OBJECTIVE To investigate the metabolic changes in MEG-01 megakaryocytes after treatment with linezolid （LZD） from metabolomic perspective and its impact on the the proliferation of cells and generation of platelet precursors. METHODS MEG-01 cells were seeded in proliferation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 100， 200， 400， 800 μg/mL LZD groups. The proliferation status of cells in each group was observed under the microscope； cell proliferation and viability were assessed. Cells were also seeded in differentiation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 400 μg/mL LZD group； after 14 days of culture， platelet precursor generation was observed under the microscope； immunofluorescence staining was performed to count the proportion of cells producing pseudopodia， the relative length of pseudopodia was measured， and the expression levels of CD41 and CD42b mRNA were assessed. Cells from the solvent control group and the 400 μg/mL LZD group， cultured in differentiation medium for 14 days， were extracted and subjected to non-targeted metabolomics and targeted energy metabolomics analysis using liquid chromatography-tandem mass spectrometry. The relative content of pyruvate in cells， after being cultured for 14 days with the addition of pyruvate （10 mmol/L） or LZD （400 μg/mL）+pyruvate （10 mmol/L）， was measured and observed， as well as its effects on cell proliferation and platelet precursor generation. RESULTS 400 μg/mL LZD could significantly inhibit the proliferation of MEG-01 cells and the generation of platelet precursors （P＜0.01）. Non-targeted metabolomic analysis of MEG-01 cells after 400 μg/mL LZD treatment revealed significant changes in energy metabolism-related pathways such as mTOR signaling pathway， alanine， aspartate and glutamate metabolism， and central carbon metabolism in cancer. Targeted energy metabolomic analysis further showed that the relative contents of adenosine triphosphate， guanosine triphosphate， and pyruvate in MEG-01 cells were significantly reduced （P＜0.01）， while the relative contents of lactate were significantly increased （P＜0.01）. Compared with the LZD group， the relative content of pyruvate， cell count， the proportion of cells producing pseudopodia and the relative length of pseudopodia were significantly increased in the LZD+pyruvate group （P＜0.01）. CONCLUSIONS LZD may reduce pyruvate production by inhibiting mitochondrial energy metabolism， thereby suppressing megakaryocyte proliferation and platelet precursor production， ultimately leading to the occurrence of thrombocytopenia.

Objective:To develop and validate a risk prediction model for cognitive frailty in elderly patients with type 2 diabetes.Methods:A total of 483 elderly patients with type 2 diabetes who visited Tianjin First Central Hospital from June to December 2022 were selected using convenience sampling. They were randomly divided into a modeling group ( n=338) and a validation group ( n=145). Data were collected using a self-designed general information questionnaire, the Short-Form Mini Nutritional Assessment (MNA-SF), the Geriatric Depression Scale-15 (GDS-15), the Frailty Phenotype (FP), the Montreal Cognitive Assessment (MoCA), and the Clinical Dementia Rating (CDR). Logistic regression analysis was performed to identify the influencing factors. A cognitive frailty risk prediction nomogram model was constructed based on the results. The model was validated in the validation group, and its predictive performance and clinical applicability were evaluated using the area under the receiver operating characteristic curve ( AUC), calibration curve, and clinical decision curve analysis. A total of 483 questionnaires were distributed and all were returned as valid, resulting in a 100.0% response rate. Results:The prevalence of cognitive frailty in the 483 elderly patients with type 2 diabetes was 20.3% (98/483). Age, regular exercise, duration of diabetes, HbA1c levels, depression and nutritional status were identified as predictive factors in the model. The AUC of the model was 0.886, and the Hosmer-Lemeshow test showed a χ 2 value of 8.004 ( P=0.433). The optimal cutoff value was 0.335, and the accuracy was 89.0%. Conclusions:The prediction model demonstrates good fit and strong predictive performance, and can intuitively and easily identify elderly patients with type 2 diabetes who are at high risk of cognitive frailty, providing a reference for early screening and intervention.

Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Objective:To explore the differences of risk stratification of very high-risk or extreme high-risk atherosclerotic cardiovascular diseases (ASCVD) and the attainment rates of low-density lipoprotein cholesterol (LDL-C) management targets evaluated by three different criteria, and the causal attributions of these differences.Methods:Patients with ASCVD were consecutively enrolled from January 1 to December 31 in 2019, and were evaluated for very high-risk or extreme high-risk and LDL-C goal attainment rates with 2018 American guideline on the management of blood cholesterol (2018AG), 2019 China Cholesterol Education Program (CCEP) Expert Advice for the management of dyslipidemias (2019EA) and 2020 Chinese expert consensus on lipid management of very high-risk ASCVD patients(2020EC), respectively. The causal attributions of the differences in attainment rates were analyzed as well.Results:A total of 1 864 ASCVD patients were included in this study. According to 2018AG, 2019EA and 2020EC, the proportions of the patients with very high-risk or extreme high-risk were 59.4%, 90.7%, and 65.6%, respectively. The absolute LDL-C target attainment rates were 37.2%, 15.7%, and 13.7%, respectively, the differences between each two rates were statistically significant (all P<0.001). As to the differences in attainment rates between 2020EC and 2018AG, 61.5% were due to the different LDL-C goal attainment values and 38.5% were caused by the different risk stratifications, while for the differences between 2020EC and 2019EA attainment rates, different LDL-C goal attainment values were responsible for 13.2%, and different risk stratifications were responsible for 86.8% of the differences. Conclusions:There are significant differences in the proportions and LDL-C attainment rates among the three different criteria for very high-risk or extreme high-risk ASCVD. 2020EC showed a moderate proportion of patients with extreme high-risk, and had the lowest LDL-C attainment rate. The differences between 2020EC and 2018AG are mainly due to the LDL-C target values, and the differences between 2020EC and 2019EA are mainly caused by the risk stratifications.

Objective:To study effects of multilevel nutritional support based on Nutrition Risk Screening (NRS 2002) on nutritional status and prognosis of patients with craniocerebral tumor surgery.Methods:A total of 40 patients undergoing craniocerebral tumor surgery who were admitted to The Third People's Hospital of Hubei Province from November 2018 to October 2019 were included as the control group. A total of 40 patients undergoing craniocerebral tumor surgery who were admitted to the Third People's Hospital of Hubei Province from November 2019 to November 2020 were included as the observation group. The control group was given routine nutritional support, and the observation group was given multi-level nutritional support based on NRS 2002. The nutritional status, serum nutritional indexes, prognosis and complications were compared between the two groups before the intervention and one month after the intervention.Results:After 1 month of intervention, the thickness of triceps skinfold and muscle circumference of unaffected upper arm in the two groups were greater than those before intervention, and those of the observation group were greater than the control group, and the differences were statistically significant ( P<0.05) . The levels of prealbumin, albumin and hemoglobin in the two groups were higher than those before the intervention, and the observation group were higher than the control group, and the differences were statistically significant ( P<0.05) . The Glasgow score and ability of daily living score of the two groups were higher than those before the intervention, and the observation group were higher than the control group, and the differences were statistically significant ( P<0.05) . After 1 month of intervention, there were no statistically significant differences in body mass index, constipation, diarrhea, pulmonary infection and malnutrition between the two groups ( P>0.05) . Conclusions:Multilevel nutritional support based on NRS 2002 can improve the nutritional status and prognosis of patients undergoing craniocerebral tumor surgery and the application effect is good.

Objective To investigate the safety and effectiveness of ultrasound-guided paravertebral anaes-thesia combined with propofol in the thoracoscopic sympathectomy. Methods Total 63 male and 59 female patients with hyperhidrosis were recruited. The patients were equally divided into two groups:group A and C. Patients in group A received ultrasound-guided paravertebral anaesthesia combined with propofol. Patients in group C received general intravenous anesthesia with endotracheal intubation. The heart rate (HR),mean arterial pres-sure(MAP)and the oxygen saturation(SpO2)at the time of entering the operating room(T0),completing anesthe-sia(T1),incising the skin(T2),cutting the T4 sympathetic trunk(T3),completing the operation were record-ed. The awake time after operation ,VAS score after operation and postoperative throat discomfort were also record-ed. Results The two groups successfully completed the surgery. There were no significant differences of the HR , MAP and SpO2 at T0-T4 between the two groups. There were significant differences of the awake time after opera-tion,postoperative feeding time and hospitalization expenses. The VAS score after operation of group A were better than group C(P<0.05)at T2 h,T4 h,T8 h,and T12 h. There was no significant difference of VAS score at T24 h between the two groups. Conclusion Ultrasound-guided paravertebral anaesthesia combined with propofol can pro-vide a safe and effective approach for patients receiving the thoracoscopic sympathectomy.

Objective To observe the features of the full field electroretinogram (FF-ERG) in type 1 diabetes (T1D) children without diabetic retinopathy (DR).Methods Retrospective case study.Forty-one T1D children and 25 age-matched normal controls underwent a complete ophthalmic examination,including best-corrected visual acuity,refraction,intraocular pressure,slit lamp,fundus photography,indirect ophthalmoscopy,and spectral domain optical coherence tomography to exclude DR.All FF-ERG tests were performed by an experienced technician.The ERG series includes six protocols:dark-adapted 0.01 ERG (r-b 0.01);dark-adapted 3 ERG (mix-a 3.0,mix-b 3.0);dark-adapted 10 ERG (mix-a 10.0,mix-b 10.0);dark-adapted oscillatory potentials (OPS);light-adapted 3 ERG (c-a 3.0,c-b 3.0);light-adapted 30 Hz flicker (30 Hz FP) ERG.To compare the amplitudes and implicit times of the FF-ERG between the T1D and control group children.Results Compared with the control subjects,the FF-ERG amplitudes decreased and the implicit times increased in T1D.Except for r-b 0.01 (t =-0.228,P＞0.05),the amplitudes of other FF-ERGs were all significantly attenuated (t =-1.664,-3.645,-4.324,-6.123,-5.846,-12.9,-14.4,-5.23;P＜0.05) in T1D children.The implicit times of mix-b 3.0,mix-b 10.0,c-b 3.0 and OP2 significantly increased (t=5.242,2.879,5.378,3.506;P＜0.05).The implicit times of r-b 0.01,mix-a 3.0,mix-a 10.0,c-a 3.0 and 30Hz FP changes were not significantly (t=2.331,1.677,0.557,0.84,0.064;P ＞ 0.05).Conclusion The FF-ERG amplitudes decreased and implicit times increased in T1D children compared with the control normal subjects.

Objective To investigate the effect of 20‐HETE on the isolated myocardial ischemia reperfusion injury and to ex‐plore its underlying mechanisms .Methods Experiments were performed in isolated rat hearts subjected to 35 min of ischemia fol‐lowed by 40 min of reperfusion in Langendorff preparations .HET0016 (1 μmol/L) and various concentrations (10 ,30 or 50 nmol/L) of 20‐HETE were infused 10 min before the onset of ischemia and throughout the reperfusion period .Cardiac hemodynamic changes and myocardial contractility were continuously recorded with the Powerlab /8P system .Myocardial infarct size was meas‐ured by TTC staining .The level of ROS and the protein carbonyl content were determined by DHE fuorescence and DNPH method , respectively .Results Perfusion with HET0016 significantly improved myocardial ischemia reperfusion injury reduction in cardiac contractility ,after inhibited the production of 20‐HETE significantly reduced the occurrence of myocardial infarction area (P<0 .05) ,but exogenous join 20‐HETE aggravated I/R‐induced myocardial injury (P<0 .05) .Myocardial ischemia reperfusion injury significantly increased production of ROS and oxidative stress ,both of which were significantly inhibited by HET 0016 and enhanced by 20‐HETE administration(P< 0 .05) .Conclusion 20‐HETE stimulates ROS production and enhance protein carbonylation , which aggravates myocardial ischemia reperfusion injury .

Objective: To describe the clinical characteristics with long-term prognosis in patients with mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHCM).
Methods: A total of 66 MVOHCM patients treated in our hospital were retrospectively studied for their morbidity, clinical characteristics and mortality. The cumulative survival rate was calculated by Kaplan-Meier method; the risk factors for cardiac death and cardiovascular events were analyzed by uni- and multivariate Cox proportional hazard model.
Results: There were 66 (2.74%) patients suffering from MVOHCM among 2413 patients of hypertrophic cardiomyopathy and the average diagnostic age was (40.16 ± 14.64) years. With (7.30 ± 6.25) years of follow-up study, the cardiovascular mortality was 13.6% and unexplained syncope (HR=13.37, 95% CI: 1.65-114.46, P=0.015) was the independent predictor for cardiovascular death. There were 45.45% (30/66) patients experienced at least 1 time of cardiovascular event and the most frequent one was non-sustained ventricular tachycardia (NSVT); 19.70% (13/66) of patients combined with apical aneurysms, and they were more inclined to experience NSVT.
Conclusion: MVOHCM patients usually have unfavorable prognosis with the higher incidence of cardiovascular events, some patients may develop apical aneurysm. The early diagnosis of MVOHCM is important for appropriate treatment.

BACKGROUNDWhether two clopidogrel pretreatment strategies prior to elective percutaneous coronary intervention (PCI): a 300 mg loading dose (LD) in clopidogrel naїve patients and a 75 mg maintenance dose (MD) once daily in patients on chronic clopidogrel therapy play the same role in the platelet inhibition in Chinese with different CYP2C19 genotypes remains unknown. We aim to evaluate the impact on platelet inhibition by clopidogrel pretreatment strategy and its interaction effect with CYP2C19 genotype.

METHODSChinese patients undergoing PCI (n = 840) were assigned to 2×2 groups in the trial according to different clopidogrel pretreatment strategies (470 patients in LD, 370 patients in MD) and CYP2C19 genotypes (494 carriers of any CYP2C19 *2 or *3 loss-of-function allele, 346 non-carriers). The primary outcome was platelet aggregation (PA) as measured by the 10 µmol/L adenosine diphosphate induced light transmission aggregation.

RESULTSCompared with MD group, LD strategy showed a significantly higher PA-((59.22 ± 11.67)% vs. (52.83 ± 12.17)%, P < 0.01), similar PA difference was observed in CYP2C19 loss-of-function carriers compared with non-carriers ((59.41 ± 10.91)% vs. (52.10 ± 12.90)%, P < 0.01). LD patients in either the CYP2C19 loss-of-function allele carrier or non-carrier group showed a significantly higher PA compared with MD group ((61.50 ± 10.61)% vs. (56.84 ± 10.74)%, P < 0.01; (56.06 ± 12.34)% vs. (46.88 ± 11.78)%, P < 0.01, respectively). A quantitative interaction effect was observed between clopidogrel pretreatment strategy and CYP2C19 genotype (P = 0.001).

CONCLUSIONThe 300 mg LD strategy results in a decreased effect on platelet inhibition compared with the 75 mg MD in Chinese patients receiving clopidogrel prior to PCI, especially in the CYP2C19 2 or 3 loss-of-function allele non-carriers. (ClinicalTrials.gov number NCT01710436)

Aged ; Blood Platelets ; drug effects ; Coronary Artery Disease ; surgery ; Cytochrome P-450 CYP2C19 ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; methods ; Platelet Aggregation ; drug effects ; Prospective Studies ; Ticlopidine ; analogs & derivatives ; therapeutic use