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Biomedical subjects

Bo Yu

Publications and source records attributed to Bo Yu.

At least 19 recordsLinked to original sources

Efficient genome editing in tomato using Cas12i3 variants.

Systematic comparison of Cas12i gene-editing tools in tomato identifies Cas-SF01 as the most efficient variant, achieving editing efficiencies comparable to conventional Cas9 at some genomic sites and providing a compact, highly specific, and versatile tool for studying gene function, engineering fruit metabolism, and developing improved tomato varieties through precision breeding.

Journal Article↗

Single-center experience with isolated male epispadias: Outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs by anatomical subtype.

BACKGROUND: Isolated male epispadias (IME) is a rare congenital malformation. Surgical repair aims to improve urinary function, correct penile curvature, reconstruct the urethra and glans, and preserve future sexual function. Because available series are small, the influence of anatomical subtype and operative technique on outcome remains incompletely defined. OBJECTIVE: To report single-center outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs for IME, with attention to anatomical subtype, complications, and age-appropriate continence outcomes. METHODS: We retrospectively reviewed boys with IME who underwent primary urethral reconstruction in my hospital, Capital Medical University, from May 2005 to June 2024. Data were locked on 30 June 2024. Primary outcomes were postoperative complications graded by the Clavien-Dindo system and urinary continence at last follow-up in patients aged 5 years or older. Secondary outcomes included improvement of preoperative incontinence, ICIQ score, subsequent bladder neck reconstruction, penile appearance/residual curvature when documented, and patient/parent-reported sexual function. RESULTS: Sixty-seven patients were included: 35 underwent modified Cantwell-Ransley repair and 32 underwent Thiersch-Duplay repair. The cohort included 26 glanular (38.8%), 23 penile (34.3%), and 18 penopubic (26.9%) cases. Median age at surgery was 28 months in both groups. Median age at last follow-up was 92.8 months (IQR 63.9-108.4) after modified Cantwell-Ransley repair and 137.9 months (IQR 77.9-172.6) after Thiersch-Duplay repair (P = 0.011). Procedure distribution differed by meatal location (P = 0.036), although penopubic cases were treated with both procedures. Total complications occurred in 5/35 and 5/32 patients, respectively. Formal continence analysis included 26 modified Cantwell-Ransley patients and 27 Thiersch-Duplay patients aged 5 years or older. Postoperative urinary incontinence persisted in 14/26 (53.8%) and 12/27 (44.4%), respectively. Among age-eligible patients with preoperative incontinence, any improvement was documented in 13/20 (65.0%) and 14/17 (82.4%), and complete remission occurred in 6/20 (30.0%) and 5/17 (29.4%), respectively. Three patients, all with penopubic epispadias treated with Thiersch-Duplay repair, subsequently underwent bladder neck reconstruction for persistent incontinence. Erectile function data were available in 37/67 patients (55.2%). CONCLUSIONS: In this large single-center retrospective cohort, Thiersch-Duplay and modified Cantwell-Ransley repairs had comparable overall complication rates. Continence and reoperation patterns were strongly influenced by anatomical subtype, with penopubic epispadias representing the highest-risk group. These findings support individualized, anatomy-conscious operative planning and prospective evaluation of standardized selection criteria, rather than a single prescriptive algorithm. CLINICAL/TRANSLATIONAL IMPLICATION: This series supports standardized reporting of anatomical subtype, age-appropriate continence outcomes, and graded complications when counseling families and comparing outcomes across centers. LEVEL OF EVIDENCE: Level III.

Humans↗

Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes.

BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into cardiomyocytes if an appropriate cellular environment is provided. Notch signals exchanged between neighboring cells through the Notch receptor can eventually dictate cell differentiation. In our study, we show that MSC differentiation into cardiomyocytes is dependent on the Notch signal. METHODS: We created a myocardial infarction model in rat by coronary ligation, administered direct intramyocardial injection of DAPI-labeled MSC immediately, and observed the differentiation of MSCs after 14 days by immunofluorescence staining against troponin T. We cultured MSCs and cardiomyocytes in four ways, respectively, in vitro. (1) MSCs cocultured with cardiomyocytes obtained from neonatal rat ventricles in a ratio of 1:10. (2) The two types of cells were cultured in two chambers separated by a semipermeable membrane as indirect coculture group. (3) Notch receptor-soluble jagged1 protein was added to indirect coculture group. (4) Both jagged1 protein and gamma-secretase inhibitor-DAPT were added to indirect coculture group. Two weeks later, we observed the differentiation percentage, respectively, by immunofluorescence staining. RESULTS: We found the differentiation of MSCs which were close to cardiomyocytes in vivo. The differentiation percentage of the four cell culture group was 30.13+/-2.16%, 12.52+/-1.18%, 26.33+/-2.20%, and 13.08+/-1.15%. CONCLUSIONS: MSCs can differentiate into cardiomyocytes in vitro and in vivo if a cardiomyocyte microenvironment is provided. 2. Cell-to-cell interaction is very important for the differentiation of MSCs into cardiomyocytes. 3. Jagged1 protein can activate Notch signal and enhance the differentiation of MSC into cardiomyocyte, while the effect can be inhibited by DAPT.

Animals↗

Microbial desulfurization of gasoline by free whole-cells of Rhodococcus erythropolis XP.

Rhodococcus erythropolis XP could grow well with condensed thiophenes, mono-thiophenic compounds and mercaptans present in gasoline. Rhodococcus erythropolis XP was also capable of efficiently degrading the condensed thiophenes in resting cell as well as biphasic reactions in which n-octane served as a model oil phase. Free whole cells of R. erythropolis XP were adopted to desulfurize fluid catalytic cracking (FCC) and straight-run (SR) gasoline oils. About 30% of the sulfur content of FCC gasoline and 85% of sulfur in SR gasoline were reduced, respectively. Gas chromatography analysis with atomic emission detection also showed depletion of sulfur compounds in SR gasoline. Rhodococcus erythropolis XP could partly resist the toxicity of gasoline and had an application potential to biodesulfurization of gasoline.

Biodegradation, Environmental↗

Deep desulfurization of diesel oil and crude oils by a newly isolated Rhodococcus erythropolis strain.

The soil-isolated strain XP was identified as Rhodococcus erythropolis. R. erythropolis XP could efficiently desulfurize benzonaphthothiophene, a complicated model sulfur compound that exists in crude oil. The desulfurization product of benzonaphthothiophene was identified as alpha-hydroxy-beta-phenyl-naphthalene. Resting cells could desulfurize diesel oil (total organic sulfur, 259 ppm) after hydrodesulfurization. The sulfur content of diesel oil was reduced by 94.5% by using the resting cell biocatalyst for 24 h at 30 degrees C. Biodesulfurization of crude oils was also investigated. After 72 h of treatment at 30 degrees C, 62.3% of the total sulfur content in Fushun crude oil (initial total sulfur content, 3,210 ppm) and 47.2% of that in Sudanese crude oil (initial total sulfur, 1,237 ppm) were removed. Gas chromatography with pulsed-flame photometric detector analysis was used to evaluate the effect of R. erythropolis XP treatment on the sulfur content in Fushun crude oil, and it was shown that most organic sulfur compounds were eliminated after biodesulfurization.

Gasoline↗

Selective biodegradation of S and N heterocycles by a recombinant Rhodococcus erythropolis strain containing carbazole dioxygenase.

The carbazole dioxygenase genes were introduced into a dibenzothiophene degrader. The recombinant Rhodococcus erythropolis SN8 was capable of efficiently degrading dibenzothiophene and carbazole simultaneously. SN8 could also degrade various alkylated derivatives of carbazole and dibenzothiophene in FS4800 crude oil by just a one-step bioprocess.

Biodegradation, Environmental↗

[Alternations of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kidney ischemic Injury].

OBJECTIVE: To study the changes of ADF and G-actin in renal tubular epithelial cell of neonatal rats during kindney ischemic injury. To explore the interactions between ADF and G-actin and their relationships with actin cytoskeleton. METHODS: Twenty-four neonatal rats were used to the experiments due to have the weights from 30 to 40 g respectively. Renal ischemia was induced by clamping the left renal pedicle for different periods of time that was in 10 min or 30 min. The kidneys of normal neonatal rats were functioned as the control group. Two kinds of primary antibodies, which one was rabbit anti-chick ADF antiserum and another was mouse monoclonal G-actin antibody, were used on one same section of kidney tissue. FITC-labeled and TRITC-labeled secondary antibodies were used to identify ADF and G-actin respectively. These samples were examined by using a fluorescene microscope. RESULTS: In control group, ADF and G-actin showed to be diffused in cytoplasm of renal tubular epithelial cell. In ischemic injury group, the distributions of ADF and G-actin were changed significantly to apical region of tubular epithelial cells and the renal tubula lumen. Regardless of the ADF expression to not change but G-actin was increased after kidney ischemia. CONCLUSION: Under the physiolgical condition, ADF and G-actin got a diffuse distribution in cytoplasm of renal tubular epitbelial cell. However, when the kidney got in ischemia, the distributions of ADF and G-actin were changed significantly to apica region of tubular epithelial cell or the renal tubular lumen.

Actin Depolymerizing Factors↗

[Analysis of 618 cases of radical resection of rectal carcinoma].

OBJECTIVE: To investigate and analyse curative effects of Miles operation and anal sphincter preserving operation for rectal carcinoma in 20 years. METHODS: From 1984 to 2004, 618 cases of rectal carcinoma that underwent radical resection including Miles operation and anal sphincter preserving procedures were analysed retrospectively each 10 years, earlier 10 years from 1984 to 1994, and later 10 years from 1994 to 2004. RESULTS: Among the 618 cases, 492 (79.6%) were followed up. The median of the follow-up time was 5.4 years. In the earlier 10 years, local recurrence rate of post operation was 6.9% (14/201), for Miles operation and anal sphincter preserving procedures the local recurrence rate was 6.7% and 7.1% respectively. In the later 10 years, the local recurrence rate was 5.1% (15/291), 4.8% for Miles operation, 5.2% for anal sphincter preserving procedures. With the procedure of canular anastomosis of colon and rectal mucosa, the local recurrence rate was 4.9%. Overall five-year survival rate was 64.7% (130/201) in the earlier 10 years, 66.3% (59/89) for Miles operation, 63.4% (71/112) for anal sphincter preserving procedures. In the later 10 years, the five-year survival rate was 68.0% (198/291) in all, for Miles operation 66.3% (55/83), for anal sphincter preserving procedures 68.7% (143/208). With the procedure of canular anastomosis of colon and rectal mucosa, the five-year survival rate was 71.3% (62/87). CONCLUSIONS: The operation for rectal cancer should be chosen individually according to locus, biological character, and clinical stages. Anal sphincter preserving procedures are performed increasingly, and they provide the same five-year survival rate as Miles operation does, and the patient's quality of life can be improved obviously.

Adult↗

[Expression of metallothionein and FasL in colorectal cancer and its clinical significance].

OBJECTIVE: To study the expression of metallothionein (MT) and FasL in colorectal cancer and their relation to lymph node and liver metastasis. METHODS: Immunohistochemistry and quantitative RT-PCR were used to detect expression of MT and FasL in protein and mRNA levels in 93 cases of colorectal cancer. RESULTS: The rates of MT expression in primary foci, non-cancerous colon mucosa, lymph node metastasis and liver metastasis were 58.1%, 32.3%, 81.1%, 64.3% respectively. And the rates of FasL expression were 41.9%, 19.4%, 62.3%, and 92.9% respectively. The positive rates of MT and FasL in primary foci, liver and lymph node metastasis were higher than that in non-cancerous mucosa (chi(2) = 35.2421, 57.5152, P < 0.01). MT expression rate in lymph node metastasis was higher than that in primary foci (chi(2) = 8.0565, P < 0.01). In liver metastasis, FasL expression rate was higher than in lymph node metastasis and primary foci (chi(2) = 8.6674, 22.4455, P < 0.01). The positive rates of MT and FasL in Dukes stage C and D were higher than that in Dukes stage A and B (chi(2) = 18.8871, 25.1650, P < 0.01). And higher rates of MT and FasL expression were observed in low differentiation adenocarcinoma and mucus adenocarcinoma than in middle-high differentiation adenocarcinoma (chi(2) = 11.1546, 9.2239, P < 0.05). High MT mRNA level was found in lymph node metastasis and high FasL mRNA level in liver metastasis. CONCLUSIONS: Enhanced expression of MT and FasL was associated significantly with lymph node and liver metastasis of colorectal cancer. Assay of MT and FasL expression has prognostic values for colorectal cancer patients.

Adult↗

Mechanism of persistent ischemic mitral regurgitation after annuloplasty: importance of augmented posterior mitral leaflet tethering.

BACKGROUND: We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated. METHODS AND RESULTS: In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001). CONCLUSIONS: Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.

Aged↗

[Proteome study of colorectal cancer genesis and hepatic metastasis].

OBJECTIVE: To study differential proteins and their biological functions associated with colorectal cancer genesis and hepatic metastasis by proteomics and molecular biology techniques. METHODS: Isoelectric focusing/SDS acrylamide gel two-dimensional electrophoresis was used to analyse the expression of differential proteins from normal colorectal mucosa, primary cancer lesion and hepatic metastasis region. Liquid chromatography/mass spectrometry (LC-MS/MS) was used to identify the differential proteins. Transfection of colorectal cancer lovo cells was performed with the differential protein cDNA, and the changes of cell biological behavior was observed. RESULTS: Significant difference in protein expression was found on two-dimensional electrophoresis. Thirteen differential protein spots were analysed and identified. Human carbonic anhydrase II was detected in normal colorectal mucosa but not in primary cancer lesion and hepatic metastasisnegion. Phosphoglycerate kinase 1, fumarate hydratase and aldolase A were expressed in primary cancer. Expression of homo sapiens arginase and homo sapiens glutathione S-transferase A3 was found in hepatic metastasisnegion, but not in primary cancer lesion. After transfection with human carbonic anhydrase II cDNA, the lovo cells changed obviously with reduction in invasiveness, chemotaxy motor ability and tolerance. CONCLUSION: Differential expression of proteins was found between colorectal cancer genesis and hepatic metastasisnegion. No carbonic anhydrase II expression and enhanced expression of sapiens arginase and sapiens glutathione S-transferase A3 are related with biological behavior of colorectal cancer cell and facilitate hepatic metastasis.

Adult↗

Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients with localized basal inferior left ventricular remodeling: insights from tissue Doppler strain imaging.

OBJECTIVES: The purpose of this research was to test whether papillary muscle (PM) dysfunction attenuates ischemic mitral regurgitation (MR) in patients with left ventricular (LV) remodeling of a similar location and extent. BACKGROUND: Papillary muscle dysfunction could attenuate tethering and MR because of PM elongation. However, variability in the associated LV remodeling, which exaggerates tethering, can influence the relationship between PM dysfunction and MR. METHODS: In 40 patients with a previous inferior myocardial infarction but without other lesions, the LV volume, sphericity, PM tethering distance, PM longitudinal systolic strain, and MR fraction were quantified by echocardiography. The patients were divided into two groups: group 1 with significant basal inferoposterior LV bulging but without advanced LV bulging involving other territories, therefore with a similar location and extent of LV remodeling, and group 2 without significant LV bulging. RESULTS: The medial PM tethering distance was significantly correlated with the %MR fraction (r2 = 0.64, p < 0.01), and multiple regression analysis identified an increase in the tethering distance as the only independent determinant of the MR fraction in all subjects and also in group 1. The PM longitudinal systolic strain had no significant relationships with MR fraction in all subjects with variable degrees of LV remodeling, but it had a significant inverse correlation with the MR fraction (r2 = 0.33, p < 0.01) in group 1 with LV remodeling of a similar location and extent, indicating that PM dysfunction is associated with less MR. CONCLUSIONS: Papillary muscle dysfunction, reducing its longitudinal contraction to induce leaflet tethering, attenuates ischemic MR in patients with basal inferior LV remodeling.

Aged↗

Combined liposome-mediated cytosine deaminase gene therapy with radiation in killing rectal cancer cells and xenografts in athymic mice.

PURPOSE: The aim of this study was to assess the antitumor efficacy of combination of cytosine deaminase (CD) suicide gene therapy with radiation and to grope for new therapeutic strategy for local recurrent rectal cancer. EXPERIMENTAL DESIGN: HR-8348 cell line of human rectal cancer was used to assess efficiency of transfection with plasmid pEGFP-N1 and PXJ41-CD. The cells were exposed to radiation followed by liposome-mediated transfection. Cell inhibition assay was done with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Antitumor efficacy of combined liposome-mediated CD suicide gene therapy with radiation was determined by treatment of nude mice bearing HR-8348 cancer cell xenograft. RESULTS: The efficiency of liposome-mediated CD gene transfection can be improved by radiation. With radiation at 2, 4, 6, and 8 Gy, the efficiency of liposome-mediated transfection increased from 21.3% to 62.2%, 78.0%, 83.2%, and 87.8%, respectively. CD expression was enhanced as well. Cancer cell inhibition experiment showed that combined liposome-mediated CD gene therapy with radiation had much stronger antitumor effect. With HR-8348 tumor xenograft model, suppression of tumor xenograft was observed. Compared with control group, tumor volume was inhibited by 81.5%, 48.5%, and 37.4%, respectively, in the combined CD/5-fluorocytosine with radiation group, CD/5-fluorocytosine group, and radiation group and the wet weight of tumor was decreased by 80%, 41.7%, and 37.7%, respectively. CONCLUSION: These findings suggested that combination of liposome-mediated CD gene therapy with radiation is a safer and efficient anticancer method. Its therapeutic efficacy may meet clinical treatment on local recurrent rectal cancer.

Animals↗

Donepezil blocks voltage-gated ion channels in rat dissociated hippocampal neurons.

Donepezil (E2020) is a novel cholinesterase inhibitor for the treatment of Alzheimer's disease. Recent studies show that it may act on targets other than acetylcholinesterase in the brain. In the present study, the actions of donepezil on voltage-gated Na+ and K+ channels were investigated in rat dissociated hippocampal neurons. Donepezil reversibly inhibited voltage-activated Na+ current (I(Na)), delayed rectifier K+ current (I(K)) and fast transient K+ current (I(A)). The inhibition of donepezil on I(Na) was dependent on the holding potential. When neurons were held at -100, -80 and -60 mV, the IC50 value was 436+/-19, 291+/-26 and 3.8+/-0.3 microM, respectively. The drug did not affect the activation, fast inactivation of I(Na) and its recovery from fast inactivation. The inhibition of donepezil on I(K) (IC50=78+/-5 microM) was voltage-dependent, whereas that on I(A) (IC50=249+/-25 microM) was voltage-independent. Donepezil caused a significant hyperpolarizing shift of the voltage-dependence of the activation and steady-state inactivation of I(K), without affecting the kinetic properties of I(A). Due to the high concentrations used, the blocking effects of donepezil on the voltage-gated ion channels are unlikely to contribute to the clinical benefits in patients with Alzheimer's disease.

Animals↗

Studies on the effectiveness of NaFeEDTA-fortified soy sauce in controlling iron deficiency: a population-based intervention trial.

The objective of this research was to study the effectiveness of NaFeEDTA-fortified soy sauce for controlling iron deficiency in a high-risk population. This was an 18-month, randomized, placebo-controlled intervention trial in 14,000 residents aged three years or older in Bijie City, Guizhou Province, China, using sodium-iron ethylene diamine tetraacetate (NaFeEDTA)-fortified soy sauce (29.6 mg Fe/100 ml). The study data included measurements of food consumption, hemoglobin, serum ferritin, and serum retinol. The results showed that the diet consisted primarily of cereals, fruits, and vegetables, with very little meat. Food consumption remained unchanged during the study period and was similar in the fortified and control groups. The average daily soy sauce consumption of the group consuming the fortified product was 16.4 ml per person, which provided 4.9 mg of iron from NaFeEDTA. At the end of the trial, all age and sex subgroups receiving NaFeEDTA had significantly higher hemoglobin levels, a lower prevalence of anemia, and higher plasma ferritin levels than the controls. The effects became statistically significant after six months of intervention and were maintained throughout the study period. We conclude that NaFeEDTA-fortified soy sauce was highly effective in controlling iron deficiency and reducing the prevalence of iron-deficiency anemia in men, women, and children. NaFeEDTA-fortified soy sauce is affordable and was well accepted by the study population.

Adolescent↗

Repeated sauna therapy increases arterial endothelial nitric oxide synthase expression and nitric oxide production in cardiomyopathic hamsters.

BACKGROUND: Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. METHODS AND RESULTS: Normal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39 degrees C followed by 20 min at 30 degrees C. This procedure raised the rectal temperatures by about 1 degrees C. Arterial endothelial nitric oxide (NO) synthase (eNOS) mRNA and protein expressions were examined, and serum concentrations of nitrate were measured. The expression of eNOS mRNA in the aortas of normal controls did not change, whereas those of the TO-2 hamsters decreased with age. Four weeks of sauna therapy significantly increased eNOS mRNA expression in the aortas of TO-2 hamsters compared with those that did not undergo sauna therapy. Sauna therapy also upregulated aortic eNOS protein expression. Serum nitrate concentrations of the TO-2 hamsters were increased by 4 weeks of sauna therapy compared with those that did not undergo sauna. CONCLUSION: Repeated sauna therapy increases eNOS expression and NO production in cardiomyopathic hamsters with heart failure.

Animals↗

Prediction of prognosis in the UM-X7.1 hamster model of congestive heart failure using the Tei index.

BACKGROUND: Cardiac function is difficult to evaluate in small animal models of heart disease. The Doppler Tei index is a simple and non-invasive measure that can express global cardiac function even in small animal models of congestive heart failure. However, its ability to predict prognosis has not been evaluated. METHODS AND RESULTS: We tested the hypothesis that cardiac functional indices, such as the Tei index, can predict the prognosis of hamsters with cardiac dysfunction. The Tei index, defined as the sum of the isovolume contraction and relaxation time divided by ejection time, and the percent fractional shortening of the left ventricle was measured in 48 anesthetized male hamsters (19.7+/-0.4 weeks old) with cardiac dysfunction (UM-X7.1), using Doppler and 2-dimensional echocardiography. The hamsters were separated into 2 groups based on the median Tei index (0.50) and % fractional shortening (FS) (21%). Kaplan-Meier analysis determined the survival rates of the groups. Both the Tei index and %FS enabled significant distinction of better and poorer survival (p < 0.01), and the survival curves were less overlapped when the animals were separated according to the Tei index. CONCLUSION: The Tei index can predict prognosis in a small animal model of heart failure.

Animals↗