OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective To investigate the effects of laparoscopic sleeve gastrectomy(LSG)on the cardiac structure and function in obese patients with heart failure(HF)and compare the efficacy of LSG across obese patients with different HF types.Methods This study included 33 obese patients with HF who underwent LSG.The clinical indicators were compared between before operation and 12 months after operation.Repeated measures analysis of variance was employed to evaluate the changes in echocardiographic parameters before operation and 3,6,and 12 months after operation.Patients were allocated into a HF with preserved ejection fraction group(n=17),a HF with mildly reduced ejection fraction group(n=5)and a HF with reduced ejection fraction(HFrEF)group(n=11)based on left ventricular ejection fraction(LVEF)before operation for subgroup analyses of the effects of LSG on the cardiac structure and function of obese patients with HF.The paired samples t-test was conducted to assess the degree of cardiac structural and functional alterations after LSG.Results The 33 patients included 69.7% males,with an average age of(35.3±9.9)years,and a body mass index(BMI)of(51.2±9.8)kg/m².The median follow-up was 9.0(5.0,13.3)months.Compared with the preoperative values,the postoperative BMI(P=0.002),body surface area(BSA)(P=0.009),waist circumference(P=0.010),hip circumference(P=0.031),body fat content(P=0.007),and percentage of patients with cardiac function grades Ⅲ-IV(P<0.001)decreased.At the 12-month follow-up left atrial diameter(P=0.006),right atrial long-axis inner diameter(RAD1)(P<0.001),right atrial short-axis inner diameter(RAD2)(P<0.001),right ventricular inner diameter(P=0.002),interventricular septal thickness at end-diastolic(P=0.002),and left ventricular end-diastolic volumes(P=0.004)and left ventricular end-systolic volumes(P=0.003) all significantly reduced compared with preoperative values.Additionally,left ventricular fractional shortening and LVEF improved(both P<0.001).Subgroup analyses revealed that cardiac structural parameters significantly decreased in the HF with preserved ejection fraction,HF with mildly reduced ejection fraction,and HFrEF subgroups compared with preoperative values.Notably,the HFrEF group demonstrated the best performance in terms of left atrial diameter(P=0.003),left ventricular inner diameter at end-diastole(P=0.008),RAD1(P<0.001),RAD2(P=0.004),right ventricular inner diameter(P=0.019),left ventricular end-diastolic volume(P=0.004)and left ventricular end-systolic volume(P=0.001),cardiac output(P=0.006),tricuspid regurgitation velocity(P=0.002),and pulmonary artery systolic pressure(P=0.001) compared to preoperatively.Postoperative left ventricular fractional shortening(P<0.001,P=0.003,P<0.001)and LVEF(P<0.001,P=0.011,P=0.001)became higher in all the three subgroups than the preoperative values.Conclusions LSG decreased the body weight,BMI,and BSA,improved the cardiac function grade,reversed the enlargement of the left atrium and left ventricle,reduced the right atrium and right ventricle,and enhanced the left ventricular systolic function.It was effective across obese patients with different HF types.Particularly,LSG demonstrates the best performance in improving the structures of both atria and ventricles in obese patients with HFrEF.
Humans ; Male ; Female ; Gastrectomy/methods* ; Heart Failure/complications* ; Adult ; Obesity/physiopathology* ; Laparoscopy ; Middle Aged ; Heart/physiopathology* ; Stroke Volume

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

OBJECTIVE: To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type I (OFD1). METHODS: A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing. RESULTS: The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c.224A>G (p.Asn75Ser) variant of the OFD1 gene. The same variant was not found among healthy members from her pedigree. CONCLUSION The c.224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum of OFD1 gene variants.
Humans ; Female ; Pedigree ; Orofaciodigital Syndromes/genetics* ; East Asian People ; Phenotype ; Heterozygote ; Mutation ; China

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.
Humans ; Integrative Medicine ; Brain/pathology* ; Cerebral Small Vessel Diseases/pathology* ; Stroke/complications* ; Cognitive Dysfunction/complications* ; Magnetic Resonance Imaging

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P>0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.
Child ; Female ; Humans ; Male ; Aftercare ; Cardiopulmonary Resuscitation/methods* ; Cross-Sectional Studies ; Death, Sudden, Cardiac/prevention & control* ; East Asian People ; Heart Arrest/therapy* ; Patient Discharge ; Retrospective Studies ; Surveys and Questionnaires

OBJECTIVE: To investigate the associated factors of endogenous erythropoietin (EPO) and its association with 10-year risks of atherosclerotic cardiovascular disease in a Chinese community-based general population. METHODS: The participants of this study were from an atherosclerosis cohort survey which was established by the Department of Cardiology, Peking University First Hospital in 2011. The cohort survey was performed in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China. The inclusion criteria of this study were: (1) endogenous EPO was measured; (2) health questionnaire data and other clinical data were complete; (3) participatants who had cardiovascular or cerebrovascular diseases (defined as self-reported coronary heart disease, stroke or transient ischemic attack) or anemia or estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m²) at baseline were excluded. Multivariate linear regression model was used to examine the associated factors of endogenous EPO. The participants were grouped into low (< 5%), moderate (5%-10%) and high risk (≥10%) groups, based on predicted 10-year cardiovascular disease risk using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) equations. RESULTS: A total of 4 013 participants were included. Mean age of them was (55.9±8.2) years, 62.2% (n=2 496) of them were female, and 46.3% (n=1 859), 70.9% (n=2 845), 21.9% (n=879) had hypertension, dyslipidemia and diabetes, individually. The average body mass index was (26.1±3.3) kg/m². The median of EPO level was 12.8 (9.3-17.4) IU/L and 25.1% (n=998) were at high 10-years risk of cardiovascular disease. Hemoglobin (β=-0.05, 95%CI: -0.07 to -0.04) and eGFR ≥90 mL/(min·1.73 m²) (β=-0.05, 95%CI: -0.07 to -0.04) were associated with lower in transformed EPO levels while hypertension (β=0.08, 95%CI: 0.05 to 0.12) and obesity (β=0.14, 95%CI: 0.09 to 0.18) were associated with higher in transformed EPO levels in multivariate linear regression analyses. Ten-year cardiovascular disease risks were positively associated with in transformed EPO levels (β=0.07, 95%CI: 0.05 to 0.09). The participants at moderate and high cardiovascular disease risks had significant higher EPO levels than the low risk group (all P < 0.05). CONCLUSION In community-based Beijing populations, endogenous EPO was associated with hemoglobin, renal function, obesity and hypertension. Individuals at high 10-years cardiovascular disease risks have higher endogenous EPO levels. Endogenous EPO may be a potential risk marker of cardiovascular disease.
Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/epidemiology* ; Erythropoietin ; Hemoglobins ; Hypertension/epidemiology* ; Obesity ; Risk Factors