Objective:To investigate the value of left ventricular systolic synchrony assessed by gated myocardial perfusion imaging(GMPI)in predicting major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease(CHD).Methods:In this retrospective study, clinical data from elderly patients who had completed a two-day assessment of resting-loading GMPI between September 2012 and February 2014 in Beijing Hospital were collected, including the summed stress score(SSS)for total ischemic burden, measured by GMPI, left ventricular ejection fraction(LVEF), peak filling rate(PFR), phase band width(PBW), phase standard deviation(PSD)and phase entropy(PE).Follow-up of MACE was conducted.Independent risk factors for MACE were analyzed using a multifactorial Cox proportional hazards regression model, and the cumulative MACE incidence was analyzed using the Kaplan-Meier survival curve.Results:A total of 427 subjects were enrolled, including 200(46.8%)men, with a mean age of 74.1±6.5(60-92)years and 323(75.6%)aged ≥ 70 years.The median follow-up time was 54.7 months.At the end of follow-up, MACE occurred in 47 patients(11.0%).Compared with the group without MACE, the incidences of hypertension, hyperlipidemia, and hyperuricemia were significantly higher( χ2=5.20, 5.62, 3.86, all P<0.05), LVEF and PFR were significantly lower( t=-5.51, -5.23, both P<0.001), and SSS, PSD, PBW, and PE were significantly higher( Z=4.78, t=5.14, 5.78, 5.62, all P<0.001)in the MACE group.The results of Cox proportional hazards regression model analysis suggested that age ≥ 70(hazard ratio: 2.57, 95% CI: 1.08-6.13), abnormal perfusion(hazard ratio: 2.60, 95% CI: 1.31-5.15), increased PSD(hazard ratio: 3.72, 95% CI: 1.72-8.05)and increased PE(hazard ratio: 4.09, 95% CI: 1.94-8.63)were independent risk factors for the occurrence of MACE(all P<0.05).Further analysis on 323 patients ≥ 70 years indicated that abnormal perfusion(hazard ratio: 2.96, 95% CI: 1.40-6.26), increased PSD(hazard ratio: 3.51, 95% CI: 1.56-7.89), and increased PE(hazard ratio: 4.49, 95% CI: 2.08-9.71)were independent risk factors for MACE( P<0.05 for all). Conclusions:Parameters of GMPI systolic synchrony analysis can very well identify the population at high risk of MACE in elderly patients with CHD.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

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.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Animals ; Mice ; Network Pharmacology ; AMP-Activated Protein Kinases ; Chromatography, High Pressure Liquid ; NLR Family, Pyrin Domain-Containing 3 Protein ; Sirtuin 1 ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

This paper compared the differences between two kinds of Bufonis Venenum produced by Bufo gargarizans gargarizans and B. gararizans andrewsi, and verified the rationality of the market value orientation of Bufonis Venenum based on the zebrafish mo-del. Twenty batches of Bufonis Venenum from Jiangsu province, Hebei province, Liaoning province, Jilin province, and Liangshan, Sichuan province, including B. gargarizans gargarizans and B. gararizans andrewsi, were collected. The UHPLC-LTQ-Orbitrap-MS combined with principal component analysis was used to compare the differences between two kinds of Bufonis Venenum. According to the limiting conditions of VIP>1, FC<0.5 or FC>2.0, and peak total area ratio>1%, 9 differential markers were determined, which were cinobufagin, cinobufotalin, arenobufagin, resibufogenin, scillaredin A, resibufagin, 3-(N-suberoylargininyl)-arenobufagin, 3-(N-suberoylargininyl)-marinobufagin, and 3-(N-suberoylargininyl)-resibufogenin. The content of 20 batches of Bufonis Venenum was determined according to the Chinese Pharmacopoeia(2020 edition) by high-performance liquid chromatography, and the 2 batches of Bufonis Venenum, CS7(8.99% of total content) and CS9(5.03% of total content), with the largest difference in the total content of the three quality control indexes of the Chinese Pharmacopoeia(bufalin, cinobufagin, and resibufogenin) were selected to evaluate their anti-liver tumor activity based on the zebrafish model. The tumor inhibition rates of the 2 batches were 38.06% and 45.29%, respectively, proving that only using the quality control indexes of the Chinese Pharmacopoeia as the value orientation of Bufonis Venenum market circulation was unreasonable. This research provides data support for the effective utilization of Bufonis Venenum resources and the establishment of a rational quality evaluation system of Bufonis Venenum.
Animals ; Zebrafish ; Bufanolides/analysis* ; Bufonidae ; Chromatography, High Pressure Liquid ; Quality Control ; Cell Line, Tumor

ObjectiveTo assess the value of apparent diffusion coefficient （ADC） in the treatment of uterine fibroid using magnetic resonance guided focused ultrasound surgery （MRgFUS）. MethodsThe MRI and clinical data of 56 patients with uterine fibroid before， at 3 and 6 months after MRgFUS treatment， at Foshan Hospital of Traditional Chinese Medicine from December 2018 to October 2022， were retrospectively analyzed. The correlation between the ADC value and lesion volume， symptoms severity score （SSS） and uterine fibroid symptoms quality of life questionnaire （UFS-QOL） were analyzed. ANOVA was used to compare the differences in related parameters before and after treatment， and Pearson’s method was performed to analyze data correlation. ResultsThere were significant differences in ADC value ［（1.11±0.13）， （1.84±0.09）， （2.12±0.24），×10^-3/（mm²/s）］， lesion volume （102±35.30， 56.70±18.88， 46.93±18.99，cm³）， SSS （36.73±11.74， 21.77±10.21， 17.66±9.30） and UFS-QOL score （59.05±17.48， 76.54±16.50， 82.46±12.37） between before treatment and each time point after treatment （F value was 557.837， 73.589， 53.976 and 37.606， respectively， all P<0.05）. The ADC values were negatively correlated with lesion volume and SSS， and positively correlated with UFS-QOL score， with correlation coefficients of -0.586， -0.630 and 0.592， respectively （all P<0.05）. ConclusionThe ADC value has clinical significance for the treatment of uterine fibroid using MRgFUS.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.
Humans ; Pregnancy ; Female ; Male ; Animals ; Mice ; Teratozoospermia/pathology* ; Semen/metabolism* ; Infertility, Male/metabolism* ; Spermatozoa/metabolism* ; Mutation ; RNA-Binding Proteins/metabolism* ; Cell Cycle Proteins/genetics*