To assess the link between frailty and the outcomes,such as in-hospital complic-ations,post-procedural complications,and mortality,in elderly patients post-PCI.METHODS The PubMed/MEDLINE,EMBASE,Cochrane Library,and Web of Science databases were screened for publications up to August 2023.The primary outcomes assessed were in-hospital and all-cause mortality,major adverse cardiovascular events(MACEs),and major bleeding.The Newcastle-Ottawa Scale was used for quality assessment.RESULTS Twenty-one studies with 739693 elderly patients undergoing PCI were included.Frailty was consistently associated with adverse outcomes.Frail patients had significantly higher risks of in-hospital mortality[risk ratio:3.45,95%confidence interval(95%CI):1.90-6.25],all-cause mortality[hazard ratio(HR):2.08,95%CI:1.78-2.43],MACEs(HR:2.92,95%CI:1.85-4.60),and major bleeding(HR:4.60,95%CI:2.89-7.32)compared to non-frail patients.CONCLUSION Frailty is a pivotal determinant in the prediction of risk of mortality,development of MACEs,and major bleeding in elderly individuals undergoing percutaneous coronary intervention.
文摘BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-surgery.Consequently,cardiac rehabilitation holds immense importance in mitigating these complications.AIM To evaluate the effect of individualized cardiac rehabilitation on blood pressure variability(BPV)and baroreflex sensitivity(BRS)in elderly patients with myocardial infarction.METHODS A cohort of 74 elderly patients diagnosed with myocardial infarction and admitted to our hospital between January 2021 and January 2022 were subjected to random selection.Subsequently,all patients were divided into two groups,namely the research group(n=37)and the control group(n=37),utilizing the number table method.The control group received conventional drug treatment and nursing guidance intervention,while the study group underwent individualized cardiac rehabilitation in addition to the interventions received by the control group.All patients were continuously intervened for 12 wk,and the BPV of these two groups in the 1st wk(T0),the 4th wk(T1)and the 12th wk(T2)were compared,BRS,changes in cardiopulmonary function measures,and adverse cardiovascular events.RESULTS Of 24 h diastolic BPV,24 h systolic BPV,carbon dioxide ventilation equivalent slope of the research group were lower than those of the control group at T1 and T2,BRS,peak heart rate and systolic blood pressure product,1 min heart rate recovery were higher than those of the control group,and the incidence of adverse events in the research group was lower than that of the control group,the difference was statistically significant(P<0.05).CONCLUSION In this study,we found that after individualized cardiac rehabilitation in elderly patients with myocardial infarction,BPV and BRS can be effectively improved,cardiac function is significantly enhanced,and a better prognosis is obtained.
基金supported by National Natural Science Foundation of China(72274067)。
文摘BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.
基金supported by Youth Project of Basic Research Special Fund of Yunnan Province(no.202301AZ070001-146).
文摘Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.
文摘Objectives Quality of life(QoL) is a priority outcome in older adults suffering from cardiovascular diseases. Frailty and poor nutritional status may affect the QoL through mobility disorders and exhaustion. The objective of this study was to determine if physical frailty and nutritional status were associated with QoL, in older cardiology patients. Methods Cross sectional, observational study conducted in a cardiology department from a university hospital. Participants(n = 100) were aged 70 and older. Collected data included age, sex, cardiac diseases, New York Heart Association(NYHA) classification, comorbidities(Charlson Index) and disability. A Short Physical Performance Battery(SPPB), including walking speed assessment was performed;handgrip strength were measured as well as Fried’s frailty phenotype. Nutritional status was assessed using the Mini Nutritional Assessment(MNA) and Body Mass Index(BMI), inflammation by C-reactive protein(CRP). QoL was assessed using the EORTC–QLQ questionnaire. Univariate and multivariate analyses were performed to study the associations between all recorded parameters and QoL. Results In participants(mean age: 79.3 ± 6.7 years;male: 59%), Charlson index, arrhythmia, heart failure, NYHA class III-IV, MNA, disability, walking speed, SPPB score, frailty and CRP were significantly associated with QoL in univariate analysis. Multivariate analysis showed that NYHA class III-IV(P < 0.001), lower MNA score(P = 0.03), frailty(P < 0.0001), and higher CRP(P < 0.001) were independently associated with decreased QoL. Conclusions Frailty, nutritional status and inflammation were independently associated with poor QoL. Further studies are needed to assess the efficacy of nutritional and physical interventions on QoL in this population.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
基金supported by grants from the National Natural Science Foundation of China,Nos.92148206,82071330(to ZPT)82201745(to HN)the Natural Science Foundation of Hubei Province,China,Nos.2021BCA109(to ZPT)and 2021CFB067(to HN)。
文摘Ischemic stroke is one of the most common causes of mortality and disability worldwide.However,treatment efficacy and the progress of research remain unsatisfactory.As the critical support system and essential components in neurovascular units,glial cells and blood vessels(including the bloodbrain barrier)together maintain an optimal microenvironment for neuronal function.They provide nutrients,regulate neuronal excitability,and prevent harmful substances from entering brain tissue.The highly dynamic networks of this support system play an essential role in ischemic stroke through processes including brain homeostasis,supporting neuronal function,and reacting to injuries.However,most studies have focused on postmortem animals,which inevitably lack critical information about the dynamic changes that occur after ischemic stroke.Therefore,a high-precision technique for research in living animals is urgently needed.Two-photon fluorescence laser-scanning microscopy is a powerful imaging technique that can facilitate live imaging at high spatiotemporal resolutions.Twophoton fluorescence laser-scanning microscopy can provide images of the whole-cortex vascular 3D structure,information on multicellular component interactions,and provide images of structure and function in the cranial window.This technique shifts the existing research paradigm from static to dynamic,from flat to stereoscopic,and from single-cell function to multicellular intercommunication,thus providing direct and reliable evidence to identify the pathophysiological mechanisms following ischemic stroke in an intact brain.In this review,we discuss exciting findings from research on the support system after ischemic stroke using two-photon fluorescence laser-scanning microscopy,highlighting the importance of dynamic observations of cellular behavior and interactions in the networks of the brain’s support systems.We show the excellent application prospects and advantages of two-photon fluorescence laser-scanning microscopy and predict future research developments and directions in the study of ischemic stroke.
基金supported by grants from the National Natural Science Youth Foundation of China(Grant No.81501201)the National Natural Science Youth Foundation of Jiangsu Province(Grant No.BK20151032)Min Huang,and the project of Critical Care Medicine of the Key Clinical Specialty of Jiangsu Province.
文摘Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood.The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice.We asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative stress.We also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and proteins.To investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes.We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in vitro.Therefore,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
文摘BACKGROUND Recurrence is the major challenge facing endoscopic submucosal dissection(ESD)-based treatment therapies for early gastric cancer(EGC).Urgent development of simple and easy surveillance approaches will enhance clinical treatment of the disease.AIM To explore the role of computed tomography(CT)recurrence in evaluating EGC after ESD treatment.METHODS We retrospectively recruited patients from our endoscopy department,between January 2002 and December 2015,and analyzed their basic characteristics,including symptoms,CT results,and results of endoscopy with biopsy,among others.RESULTS Among a total of 2150 patients EGC patients surveyed,1362 met our inclusion and exclusion criteria and were therefore enrolled in our study.The cohort’s sensitivity of CT for recurrent GC and specificity were 44.22%and 43.86%,respectively,with negative and positive predictive values of 40.15%(275/685)and 48.01%(325/677),respectively.The area under the curve of arterial and venous CT values for recurrent EGC were 0.545,and 0.604,respectively.Receiver operating characteristic curve revealed no statistically significant differences between arterial and venous CT values for recurrent EGC.CONCLUSION Enhanced CT has superior diagnostic efficacy,but less accuracy,compared to gold standard techniques in patients with recurrent EGC.
基金the National Key Research and Development Program of China(No.2018 YFC2000301)。
文摘OBJECTIVE To determine the role of ascending aorta dilatation in the relationship between pulse pressure(PP)and left ventricular(LV)hypertrophy.METHODS A total of 1556 Chinese elderly hypertensive patients were retrospectively studied.Transthoracic echocardiography was used to obtain the aortic and cardiac structure measurements.In addition,brachial blood pressure was measured,and total arterial compliance,systemic vascular resistance,arterial elastance,and end-systolic LV elastance were calculated.The participants were divided into four groups according to the status of ascending aortic diameter and PP.RESULTS LV mass index increased in succession in the four groups,i.e.,the group with the normal aorta and lower PP,with the normal aorta and higher PP,with aortic dilatation and lower PP,and with aortic dilatation and higher PP(Ptrend<0.001).Total arterial compliance−1,arterial elastance,and end-systolic LV elastance were slightly higher in the individuals with normal aorta compared to those with aortic dilatation,regardless of PP being lower or higher(P<0.01).Compared to the group with the normal aorta and lower PP,individuals with aortic dilatation had a significantly increased multivariable adjusted risk of LV hypertrophy,and higher PP further exacerbated this risk[aortic dilatation with lower PP(OR=1.75,95%CI:1.01–3.04)and aortic dilatation with higher PP(OR=3.42,95%CI:2.03–5.77)].In the relation between PP and LV mass index(β=0.095,P<0.001),-41.3%of the total effect was attributable to mediation by ascending aortic diameter(P<0.0001).CONCLUSIONS In Chinese elderly patients with hypertension,ascending aorta dilatation could reduce the influence of elevated PP on LV hypertrophy.
基金study was supported by Wuhan Application Foundation Frontier Project(No.2019020701011428).
文摘Objective This study aimed to investigate the effect of penile selective dorsal neurectomy(SDN)on erectile function in rats.Methods Twelve adult male Sprague-Dawley rats(15 weeks old)were divided into three groups(n=4 per group):in control group,rats received no treatment;in sham group,rats underwent a sham operation;in SDN group,rats underwent SDN with half of the dorsal penile nerve severed.The mating test was performed,and the intracavernous pressure(ICP)assessed six weeks after the surgical treatment.Results At postoperative six weeks,the mating test revealed no significant difference in mounting latency and mounting frequency among the three groups(P>0.05),while the ejaculation latency(EL)was significantly longer and ejaculation frequency(EF)lower in the SDN group than in the control and sham groups(P<0.05).There were no significant differences in preoperative and postoperative ICP and ICP/mean arterial blood pressure(MAP)among the three groups(P>0.05).Conclusion SDN does not adversely affect the erectile function and sexual desire of rats,and at the same time it can reduce EL and EF,providing an application basis for SDN in the clinical treatment of premature ejaculation.
基金funded by the Jiangsu Medical Scientific Research Project of Jiangsu Health Commission(to Q.Y.)the 789 Outstanding Talent Program of SAHNMU(Grant No.789ZYRC 202070102 to Q.Y.)+1 种基金the Guangzhou Key Medical Discipline Construction Project(to Q.Y.)the National Natural Science Foundation of China(Grant Nos.81870409 and 81671543 to Q.Y.).
文摘Hepatoblastoma is the most frequent liver malignancy in children.HepG2 has been discovered as a hepatoblastoma-derived cell line and tends to form clumps in culture.Intriguingly,we observed that the addition of calcium ions reduced cell clumping and disassociated HepG2 cells.The calcium signal is in connection with a series of processes critical in the tumorigenesis.Here,we demonstrated that extracellular calcium ions induced morphological changes and enhanced the epithelial-mesenchymal transition in HepG2 cells.Mechanistically,calcium ions promoted HepG2 proliferation and migration by up-regulating the phosphorylation levels of focal adhesion kinase(FAK),protein kinase B,and p38 mitogen-activated protein kinase.The inhibitor of FAK or Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ)reversed the Ca2+-induced effects on HepG2 cells,including cell proliferation and migration,epithelial-mesenchymal transition protein expression levels,and phosphorylation levels of FAK and protein kinase B.Moreover,calcium ions decreased HepG2 cells'sensitivity to cisplatin.Furthermore,we found that the expression levels of FAK and CaMKⅡwere increased in hepatoblastoma.The group with high expression levels of FAK and CaMKⅡexhibited significantly lower ImmunoScore as well as CD8+T and NK cells.The expression of CaMKⅡwas positively correlated with that of PDCD1 and LAG3.Correspondingly,the expression of FAK was negatively correlated with that of TNFSF9,TNFRSF4,and TNFRSF18.Collectively,extracellular calcium accelerates HepG2 cell proliferation and migration via FAK and CaMKⅡand enhances cisplatin resistance.FAK and CaMKⅡshape immune cell infiltration and responses in tumor microenvironments,thereby serving as potential targets for hepatoblastoma.
基金supported by the Natural Science Foundation of Gansu Province[Grant Numbers 22JR5RA930,22JR5RA894]the Talent Project of Lanzhou Science and Technology Bureau[Grant Number 2022-3-44]+1 种基金the projects managed by the Administration of Traditional Chinese Medicine[Grant Number GZKG-2022-54]Intra Hospital Fund of the First Hospital of Lanzhou University[Grant Number ldyyyn2021101].
文摘Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).
基金suppor ted by the National Key Research and Development Program of China(2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)+2 种基金the National Natural Science Foundation of China(82074098,82003814)the CACMS Innovation Fund(CI2021A05101)the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-ND-010,ZZ15-ND-10 and ZZ14-FL-002)。
文摘Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.
文摘Background: Proximity between older patients and their close relatives is essential during hospitalisation. During the first wave of the pandemic, the Danish Patient Safety Authority restricted no hospital visitors. Aim: To explore how older patients with COVID-19 and their close relatives experienced physical separation during hospitalization. Method: A qualitative study using semi-structured interviews and thematic analysis was employed. Findings: Six interviews were conducted: three patients with a mean age of 81 years and three close relatives—two daughters and one spouse. The patients felt boredom, loneliness, and a sense of imprisonment, yet they felt safe and satisfied. Isolation was known beforehand from the media. Close relatives emphasised that information, involvement, and collaboration with hospital staff were crucial. Conclusion: Although older patients with COVID-19 and their close relatives widely accept their situation during hospitalization, they experience negative consequences from social isolation.
基金This study was reviewed and approved by Yantai Hospital of Traditional Chinese Medicine.
文摘BACKGROUND Western medicine is beneficial for the recovery of neurological function in patients with depression,but some patients experience side effects such as headaches,dizziness,nausea,gastrointestinal symptoms,insomnia,and cardiac dysfunction.In recent years,integrative medicine has achieved positive results in the treatment of various diseases.AIM To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors(SSRIs)in patients with herpes zoster complicated by depression.METHODS Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants.Among them,43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group,while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group.Both groups were treated for eight weeks.The degree of pain,effect of herpes zoster treatment,degree of improvement in depressive symptoms,serum neurotransmitter levels,sleep quality,and occurrence of adverse reactions were compared between the two groups.RESULTS We found that after eight weeks of drug treatment,the two treatment schemes achieved differing efficacy.In further comparison,we found that,compared with patients treated with SSRIs alone,patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment(P<0.05).Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain,better treatment efficacy for herpes zoster,better sleep quality,and a lower incidence of adverse reactions compared to those treated with SSRIs alone(P<0.05).All minor adverse reactions occurring during treatment were resolved after symptomatic treatment.CONCLUSION The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.
文摘With increasing aging population,osteoporosis has emerged as a public health problem worldwide.Epidemiological data reveal that the prevalence of osteoporosis in cold regions is high,and low temperatures may crucially affect bone mass.Recent studies have found that the transient receptor potential melastatin-8(TRPM8)channel,a cold-sensitive ion channel,can sense cold environment,and can be activated in cold environment.It may play an antagonistic role in low temperature-induced bone mass reduction.Mechanistically,this function may be ascribed to the activation of TRPM8 channel proteins in human bone marrow mesenchymal stem cells(hBM-MSCs),which causes osteoblast differentiation and mineralization in the bone.TRPM8 channel on the surface of brown adipocytes participates in the thermogenesis in brown adipose tissue(BAT)and the regulation of whole-body energy balance to maintain bone homeostasis.TRPM8 may be involved in bone remodeling throughout life.This paper reviews recent research on the possible antagonistic mechanism of TRPM8 in signaling pathways related to low temperature-induced bone mass loss and assesses the possibility of TRPM8 as a molecular target for the prevention and treatment of low temperature-induced osteoporosis in cold regions.
