Deep learning methods for diagnosis of graves' ophthalmopathy using magnetic resonance imaging.

Background: The effect of diagnosing Graves' ophthalmopathy (GO) through traditional measurement and observation in medical imaging is not ideal. This study aimed to develop and validate deep learning (DL) models that could be applied to the diagnosis of GO based on magnetic resonance imaging (MRI) and compare them to traditional measurement and judgment of radiologists. Methods: A total of 199 clinically verified consecutive GO patients and 145 normal controls undergoing MRI were retrospectively recruited, of whom 240 were randomly assigned to the training group and 104 to the validation group. Areas of superior, inferior, medial, and lateral rectus muscles and all rectus muscles on coronal planes were calculated respectively. Logistic regression models based on areas of extraocular muscles were built to diagnose GO. The DL models named ResNet101 and Swin Transformer with T1-weighted MRI without contrast as input were used to diagnose GO and the results were compared to the radiologist's diagnosis only relying on MRI T1-weighted scans. Results: Areas on the coronal plane of each muscle in the GO group were significantly greater than those in the normal group. In the validation group, the areas under the curve (AUCs) of logistic regression models by superior, inferior, medial, and lateral rectus muscles and all muscles were 0.897 [95% confidence interval (CI): 0.833-0.949], 0.705 (95% CI: 0.598-0.804), 0.799 (95% CI: 0.712-0.876), 0.681 (95% CI: 0.567-0.776), and 0.905 (95% CI: 0.843-0.955). ResNet101 and Swin Transformer achieved AUCs of 0.986 (95% CI: 0.977-0.994) and 0.936 (95% CI: 0.912-0.957), respectively. The accuracy, sensitivity, and specificity of ResNet101 were 0.933, 0.979, and 0.869, respectively. The accuracy, sensitivity, and specificity of Swin Transformer were 0.851, 0.817, and 0.898, respectively. The ResNet101 model yielded higher AUC than models of all muscles and radiologists (0.986 vs. 0.905, 0.818; P<0.001). Conclusions: The DL models based on MRI T1-weighted scans could accurately diagnose GO, and the application of DL systems in MRI may improve radiologists' performance in diagnosing GO and early detection.

Production of a human iPSC line from an early-onset Parkinson's disease patient with a novel CHCHD2 gene truncated mutation.

CHCHD2 mutations have been reported to cause Parkinson's disease (PD) by a loss of function in mitochondria. Most reported mutations, however, were missense, which was not the perfect model for a study of haploinsufficiency. Here, a truncated mutation, CHCHD2 p.Pro53Alafs*38, was identified in one familial early-onset PD patient. We generated a human-induced pluripotent stem cell (iPSC) line WCHSCUi001-A from this patient. The generated iPSCs resembled human embryonic stem cells, expressed pluripotency markers, exhibited a normal karyotype and could be differentiated into three germ layers in vitro. This line will be valuable for investigating the disease mechanisms and screening candidate drugs.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.

Automatic phantom-less QCT system with high precision of BMD measurement for osteoporosis screening: Technique optimisation and clinical validation.

BACKGROUND: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle. OBJECTIVE: The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis. METHODS: A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system. RESULTS: BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r â€‹= â€‹0.99) showed strong linear correlation and Bland-Altman analysis (bias â€‹= â€‹3.0mg/cc) indicated little difference between the two methods. The precision result (CV â€‹= â€‹0.89%) represented good reproducibility of the new system. CONCLUSION: The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application. TRANSLATIONAL POTENTIAL STATEMENT: With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.

Cervical Alignment of Patients with Basilar Invagination: A Radiological Study.

OBJECTIVE: To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). METHODS: A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull-C2 /Skull-BV, Skull-C7 , C2 -C7 /BV-C7 wall angles, C0 -C2 /C0 -BV, C0 -C7 , C1 -C7 , and C2 -C7 /BV-C7 angles were measured in dynamic X-ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. RESULTS: The BI patients had a smaller C0 -C2 /C0 -BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2 -C7 /BV-C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2 -C7 /BV-C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = -0.371), extension (r = -0.429), and flexion (r = -0.648) positions among BI patients, as well as in extension position (r = -0.317) among control group. The BI patients presented smaller total ROMs in Skull-C2 /Skull-BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0 -C2 /C0 -BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0 -C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2 -C7 /BV-C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull-C2 /Skull-BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull-C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0 -C2 /C0 -BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull-C2 /Skull-BV (-5.2° ± 9.4° vs -7.3° ± 8.0°), C0 -C2 /C0 -BV (-3.2° ± 8.8° vs -7.7° ± 8.7°), and C0 -C7 angles (-33.2° ± 13.0° vs -52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2 -C7 /BV-C7 wall angle (-33.9° ± 14.8° vs -8.2° ± 15.1°). CONCLUSION: The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

A novel compound heterozygous COL4A4 mutation in a Chinese family with Alport syndrome: A care case report.

RATIONALE: Alport syndrome (AS) is an inherited progressive renal failure, characterized by kidney disease, hearing loss, and eye abnormalities. PATIENT CONCERNS: A 7-year-old male child was admitted for persistent microscopic hematuria and proteinuria. DIAGNOSES: Combined with clinical manifestations, laboratory testing, pathological changes of kidney and sequencing results, the patient was diagnosed as AS. INTERVENTIONS: The patient was treated with ACEI and tacrolimus drugs for 2 years, but continued to have hematuria and proteinuria. Thus, a genetic analysis was performed using next-generation sequencing in four affected members from the family. OUTCOMES: The findings revealed triple compound heterozygous mutation of COL4A4: three novel variations, c.1045C>T (p. R349X), c.3505+1G>A (splicing), and c.2165G>A (p. G722D). LESSONS: This study was novel in finding that a triple variant of the COL4A4 gene simultaneously in trans and in cis. The effects of multiple mutation sites and the type of gene mutation in AS were also underlined.

Prognostic value of anti-HBc quantification in hepatitis B virus related acute-on-chronic liver failure.

BACKGROUND AND AIM: It has been reported that serum quantification of anti-HBc (qAnti-HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Its implication in HBV-ACLF was evaluated in this study. METHODS: Baseline serum qAnti-HBc levels were retrospectively detected in HBV-ACLF and CHB patients using recently developed double-sandwich immunoassay. The association of qAnti-HBc level with clinical outcomes was evaluated by multiple logistic regression. Nomogram was adopted to formulate an algorithm incorporating qAnti-HBc for the prediction of survival in HBV-ACLF. The post-hospitalization of HBV-ACLF patients were followed-up for 1 year. RESULTS: Eighty-eight HBV-ACLF as training set, 80 HBV-ACLF as validation set and 216 CHB cases were included. Serum qAnti-HBc level was significantly higher in HBV-ACLF (4.95 ± 0.54 log10  IU/mL) than CHB patients (4.47 ± 0.84 log10  IU/mL) (P < 0.01). Among HBV-ACLF cases, both in training and validation set, patients with poor outcomes had lower qAnti-HBc level. Area under receiver operating characteristic curve of the novel qAnti-HBc inclusive model was 0.82, superior to 0.73 from model for end-stage liver disease scores (P = 0.018), which was confirmed in validation set. During follow-up, the qAnti-HBc level declined at month 3 and month 6, then plateaued at 3.84 log10  IU/mL. CONCLUSIONS: Serum qAnti-HBc level was associated with disease severity and might be served as a novel biomarker in the prediction of HBV-ACLF clinical outcomes. The underlying immunological mechanism warrants further investigation.

Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity.

BACKGROUND: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. METHODS: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). RESULTS: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. CONCLUSIONS: Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Targeting GPER1 to suppress autophagy as a male-specific therapeutic strategy for iron-induced striatal injury.

The functional outcome of intracerebral hemorrhage (ICH) in young male patients are poor than in premenopausal women. After ICH, ferrous iron accumulation causes a higher level of oxidative injury associated with autophagic cell death in striatum of male mice than in females. In rodent model of ferrous citrate (FC)-infusion that simulates iron accumulation after ICH, female endogenous estradiol (E2) suppresses autophagy via estrogen receptor α (ERα) and contributes to less injury severity. Moreover, E2 implantation diminished the FC-induced autophagic cell death and injury in males, whose ERα in the striatum is less than females. Since, no sex difference of ERß was observed in striatum, we delineated whether ERα and G-protein-coupled estrogen receptor 1 (GPER1) mediate the suppressions of FC-induced autophagy and oxidative injury by E2 in a sex-dimorphic manner. The results showed that the ratio of constitutive GPER1 to ERα in striatum is higher in males than in females. The GPER1 and ERα predominantly mediated suppressive effects of E2 on FC-induced autophagy in males and antioxidant effect of E2 in females, respectively. This finding opens the prospect of a male-specific therapeutic strategy targeting GPER1 for autophagy suppression in patients suffering from iron overload after hemorrhage.

A Cross-Domain Collaborative Filtering Algorithm Based on Feature Construction and Locally Weighted Linear Regression.

Cross-domain collaborative filtering (CDCF) solves the sparsity problem by transferring rating knowledge from auxiliary domains. Obviously, different auxiliary domains have different importance to the target domain. However, previous works cannot evaluate effectively the significance of different auxiliary domains. To overcome this drawback, we propose a cross-domain collaborative filtering algorithm based on Feature Construction and Locally Weighted Linear Regression (FCLWLR). We first construct features in different domains and use these features to represent different auxiliary domains. Thus the weight computation across different domains can be converted as the weight computation across different features. Then we combine the features in the target domain and in the auxiliary domains together and convert the cross-domain recommendation problem into a regression problem. Finally, we employ a Locally Weighted Linear Regression (LWLR) model to solve the regression problem. As LWLR is a nonparametric regression method, it can effectively avoid underfitting or overfitting problem occurring in parametric regression methods. We conduct extensive experiments to show that the proposed FCLWLR algorithm is effective in addressing the data sparsity problem by transferring the useful knowledge from the auxiliary domains, as compared to many state-of-the-art single-domain or cross-domain CF methods.

Rectangular illumination using a secondary optics with cylindrical lens for LED street light.

The illumination pattern of an LED street light is required to have a rectangular distribution at a divergence-angle ratio of 7:3 for economical illumination. Hence, research supplying a secondary optics with two cylindrical lenses was different from free-form curvature for rectangular illumination. The analytical solution for curvatures with different ratio rectangles solved this detail by light tracing and boundary conditions. Similarities between the experiments and the simulation for a single LED and a 9-LED module were analyzed by Normalized Cross Correlation (NCC), and the error rate was studied by the Root Mean Square (RMS). The tolerance of position must be kept under ± 0.2 mm in the x, y and z directions to ensure that the relative illumination is over 99%.

[Influence of mast cell function on the analgesic effect of acupuncture of "Zusanli" (ST 36) in rats].

OBJECTIVE: To investigate the role of mast cells in acupuncture analgesia in rats. METHODS: A total of 48 Sprague Dawley (SD) rats were divided into normal control, acupoinc Effect [("Zusanli"(ST 36)-acupuncture (Acu), non-acupoint (3 mm left to ST36), disodium cromoglycate (DSC, 0.02 gmL, for acupoint injection), normal saline (NS, for acupoint injection), DSC + Acu, NS-b+ Acu and DSC+contralach Center ral Acu groups, with 6 cases in each group. The latency of tail flick response to heat irradiation was used as the pain threshold. "Zusanli" (ST 36) was punctured with filiform needle and stimulated by lifting and thrusting the needle for 30 min. After sacrifice under anesthesia (1% embutal) c, tissues of T36 area were sampled, sliced (4 microm), and stained with Toluidine Blue for skin and Neutral Red for muscles. RESULTS: Compared with normal control group, the ratios of pain threshold increased significantly in all the 7 experimental groups (P < 0.05), and those of DSC and NS groups were significantly lower than those of acupoint-Acu, non-acupoint, DSC+ Acu, NS+ Acu and DSC + contralateral Acu groups (P < 0.05) n. Comp + Acu group, the ratios of NS+Acu and DSC+ contralateral Acu groups were evidently higher (P < 0.05, 0.01). Compared with control group, the degranulation ratio of acupoint-Acu group was significantly higher (P < 0.05, 0.001 in muscle and skin separately), and the ratio of DSC+ Acu group was markedly lower than that of acupoint-Acu group (P < 0.01 in skin). CONCLUSION: Acupuncture of ST36 has a significant analgesia and enhances the degranulation of mast apparently cells, which is weakened by injection of DSC in the acupoint area, suggesting an important role of mast cells in acupuncture-induced analgesia.

Angiotensin II induced cardiac hypertrophy is blocked by PTEN via suppressing Ca2+/Calcineurin pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of PTEN on Ang II induced cardiomyocyte hypertrophy and subsequent Ca(2+)/Calcineurin pathway changes.</p><p><b>METHODS</b>Primary cultured neonatal rat cardiomyocytes were cultured and were treated with phosphate-buffered saline, empty adenovirus (Ad-GFP), or adenovirus encoding for PTEN (Ad-PTEN-GFP) for 48 h and Ang II (10(-7) mol/L) was added to the medium for another 24 h. Cells were harvested and intracellular Ca(2+) concentration ([Ca(2+)] i) was determined by Fura-2/AM ratio imaging analysis; PTEN, ANF, beta-MHC and CaNAbeta mRNA evaluated with RT-PCR; PTEN and CaNAbeta protein by Western blot; CaN phosphatase activity by CaN detecting kits.</p><p><b>RESULTS</b>PTEN at mRNA and protein levels were significantly higher in Ad-PTEN-GFP treated cardiomyocytes than that of Ad-GFP treated cardiomyocytes. Ang II stimulation upregulated [Ca(2+)] i, CaNAbeta at mRNA and protein levels and CaN phosphatase activity in Ad-GFP treated cardiomyocytes but not in Ad-PTEN-GFP treated cardiomyocytes.</p><p><b>CONCLUSIONS</b>Cardiac hypertrophy induced by Ang II could be blocked by PTEN overexpression via suppressing Ca(2+)/Calcineurin pathway.</p>

The relationship between expressions of beta1-, beta2-, beta3-adrenoceptor mRNA of myocardium and cardiac function in patients with heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the alteration of expressions of beta(1)-, beta(2)-, beta(3)-adrenoceptor mRNA in human myocardial tissue and the relation between their expressions and cardiac function in patient with heart failure.</p><p><b>METHODS</b>The mRNA expressions of beta(1)-, beta(2)- and beta(3)-adrenergic receptors in myocardial tissue were analyzed by using the reverse transcriptase-polymerase chain reaction in 24 patients with heart failure of valvular heart disease and 5 control subjects.</p><p><b>RESULTS</b>Beta(1)-adrenergic receptor mRNA expressions in myocardium were significantly lower in patients with heart failure than those in control subjects, and progressively reduced with aggravation of heart function. By contrast, beta(3)-adrenoceptor mRNA expressions were significantly higher in patients with heart failure than those in controls, and progressively elevated with aggravation of cardiac function. No difference was observed in beta(2)-adrenergic receptor among all groups.</p><p><b>CONCLUSION</b>The changes of beta-adrenergic receptor mRNA expression are associated with the severity of heart failure.</p>

PTEN negatively regulates isoproterenol-induced cardiac hypertrophy and effects of captopril on PTEN expression / 中华心血管病杂志

<p><b>OBJECTIVE</b>To examine the negative regulation role of PTEN in isoproterenol-induced cardiac hypertrophy by testing the expression of PTEN mRNA and protein and to explore the effects of captopril (Cap) on PTEN expression.</p><p><b>METHODS</b>Twenty four rats were randomly divided into three groups: control group, ISO group, and ISO+Cap group. The following parameters were examined:body weight (BW), heart weight (HW), left ventricular weight (LVW), left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP) and +/- dp/dt(max). The ratio of HW/BW and LVW/BW was calculated. PTEN mRNA and protein were tested by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>(1) Compared with the control group, the ratio of HW/BW and LVW/BW, LVEDP and LVESP were all increased in ISO group and ISO+Cap group (P < 0.05), but +/- dp/dt(max) was decreased (P < 0.05); (2) compared with the ISO group, the ratio of HW/BW and LVW/BW, LVEDP, LVESP were all decreased in ISO+Cap group (P < 0.05), but +/- dp/dt(max) was increased (P < 0.05); (3) compared with the control group, PTEN mRNA and protein were up-regulated in ISO group and ISO+Cap group; (4) compared with the ISO group, PTEN mRNA and protein were up-regulated in ISO+Cap group.</p><p><b>CONCLUSIONS</b>PTEN mRNA and protein are up-regulated in isoproterenol-induced cardiac hypertrophy. Captopril can up-regulate PTEN expression in cardiac hypertrophy. There is a negative regulative mechanism in cardiac hypertrophy process, in which PTEN is probably an endogenous negative regulator of cardiac hypertrophy.</p>