BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine...BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine kinase-myocardial band isoenzyme(CK-MB)combined with different cardiac troponin(c Tn)assays in AMI diagnosis.METHODS:This multicenter,observational study included 3,706 patients with acute chest pain from September 1,2015,to September 30,2017.We classified the participants into three groups according to the c Tn assays:the point-of-care c Tn(POC-c Tn)group,the contemporary c Tn(c-c Tn)group,and hs-c Tn group.The diagnostic value was quantified using sensitivity and the area under the curve(AUC).RESULTS:Compared to the single POC-c Tn/c-c Tn assays,combining CK-MB and POC-c Tn/c-c Tn increased the diagnostic sensitivity of AMI(56.1%vs.63.9%,P<0.001;82.7%vs.84.3%,P=0.025).In contrast,combining CK-MB and hs-c Tn did not change the sensitivity compared with hs-c Tn alone(95.0%vs.95.0%,P>0.999).In the subgroup analysis,the sensitivity of combining CKMB and c-c Tn increased with time from symptom onset<6 h compared with c-c Tn alone(72.8%vs.75.0%,P=0.046),while the sensitivity did not increase with time from symptom onset>6 h(97.5%vs.98.3%,P=0.317).The AUC of the combination of CK-MB and POC-c Tn significantly increased compared to the single POC-c Tn assay(0.776 vs.0.750,P=0.002).The AUC of the combined CKMB and c-c Tn/hs-c Tn assays did not significantly decrease compared with that of the single c-c Tn/hs-c Tn assays within 6 h.CONCLUSIONS:The combination of CK-MB and POC-c Tn or c-c Tn may be valuable for the early diagnosis of AMI,especially when hs-c Tn is not available.展开更多
Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 pa...Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 patients with amyotrophic lateral sclerosis and 582 age-and sexmatched healthy controls.All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology,West China Hospital,China,between May 2008 and December 2018.Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls.Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls.Compared with patients with bulbar-onset amyotrophic lateral sclerosis,patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels.Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index,Amyotrophic lateral Sclerosis Functional Rating ScaleRevised score,or progression rate.After adjusting for prognostic covariates,higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients.We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients;serum creatine kinase levels were decreased at the second blood test,which was sampled at least 6 months after the first blood test.Together,our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients.This study received ethical approval from the Ethics Committee of West China Hospital,China(approval No.2015(236))on December 23,2015.展开更多
Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of t...Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quantifying technique was used to detect the CK BB activity in the cerebrospinal fluid(CSF) of 117 patients with acute head injury and 12 patients with increased intracranial pressure and 20 normal people.Results The CSF CK BB activity of the patients with acute head injury was remarkably higher than that of the normal people and the CSF CK BB activity increased with the seriousness of brain damage.There was a close relationship between CSF CK BB activity and prognosis,and higher activity of CSF CK BB indicated poor prognosis.Conclusion CSF CK BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.展开更多
AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two...AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.展开更多
Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying...Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups: patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio 【 0. 5. Patients with UAP( + ) had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P 【 0. 05) . Serum enzyme concentrations of展开更多
The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divid...The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2 3 ), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.展开更多
BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects ...BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College. MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P < 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P < 0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.展开更多
Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated ne...Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.展开更多
BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the ...BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.展开更多
BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its d...BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.展开更多
Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The asse...Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.展开更多
Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA s...Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.展开更多
BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially ori...BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar con-junctiva.CASE SUMMARY A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months,accompanied by swelling and pain that had per-sisted for 3 d.Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye.Microscopically,the tumor was com-posed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells.Immunophenotypically,the neoplastic cells were positive for ALK,CD10,CD138,Kappa,MUM1,BOB.1,OCT-2,CD4,CD45,EMA,CD79a,CD38,and AE1/AE3,and negative for CD20,PAX5,Lambda,BCL6,CD30 and all other T-cell antigens.The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearran-gements.Fluorescence in situ hybridization studies did not reveal any BCL2,BCL6 or MYC rearrangements.Furthermore,Epstein-Barr virus was not detected by in situ hybridization in the lesions.Based on the histopathological and imaging examinations,the neoplasm was classified as stage IE ALK-positive LBCL.No further treatments were administered.At the 6,15,and 21 mo postoperative follow-up visits,the patient was in good condition,without obvious discomfort.This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass,which is extremely rare and shares morphological and immunohistochemical features with a variety of other neo-plasms that can result in misdiagnosis.CONCLUSION Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.展开更多
BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM...BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.展开更多
Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of po...Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.展开更多
Carbon quantum dot/carbon dot(CD)exhibiting sustained photoluminescence at longer wavelengths in aqueous solution is difficult to prepare,but has enormous potential in biomedical applications.For the first time,we rep...Carbon quantum dot/carbon dot(CD)exhibiting sustained photoluminescence at longer wavelengths in aqueous solution is difficult to prepare,but has enormous potential in biomedical applications.For the first time,we report the magnesium(II)selective fluorescence enhancement of a red-light emitting anthrarufin and boric acid-derived CD in aqueous solution for direct evaluation of creatine kinase(CK)enzyme activity.The CD displayed visually detectable,intense red fluorescence only in the presence of magnesium ion(Mg^2+)at physiological pH value when irradiated with an ultraviolet(UV)source.Concurrently,a significant increase in steady-state fluorescence intensity and fluorescence lifetime was documented.A time-dependent density functional theory(TD-DFT)analysis displayed a bathochromic shift in UV–visible(vis)absorption,and increased oscillator strength of transition resulting from the selective chelation of Mg^2+withβ-hydroxy keto functionality on the surface of the CD.The CD–Mg^2+assembly was subsequently used to conceptualize the detection of CK directly through the exploration of the differential binding affinity of Mg2+with adenosine triphosphate(ATP),adenosine diphophate(ADP),and CD that is otherwise not possible with commercially available kits as of today.Thus,the report delineated here usher grandeur potential of CD for biological explorations related to Mg2+or ATP sensing and monitoring of Mg^2+-dependent enzymatic activity through a clear understanding of the chemistry.展开更多
Background:Biochemical analyses of N‑terminal pro‑brain natriuretic peptide(NT‑proBNP),cardiac troponin T(cTnT),and creatine kinase MB(CK‑MB)have been reported to be valuable for the auxiliary diagnosis of sudden card...Background:Biochemical analyses of N‑terminal pro‑brain natriuretic peptide(NT‑proBNP),cardiac troponin T(cTnT),and creatine kinase MB(CK‑MB)have been reported to be valuable for the auxiliary diagnosis of sudden cardiac death(SCD)in previous forensic studies.Aims and Objectives:The present study aimed to evaluate the diagnostic efficiency of combined analyses of NT‑proBNP,cTnT and CK‑MB in the pericardial fluid for forensic diagnosis of SCD caused by ischemic heart disease.Materials and Methods:Levels of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid of 132 medicolegal autopsy cases were obtained through electrochemiluminescence method.Results:NT‑proBNP,cTnT,and CK‑MB levels were significantly elevated in SCD cases(P<0.05).Receiver‑operating characteristics(ROC)analysis showed that NT‑proBNP,cTnT,and CK‑MB have diagnostic value for the diagnosis of SCD:NT‑proBNP,cutoff value of 2236 pg/ml;cTnT,cutoff value of 199.51 ng/ml;CK‑MB:cutoff value of 2742.5 ng/ml,and the combined analyses of these three biomarkers have better diagnostic efficiency than each single biomarker alone.Moreover,the causes of SCD were sub‑divided into acute ischemic heart disease,acute myocardial infarction(AMI),and recurrent myocardial infarction subgroups for further analysis,which revealed that the ratio of cTnT/CK‑MB could be used to distinguish AMI with the cutoff value of 0.1085 estimated by ROC analysis.Conclusion:These observations suggested that the postmortem biochemical analyses of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid may assist to diagnose SCD in forensic practice,and the combined analyses of multiple biomarkers have better diagnostic efficiency than each single biomarker alone.On the basis of the postmortem biochemical analyses of NT‑proBNP,cTnT and CK‑MB,combining the ratio of cTnT/CK‑MB could be used to distinguish AMI.展开更多
We studied the relations of intracranial pressure (ICP),creatine kinase (CK) and bralnstem auditory evoked potential (BAEP) in 44 patients with traumatic brain edema who were admitted to our hospital from June 1990 to...We studied the relations of intracranial pressure (ICP),creatine kinase (CK) and bralnstem auditory evoked potential (BAEP) in 44 patients with traumatic brain edema who were admitted to our hospital from June 1990 to February 1991. There were 30 males and 14 females, with age range from 9 to 67 years. The results showed that the abnormal BAEP could reflect the severity of cerebral edema in acute head injury and was related to ICP and serum CK levels. When ICP】30 mmHg (4kPa), the abnormality of BAEP was more obvious than that of the control group (P【0.05); the serum CK levels were also elevated markedly. In patients with ICP over and below 4kPa, the rate of abnormal BAEP was 38.46% and 77.78% respectively (P【0.05). The serum CK level in the normal group or in the group with moderate abnormality of BAEP was significantly different from that in the group with severe abnormality or lack of BAEP (274.8± 98.24 U/L vs 705.3± 364.27 U/L; P【0.001). After treatment, the ICP returned to normal, and the BAEP展开更多
Although refolding of fully denatured protein molecules in vitro is not a valid model of folding of the nascent peptide chain in a biologically active protein in vivo, it can provide some useful information for protei...Although refolding of fully denatured protein molecules in vitro is not a valid model of folding of the nascent peptide chain in a biologically active protein in vivo, it can provide some useful information for protein folding. Therefore, refolding of denatured proteins has been extensively studied in recent years. It has been previously reported that during the refolding of guanidine or urea denatured creatine kinase, the enzymatic activity and the na-展开更多
基金This study was supported by grants from the National Key R&D Program of China (2017YFC0908700, 2017YFC0908703)National S&T Fundamental Resources Investigation Project (2018FY100600, 2018FY100602)+2 种基金Taishan Pandeng Scholar Program of Shandong Province (tspd20181220)Taishan Young Scholar Program of Shandong Province (tsqn20161065, tsqn201812129)Key R&D Program of Shandong Province (2020SFXGFY03, 2019GSF108073)
文摘BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine kinase-myocardial band isoenzyme(CK-MB)combined with different cardiac troponin(c Tn)assays in AMI diagnosis.METHODS:This multicenter,observational study included 3,706 patients with acute chest pain from September 1,2015,to September 30,2017.We classified the participants into three groups according to the c Tn assays:the point-of-care c Tn(POC-c Tn)group,the contemporary c Tn(c-c Tn)group,and hs-c Tn group.The diagnostic value was quantified using sensitivity and the area under the curve(AUC).RESULTS:Compared to the single POC-c Tn/c-c Tn assays,combining CK-MB and POC-c Tn/c-c Tn increased the diagnostic sensitivity of AMI(56.1%vs.63.9%,P<0.001;82.7%vs.84.3%,P=0.025).In contrast,combining CK-MB and hs-c Tn did not change the sensitivity compared with hs-c Tn alone(95.0%vs.95.0%,P>0.999).In the subgroup analysis,the sensitivity of combining CKMB and c-c Tn increased with time from symptom onset<6 h compared with c-c Tn alone(72.8%vs.75.0%,P=0.046),while the sensitivity did not increase with time from symptom onset>6 h(97.5%vs.98.3%,P=0.317).The AUC of the combination of CK-MB and POC-c Tn significantly increased compared to the single POC-c Tn assay(0.776 vs.0.750,P=0.002).The AUC of the combined CKMB and c-c Tn/hs-c Tn assays did not significantly decrease compared with that of the single c-c Tn/hs-c Tn assays within 6 h.CONCLUSIONS:The combination of CK-MB and POC-c Tn or c-c Tn may be valuable for the early diagnosis of AMI,especially when hs-c Tn is not available.
基金supported by the National Natural Science Foundation of China,No.81301093(to XPC)。
文摘Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 patients with amyotrophic lateral sclerosis and 582 age-and sexmatched healthy controls.All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology,West China Hospital,China,between May 2008 and December 2018.Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls.Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls.Compared with patients with bulbar-onset amyotrophic lateral sclerosis,patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels.Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index,Amyotrophic lateral Sclerosis Functional Rating ScaleRevised score,or progression rate.After adjusting for prognostic covariates,higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients.We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients;serum creatine kinase levels were decreased at the second blood test,which was sampled at least 6 months after the first blood test.Together,our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients.This study received ethical approval from the Ethics Committee of West China Hospital,China(approval No.2015(236))on December 23,2015.
文摘Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quantifying technique was used to detect the CK BB activity in the cerebrospinal fluid(CSF) of 117 patients with acute head injury and 12 patients with increased intracranial pressure and 20 normal people.Results The CSF CK BB activity of the patients with acute head injury was remarkably higher than that of the normal people and the CSF CK BB activity increased with the seriousness of brain damage.There was a close relationship between CSF CK BB activity and prognosis,and higher activity of CSF CK BB indicated poor prognosis.Conclusion CSF CK BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.
基金Supported by the Taiwan Biotech Co., Taiwan, China
文摘AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.
文摘Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups: patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio 【 0. 5. Patients with UAP( + ) had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P 【 0. 05) . Serum enzyme concentrations of
文摘The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2 3 ), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.
基金Shenzhen Science and Technology Bureau, No.200405204
文摘BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College. MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P < 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P < 0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.
文摘Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.
基金Supported by The Suzhou Science and Technology Development Plan Guiding Project,No.SZSYYXH-2023-YB5The Suzhou Science and Technology Development Plan Project,No.SKY2023002The Suzhou Key Laboratory of Children's Structural Deformities,No.SZS2022018.
文摘BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.
基金Supported by National Natural Science Foundation of China,No.82260211Key Research and Development Project in Jiangxi Province,No.20203BBG73058Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166.
文摘BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.
文摘Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.
基金supported by the BK21 FOUR funded by the Ministry of Education,Republic of Korea,the National Research Foundation of Korea(NRF-2022R1F1A1066642,RS-2023-00272063)grant funded by the Korean government(MSIT),and POSTECH Basic Science Research Institute Grant(NRF-2021R1A6A1A10042944).Research was also supported by funds donated by Dr.Jae Kyu Lee and Mr.Jason Gim.Following are results of a study on the“Leaders in INdustry-University Cooperation 3.0”Project,supported by the Ministry of Education and National Research Foundation of Korea.
文摘Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.
文摘BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar con-junctiva.CASE SUMMARY A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months,accompanied by swelling and pain that had per-sisted for 3 d.Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye.Microscopically,the tumor was com-posed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells.Immunophenotypically,the neoplastic cells were positive for ALK,CD10,CD138,Kappa,MUM1,BOB.1,OCT-2,CD4,CD45,EMA,CD79a,CD38,and AE1/AE3,and negative for CD20,PAX5,Lambda,BCL6,CD30 and all other T-cell antigens.The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearran-gements.Fluorescence in situ hybridization studies did not reveal any BCL2,BCL6 or MYC rearrangements.Furthermore,Epstein-Barr virus was not detected by in situ hybridization in the lesions.Based on the histopathological and imaging examinations,the neoplasm was classified as stage IE ALK-positive LBCL.No further treatments were administered.At the 6,15,and 21 mo postoperative follow-up visits,the patient was in good condition,without obvious discomfort.This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass,which is extremely rare and shares morphological and immunohistochemical features with a variety of other neo-plasms that can result in misdiagnosis.CONCLUSION Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.
基金This study was reviewed and approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangxi Medical University(Approval No.2023-E386-01).
文摘BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.
基金funded by the Natural Science Foundation of Higher Education Institutions of Auhui Province(Grant No.KJ2021A0352)the Research Fund Project of Anhui Medical University(Grant No.2020xkj236)Applied Medicine Research Project of Hefei Health Commission(Grant No.HWKJ2019-172-14).
文摘Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.
文摘Carbon quantum dot/carbon dot(CD)exhibiting sustained photoluminescence at longer wavelengths in aqueous solution is difficult to prepare,but has enormous potential in biomedical applications.For the first time,we report the magnesium(II)selective fluorescence enhancement of a red-light emitting anthrarufin and boric acid-derived CD in aqueous solution for direct evaluation of creatine kinase(CK)enzyme activity.The CD displayed visually detectable,intense red fluorescence only in the presence of magnesium ion(Mg^2+)at physiological pH value when irradiated with an ultraviolet(UV)source.Concurrently,a significant increase in steady-state fluorescence intensity and fluorescence lifetime was documented.A time-dependent density functional theory(TD-DFT)analysis displayed a bathochromic shift in UV–visible(vis)absorption,and increased oscillator strength of transition resulting from the selective chelation of Mg^2+withβ-hydroxy keto functionality on the surface of the CD.The CD–Mg^2+assembly was subsequently used to conceptualize the detection of CK directly through the exploration of the differential binding affinity of Mg2+with adenosine triphosphate(ATP),adenosine diphophate(ADP),and CD that is otherwise not possible with commercially available kits as of today.Thus,the report delineated here usher grandeur potential of CD for biological explorations related to Mg2+or ATP sensing and monitoring of Mg^2+-dependent enzymatic activity through a clear understanding of the chemistry.
基金funded by the National Natural Science Foundation of China(Grant No.82002001).
文摘Background:Biochemical analyses of N‑terminal pro‑brain natriuretic peptide(NT‑proBNP),cardiac troponin T(cTnT),and creatine kinase MB(CK‑MB)have been reported to be valuable for the auxiliary diagnosis of sudden cardiac death(SCD)in previous forensic studies.Aims and Objectives:The present study aimed to evaluate the diagnostic efficiency of combined analyses of NT‑proBNP,cTnT and CK‑MB in the pericardial fluid for forensic diagnosis of SCD caused by ischemic heart disease.Materials and Methods:Levels of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid of 132 medicolegal autopsy cases were obtained through electrochemiluminescence method.Results:NT‑proBNP,cTnT,and CK‑MB levels were significantly elevated in SCD cases(P<0.05).Receiver‑operating characteristics(ROC)analysis showed that NT‑proBNP,cTnT,and CK‑MB have diagnostic value for the diagnosis of SCD:NT‑proBNP,cutoff value of 2236 pg/ml;cTnT,cutoff value of 199.51 ng/ml;CK‑MB:cutoff value of 2742.5 ng/ml,and the combined analyses of these three biomarkers have better diagnostic efficiency than each single biomarker alone.Moreover,the causes of SCD were sub‑divided into acute ischemic heart disease,acute myocardial infarction(AMI),and recurrent myocardial infarction subgroups for further analysis,which revealed that the ratio of cTnT/CK‑MB could be used to distinguish AMI with the cutoff value of 0.1085 estimated by ROC analysis.Conclusion:These observations suggested that the postmortem biochemical analyses of NT‑proBNP,cTnT,and CK‑MB in the pericardial fluid may assist to diagnose SCD in forensic practice,and the combined analyses of multiple biomarkers have better diagnostic efficiency than each single biomarker alone.On the basis of the postmortem biochemical analyses of NT‑proBNP,cTnT and CK‑MB,combining the ratio of cTnT/CK‑MB could be used to distinguish AMI.
文摘We studied the relations of intracranial pressure (ICP),creatine kinase (CK) and bralnstem auditory evoked potential (BAEP) in 44 patients with traumatic brain edema who were admitted to our hospital from June 1990 to February 1991. There were 30 males and 14 females, with age range from 9 to 67 years. The results showed that the abnormal BAEP could reflect the severity of cerebral edema in acute head injury and was related to ICP and serum CK levels. When ICP】30 mmHg (4kPa), the abnormality of BAEP was more obvious than that of the control group (P【0.05); the serum CK levels were also elevated markedly. In patients with ICP over and below 4kPa, the rate of abnormal BAEP was 38.46% and 77.78% respectively (P【0.05). The serum CK level in the normal group or in the group with moderate abnormality of BAEP was significantly different from that in the group with severe abnormality or lack of BAEP (274.8± 98.24 U/L vs 705.3± 364.27 U/L; P【0.001). After treatment, the ICP returned to normal, and the BAEP
文摘Although refolding of fully denatured protein molecules in vitro is not a valid model of folding of the nascent peptide chain in a biologically active protein in vivo, it can provide some useful information for protein folding. Therefore, refolding of denatured proteins has been extensively studied in recent years. It has been previously reported that during the refolding of guanidine or urea denatured creatine kinase, the enzymatic activity and the na-
