The role of single-cell RNA sequencing in cardiac tumour - a case report.

A 65-year-old woman presented to our hospital with 5 days of chest tightness, dyspnoea, and lower abdominal distension. Echocardiography revealed a mass in the right atrium. An emergency operation was carried out to prevent tumour shedding. The patient was discharged on the 4th day of tumour resection, without any complications At the 18 months follow-up, she suffered from kidney and lung tumours. She refused any treatment and passed away. scRNA-seq was applied to analyse the nature of the tumour. The cellular components of benign tumours include chondrocytes, smooth muscle cells, fibroblasts, mesenchymal stromal cells, and osteoblasts. Additionally, the cyclic guanosine monophosphate (cGMP-PKG) signalling pathway, transcriptional misregulation in cancer, and the p53 signalling pathway may be related to the growth of this tumour. scRNA-seq is a good approach to analyse growth patterns of cardiac tumours and helpful for distinguishing the nature of the tumour.

Spatial distribution and quantitative source identification of nutrients and beneficial elements in the soil of a typical suburban area, Beijing.

Source identification and quality monitoring of soil nutrients and beneficial elements (NBEs) are crucial for agricultural production and environmental protection. In this study, grid sampling (223 topsoil samples and 223 subsoil samples) was carried out in the Tongzhou District of Beijing. The concentration level of representative NBEs (N, P, K, Ca, Mg, Se, V, Ge, Mn, Zn) and some typical soil properties representing indicators (total organic carbon, TFe2O3, Al2O3/SiO2, and pH) in soils and their spatial distribution were analyzed. The major sources contributing to these NBEs were assessed by principal component analysis (PCA), redundancy analysis (RDA), and positive matrix factorization (PMF) analysis. The results suggested that the soil parent material contributed 40.09-69.84% to Zn, V, Ge, Mn, F, and K in soils; the local external source contributed 54.89-75.04% to N, Se, and TOC; and the hydrous system contributed 40.67-77.31% to Ca and Mg. The enrichment degree of each NBE was calculated using the standardized concentration ratio method. These indices exhibited the influence and mixing process of different sources on the target NBEs in topsoils. The individual concentrations of the target NBEs and the combined concentrations of N, P, and K were used to evaluate the soil quality. Our study estimated the relative contributions from dominant sources to NBEs in soils from a typical suburban area, providing a basis for agricultural activities and environmental protection.

A Novel Inflammation-Based Risk Score Predicts Mortality in Acute Type A Aortic Dissection Surgery: The Additive Anti-inflammatory Action for Aortopathy and Arteriopathy Score.

Objective: To develop an inflammation-based risk stratification tool for operative mortality in patients with acute type A aortic dissection. Methods: Between January 1, 2016 and December 31, 2021, 3124 patients from Beijing Anzhen Hospital were included for derivation, 571 patients from the same hospital were included for internal validation, and 1319 patients from other 12 hospitals were included for external validation. The primary outcome was operative mortality according to the Society of Thoracic Surgeons criteria. Least absolute shrinkage and selection operator regression were used to identify clinical risk factors. A model was developed using different machine learning algorithms. The performance of the model was determined using the area under the receiver operating characteristic curve (AUC) for discrimination, calibration curves, and Brier score for calibration. The final model (5A score) was tested with respect to the existing clinical scores. Results: Extreme gradient boosting was selected for model training (5A score) using 12 variables for prediction-the ratio of platelet to leukocyte count, creatinine level, age, hemoglobin level, prior cardiac surgery, extent of dissection extension, cerebral perfusion, aortic regurgitation, sex, pericardial effusion, shock, and coronary perfusion-which yields the highest AUC (0.873 [95% confidence interval (CI) 0.845-0.901]). The AUC of 5A score was 0.875 (95% CI 0.814-0.936), 0.845 (95% CI 0.811-0.878), and 0.852 (95% CI 0.821-0.883) in the internal, external, and total cohort, respectively, which outperformed the best existing risk score (German Registry for Acute Type A Aortic Dissection score AUC 0.709 [95% CI 0.669-0.749]). Conclusion: The 5A score is a novel, internally and externally validated inflammation-based tool for risk stratification of patients before surgical repair, potentially advancing individualized treatment. Trial Registration: clinicaltrials.gov Identifier: NCT04918108.

[Levels of tPSA and fPSA and count of peripheral blood neutrophils in the diagnosis of prostate cancer].

OBJECTIVE: To investigate the value of combined detection of tPSA, fPSA and peripheral blood neutrophil count (Neut#) in the diagnosis of PCa. METHODS: This study included 238 cases of PCa, 328 cases of BPH and 303 normal men as healthy controls present at our hospital for medical or physical examination from August 2018 to December 2021. We detected the levels of serum tPSA and fPSA and Neut# of the subjects, and assessed the value of the combined detection in the diagnosis of PCa using logistic regression analysis, ROC curves, Pearman correlation analysis and nonparametric test. RESULTS: There were significant differences in the tPSA and fPSA levels and Neut# between any two of the PCa, BPH and healthy control groups (P < 0.05). The index N of the combined detection of tPSA, fPSA and Neut# showed an evidently higher diagnostic value than that of any single-item detection. The Gleason scores of the subjects were correlated positively with the tPSA and fPSA levels and index N, with the correlation coefficients of 0.184, 0.245 and 0.166 respectively, P < 0.05), and negatively with the Neut#, with the correlation coefficient of －0.168, P < 0.05). Statistically significant differences were observed in the tPSA and fPSA levels, Neut# and index N in those with different Gleason scores (P < 0.05). CONCLUSION: The combined detection of tPSA, fPSA and Neut# improves the diagnosis of PCa and can be applied clinically as an auxiliary diagnostic method.

Circulating biomarker-based risk stratifications individualize arch repair strategy of acute Type A aortic dissection via the XGBoosting algorithm.

Aims: The incremental usefulness of circulating biomarkers from different pathological pathways for predicting mortality has not been evaluated in acute Type A aortic dissection (ATAAD) patients. We aim to develop a risk prediction model and investigate the impact of arch repair strategy on mortality based on distinct risk stratifications. Methods and results: A total of 3771 ATAAD patients who underwent aortic surgery retrospectively included were randomly divided into training and testing cohorts at a ratio of 7:3 for the development and validation of the risk model based on multiple circulating biomarkers and conventional clinical factors. Extreme gradient boosting was used to generate the risk models. Subgroup analyses were performed by risk stratifications (low vs. middle-high risk) and arch repair strategies (proximal vs. extensive arch repair). Addition of multiple biomarkers to a model with conventional factors fitted an ABC risk model consisting of platelet-leucocyte ratio, mean arterial pressure, albumin, age, creatinine, creatine kinase-MB, haemoglobin, lactate, left ventricular end-diastolic dimension, urea nitrogen, and aspartate aminotransferase, with adequate discrimination ability {area under the receiver operating characteristic curve (AUROC): 0.930 [95% confidence interval (CI) 0.906-0.954] and 0.954, 95% CI (0.930-0.977) in the derivation and validation cohort, respectively}. Compared with proximal arch repair, the extensive repair was associated with similar mortality risk among patients at low risk [odds ratio (OR) 1.838, 95% CI (0.559-6.038); P = 0.316], but associated with higher mortality risk among patients at middle-high risk [OR 2.007, 95% CI (1.460-2.757); P < 0.0001]. Conclusion: In ATAAD patients, the simultaneous addition of circulating biomarkers of inflammatory, cardiac, hepatic, renal, and metabolic abnormalities substantially improved risk stratification and individualized arch repair strategy.

Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma.

We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.

[Alternating magnetic field damages the reproductive function of murine testes].

OBJECTIVE: To explore the relationship between physical and biological effects of alternating magnetic field and study the influence of the magnetic field on the reproductive function of murine testes. METHODS: Thirty ICR mice were randomized into 5 groups: normal control, X-ray radiation, weak magnetic field (1000 Hz), 1 h strong magnetic field and 2 h strong magnetic field (2000 Hz). The mice were sacrificed at 7 days after the exposure for the analysis of testicular sperm motility, observation of histopathological changes in the testis by HE staining and evaluation of the changes by modified Johnsen grade criteria. RESULTS: The rates of sperm motility were (42.37 +/- 10.24)% in the normal control group, (39.00 +/- 12.35)% in the X-ray radiation group, (36.00 +/- 17.28)% in the weak magnetic field group, (10.72 +/- 5.67)% in the 1 h strong magnetic field group and (4.44 +/- 2.87)% in the 2 h strong magnetic field group, respectively. Johnsen's scores decreased and the testis damage increased in a dose- and time-dependent manner. CONCLUSION: Magnetic field, either strong or weak, may damage the testis function by inducing injury to seminiferous tubules and Leydig cells, thickening of the basal membrane, derangement, exfoliation, massive apoptosis and necrosis of spermatogenic cells in the lumen, situation of the epididymis, and consequently the absence of sperm.

[Study on the differential expression of lipid metabolism-related genes in young LDLR knockout mice liver].

OBJECTIVE: To clarify the differential expression of the genes related to the lipid metabolism in the early stage of atherosclerosis in the young LDLR-/- mice of different ages. METHODS: A RT-PCR assay was used to analyse the gene expression patterns in the livers of LDLR-/- mice and wild type (WT) mice from 14 to 90 days. The characteristics of early lipid deposition in intima were evaluated using biochemical and pathological techniques. RESULTS: In LDLR-/- mice, when compared to WT mice, the mRNA level of the apolipoprotein A IV (apoA IV), fatty acid translocase (Fat/CD36) and carnitine palmitoyl transferase I (CPT I) changed prominently at the age of 14-days (P < 0.05). At 30 days, the mRNA level of apolipoprotein A I (apoA I) was up regulated, but apolipoprotein F (apoF), CD36 and CPT I were down regulated (P < 0.05). At 60 days, the mRNA levels of apoA I, CPT I and liver X receptor alpha (LXRalpha) were up regulated, but apoA IV was down regulated (P < 0.05). At 90 days, the level of the apoA I was higher, but the expression of the apoA IV, apoF and acyl-coenzymeA oxidase 1 (ACOX1) were down regulated (P < 0.05), whereas the expression of apolipoprotein A V (apoA V), apolipoprotein E (apoE), peroxidase proliferator-activated receptor alpha (PPARalpha) and angiopoietin-like protein 3 (angptl 3) had no significant changes (P > 0.05). The serum levels of TC (P < 0.05), TG (P < 0.05) and LDLC (P < 0.05) in LDLR-/- mice were significantly higher than those in wild type mice with the same age. CONCLUSIONS: The mRNA levels of the apoA I, apoA IV, apoF, FAT/CD36, CPT I, ACOX1 and LXRalpha of the LDLR-/- mice were significantly changed compared to the WT mice. The genes may be of some relevance to the complicated lipid metabolism network, and have effect in the early stage of atherogenesis.

[Differential expressions of lipid metabolism related genes in the liver of young apoE knockout mice].

The work was aimed to investigate the differential expressions of lipid metabolism related genes in the early stage of atherosclerosis in the young apolipoprotein E deficient (apoE(-/-)) mice at different ages with normal chow diet. The genotypes of mice were identified by using multiplex polymerase chain reaction (multi-PCR) analysis. The semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR were used to analyze the expressions of lipid metabolism related genes in the liver of apoE(-/-) and age-matched wild type (WT) mice of 14-day old, 1-month old, 2-month old, 3-month old. The serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) contents were assayed using COD-PAP and GPO-PAP methods. The serum apolipoprotein B100 (apoB100) content was quantitated by immune turbidimetry. The hearts were perfusion-fixed in 4% formaldehyde, infiltrated with 30% gum sucrose for 24 h at 4 °C, and embedded in OCT compound. The aortic sinus tissues were serially sectioned at -15 °C, stained with Sudan IV, and counterstained with light green. The results were shown as follows. Compared with that in WT mice, the mRNA levels of apoA I and apoA IV in apoE(-/-) mice aged from 14-day old to 3-month old changed prominently (P<0.05), with apoA I up-regulated and apoA IV down-regulated. At the age of 1 month, the expression of apoB100 in apoE(-/-) mice was higher than that in WT mice (P<0.05). The expression of apoA V was up-regulated (P<0.05) and there was obvious lipid deposition in the aortic intima in apoE(-/-) mice at the age of 2 months. The expressions of fatty acid translocase (Fat/CD36) and angiopoietin-like protein 3 (Angptl 3) in apoE(-/-) mice were higher than those in WT mice at the age of 3 months (P<0.05), while the expressions of peroxisome proliferator-activated receptor α (PPARα), liver X receptor α (LXRα), carnitine palmitoyl transferase I (CPT I) and acyl coenzyme A oxidase 1 (ACOX1) showed no significant changes. The serum TC, TG, LDL-C and HDL-C contents in apoE(-/-) mice aged from 14-day old to 3-month old were higher than those in age-matched WT mice. apoE(-/-) mice showed a marked increase in serum apoB100 content, consistent with the trend of serum LDL-C content and apoB100 mRNA content in the liver. The results suggest that the mRNA expressions of apoA I, apoA IV, apoA V, apoB100 and Angptl 3 in apoE(-/-) mice change significantly compared with those in WT mice, and these genes might be relevant to the complicated lipid metabolism network, and involved in the early stage of atherogenesis.

[Pharmacokinetics and bioequivalence of eperisone hydrochloride tablet in healthy subjects].

AIM: To develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human. METHODS: Buflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer. RESULTS: Calibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%. CONCLUSION: The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.

[Bioequivalence of donepezil capsule and tablet in human].

AIM: To develop an HPLC-MS assay for determination of donepezil in human plasma and to investigate the pharmacokinetics and bioequivalence of donepezil capsule in healthy volunteers. METHODS: A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 5 mg dose of either capsule or tablet was administered to each volunteer. After spiked with the internal standard (phenoprolamine) and treated with saturated sodium bicarbonate, plasma was extracted with ethyl acetate and separated with a C18 reversed phase column. LC-ESIMS was used in the selected ion monitoring (SIM) mode with target ions at m/z 380 for donepezil and m/z 344 for phenoprolamine. The fragmentor voltage was 120 V. The main pharmacokinetic parameters of donepezil and the bioequivalence of its two preparations were calculated. RESULTS: The main pharmacokinetic parameters T1/2, Tmax and Cmax were (63 +/- 10) h, (3.3 +/- 0.4) h and (8.5 +/- 0.4) microgram.L-1 for the capsule; (57 +/- 9) h, (3.4 +/- 1.0) h and (8.1 +/- 1.0) microgram.L-1 for the tablet, respectively. The relative bioavailability of the donepezil capsule was 102% +/- 11%. CONCLUSION: The assay was shown to be sensitive, accurate and convenient. The two preparations of donepezil were bioequivalent.