The Size Differences of Breast Cancer and Benign Tumors Measured by Two-Dimensional Ultrasound and Contrast-Enhanced Ultrasound.

OBJECTIVES: Ultrasound (US) imaging has been observed to underestimate tumor size in clinical practice. This study aims to compare the size measurements of breast cancer and benign tumors using two-dimensional ultrasound (2DUS) and contrast-enhanced ultrasound (CEUS). METHODS: The study included 42 clinically confirmed breast cancer and 47 benign breast tumors. Two experienced physicians independently measured the maximal longitudinal and transverse diameters of the masses in 2DUS and CEUS. All analyses were performed in R (4.2.2) and GraphPad Prism 6. RESULTS: The maximal longitudinal and transverse diameters of breast cancer measured by CEUS were 26.61 ± 0.21% and 26.24 ± 0.19% larger compared with 2DUS, and benign breast tumors had an 11.74 ± 0.21% and 11.06 ± 0.14% increase in size compared with 2DUS. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the difference between 2DUS and CEUS was 0.870 for longitudinal diameters (95% CI: 0.795-0.945, sensitivity 0.842, specificity 0.783, threshold value 0.215), and 0.863 for transverse diameters (95% CI: 0.785-0.942, sensitivity 0.667, specificity 0.936, threshold value 0.203). CONCLUSIONS: The size measurements of both breast cancer and benign tumors were larger in CEUS compared with 2DUS, with CEUS measurements of breast cancer being more pronounced than those of benign breast tumors. These findings suggest that CEUS may provide a more precise assessment of tumor size, which is crucial for determining optimal treatment strategies and improving patient outcomes in breast cancer management.

Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial.

GST-HG131, a novel dihydroquinolizinone (DHQ) compound, has been shown to reduce circulating levels of HBsAg in animals. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetic profile of GST-HG131 in healthy Chinese subjects. This was a double-blind, randomized, placebo-controlled phase Ia clinical trial that was conducted in two parts. Part A was a single-ascending-dose (SAD; GST-HG131 10 30, 60, 100, 150, 200, 250 or 300 mg or placebo) study, which also assessed the food effect of GST-HG131 100 mg. Part B was a multiple-ascending-dose (MAD; GST-HG131 30, 60 or 100 mg or placebo BID) study. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. PK analyses were conducted in blood, urine, and fecal samples. Single doses of GST-HG131 ≤ 300 mg and multiple doses of GST-HG131 ≤ 60 mg were generally safe and well tolerated; however, multiple dosing was stopped at GST-HG131 100 mg, as pre-defined stopping rules specified in the protocol were met (Grade II drug related AEs of nausea and dizziness in >50% of subjects). In the SAD study, median tmax of GST-HG131 was 1-6 h, and t1/2 ranged from 3.88 h to 14.3 h. PK parameters were proportional to dose. Exposure was reduced after food intake. In the MAD study, steady-state was attained on day 4, and there was no apparent plasma accumulation of GST-HG131 on day 7 (Racc < 1.5). In conclusion, GST-HG131 exhibited an acceptable safety profile in healthy subjects at single doses ranging from 10-300 mg and multiple doses (BID) ranging from 30-60 mg, and the MAD doses (30 mg and 60 mg BID) that potentially meet the therapeutic AUC requirements. These findings imply GST-HG131 has potential as a therapeutic option for CHB infection. (This study has been registered at ClinicalTrials.gov under identifier NCT04499443.).

Discovery and preclinical evaluations of GST-HG131, a novel HBV antigen inhibitor for the treatment of chronic hepatitis B infection.

Chronic hepatitis B (CHB) remains a significant health challenge worldwide. The current treatments for CHB achieve less than 10% cure rates, majority of the patients are on therapy for life. Therefore, cure of CHB is a high unmet medical need. HBV surface antigen (HBsAg) loss and seroconversion are considered as the key for the cure. RG7834 is a novel, orally bioavailable small molecule reported to reduce HBV antigens. Based on RG7834 chemistry, we designed and discovered a series of dihydrobenzopyridooxazepine (DBP) series of HBV antigen inhibitors. Extensive SAR studies led us to GST-HG131 with excellent reduction of HBV antigens (both HBsAg and HBeAg) in vitro and in vivo. GST-HG131 improved safety in rat toxicology studies over RG7834. The promising inhibitory activity, together with animal safety enhancement, merited GST-HG131 progressed into clinical development in 2020 (NCT04499443).

Copper-Catalyzed Chemoselective and Enantioselective Friedel-Crafts 1,2-Addition of Pyrrole with ß,γ-Unsaturated α-Ketoesters.

A Friedel-Crafts alkylation of pyrrole was developed to afford the ß,γ-unsaturated α-hydroxy esters bearing a quaternary stereogenic center with good enantioselectivities and yields. This protocol represents the first report of 1,2-addition of Friedel-Crafts alkylation of pyrrole to ß,γ-unsaturated α-ketoesters.

Asymmetric Formal Aza-Diels-Alder Reaction of Trifluoromethyl Hemiaminals with Enones Catalyzed by Primary Amines.

A primary amine-catalyzed asymmetric formal aza-Diels-Alder reaction of trifluoromethyl hemiaminals with enones was developed via a chiral gem-diamine intermediate. This novel protocol allowed facile access to structurally diverse trifluoromethyl-substituted piperidine scaffolds with high stereoselectivity. The utility of this method was further demonstrated through a concise approach to biologically active 4-hydroxypiperidine. More importantly, a stepwise mechanism involving an asymmetric induction process was proposed to rationalize the positive correlation between the chirality of the gem-diamine intermediate and the formal aza-Diels-Alder product.

Copper-Catalyzed Enantioselective Hetero-Diels-Alder Reaction of Danishefsky's Diene with Glyoxals.

The highly enantioselective hetero-Diels-Alder reaction of Danishefsky's diene with glyoxals was developed by virtue of a readily accessible chiral copper catalyst. This efficient transformation provided a facile and scalable access to a wide range of biologically active dihydropyrones with a high level of enantioselectivities. Moreover, the substrate scope of this reaction could be extended to isatins with this catalytic system. More importantly, the mechanism involved in this reaction was proposed on the basis of the unambiguous structures of intermediates.

Highly Diastereo- and Enantioselective Michael Addition of Nitroalkanes to 2-Enoyl-Pyridine N-Oxides Catalyzed by Scandium(III)/Copper(II) Complexes.

A C2 -symmetric Schiff-base ligand, derived from tridentate-Schiff-base, was developed and successfully applied to the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. With this newly catalytic system, an unprecedented diastereoselectivity was obtained in the asymmetric Michael addition of nitroalkanes to 2-enoyl-pyridine N-oxides. In addition, a switch in enantioselectivity was achieved by using this newly catalytic system and our previous catalyst. After a facile reduction, the optically active adduct was converted to a biologically active dihydro-2H-pyrrol 4 a. Furthermore, a connection of two tridentate-Schiff-base subunits proved to be an effective strategy in ligand design.

Enantioselective copper(I/II)-catalyzed conjugate addition of nitro esters to ß,γ-unsaturated α-ketoesters.

A highly enantioselective Michael addition of nitroacetates to ß,γ-unsaturated α-ketoesters was developed by using chiral copper catalysts. The Michael addition products can be obtained in high yields with up to 99 % ee. With these densely functionalized products, the chiral cyclic nitrones, which are important synthetic intermediates, can be obtained in one step.

Baduanjin exercise intervention trial: research protocol of a randomised controlled trial for frail kidney transplant recipients.

INTRODUCTION: Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs. METHODS AND ANALYSIS: This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software. ETHICS AND DISSEMINATION: The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings. TRIAL REGISTRATION NUMBER: ChiCTR2100041730.

Baduanjin Mind-Body Exercise for Cancer-Related Fatigue: Protocol for a Remotely Delivered Randomized Wait-List Controlled Feasibility Study.

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.

[Effects of simvastatin on expression of connective tissue growth factor in vitreous and retina of diabetic rats].

OBJECTIVE: To study the effects of simvastatin on the expression of connective tissue growth factor (CTGF) that cause fibrosis in the vitreous and retina after intravitreal injection in diabetic rats, and to explore the safety of this procedure. METHODS: It was an experimental study. Forty adult male Wistar rats were randomly divided into normal control group (10 rats) and diabetes mellitus group (30 rats). Four months later, according to whether treated with simvastatin or not, the diabetes mellitus group randomly divided into simvastatin intervention group (20 rats) and diabetic positive control group (10 rats). Simvastatin was injected into the vitreous in the simvastatin intervention group, but not in the diabetic positive control group. Seven days later, after the examination of electroretinogram (ERG), all rats were sacrificed, and their eyeballs were enucleated. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry method were performed to determine the expression of CTGF in the vitreous and retina. Terminal DNA transferase-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptosis of retina cells. Concentration of CTGF in the vitreous, retinal expression of CTGF, retinal cellular apoptosis index, ERG-b wave and oscillatory potentials (OPs) of rats in each group were compared using analysis of variance LSD test methods. RESULTS: No systemic toxic reactions, no lens opacity and no endophthalmitis occurred after injection of simvastatin into the vitreous of rats. Concentrations of CTGF in vitreous of simvastatin intervention group, diabetes positive control group and normal control group rats were 359.21 µg/L, 478.47 µg/L and 210.78 µg/L, respectively (F = 252.366, P < 0.05). The levels of CTGF in the vitreous of simvastatin intervention group and diabetic positive control group was significantly higher than that of the normal control group and showed significant difference (t = 12.123, 23.816;P < 0.05). CTGF levels in simvastatin intervention group were significantly lower than those in diabetic positive control group, and the difference was statistically significant. (t = 11.693, P < 0.05). The results of immunohistochemical staining and TUNEL staining were negative in the normal control group. Retinal expression of CTGF in simvastatin intervention group and diabetic positive control group were (26.60 ± 2.95)% and (42.31 ± 2.59)%, respectively. Retinal expression of CTGF in simvastatin intervention group was reduced as compared to the diabetic positive control group, the difference was statistically significant (t = 12.112, P < 0.05). Retinal cellular apoptosis index of simvastatin intervention group and diabetic positive control group was 0.19 ± 0.02 and 0.25 ± 0.03, respectively. Retinal cellular apoptosis index of simvastatin intervention group was significantly lower than that in diabetic positive control group (t = 4.745, P < 0.05). ERG revealed no significant changes. In simvastatin intervention group as compared with diabetic positive control group. CONCLUSIONS: Simvastatin could inhibit the expression of CTGF in the vitreous body and retina in diabetic rats. Intravitreal injection of simvastatin is a relatively safe procedure.

Predictive value of the echocardiographic noninvasive myocardial work index for left ventricular reverse remodeling in patients with multivessel coronary artery disease after percutaneous coronary intervention.

Background: Coronary artery disease (CAD) can lead to left ventricular (LV) remodeling, which, in adverse cases, has been associated with heart failure and increased mortality. Here, we aimed to evaluate the predictive value of the noninvasive myocardial work index (NIMWI) for LV reverse remodeling in patients with multivessel CAD after percutaneous coronary intervention (PCI). Methods: A total of 88 consecutive patients with multivessel CAD treated with PCI were identified and categorized according to the presence of LV reverse remodeling 3 months after PCI [≥15% decrease in the LV end diastolic volume (LVEDV)]. With the LV pressure-strain loop (PSL) technique, NIMWIs, including the global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were statistically compared between the reverse LV remodeling group and nonreverse LV remodeling group 1 week before PCI. Results: Significantly lower GWI, GCW, and GWE, and significantly higher GWW were observed in the reverse LV remodeling group compared with the nonreverse LV remodeling group (P<0.05). Left ventricular mass index (LVMI), GCW, and GWE were independently associated with early LV reverse remodeling. Receiver operating characteristic (ROC) curve analysis demonstrated that GCW was the most powerful predictor of early LV reverse remodeling in patients with CAD [area under the curve (AUC) =0.867]. The optimal cutoff GCW value predictive of early LV reverse remodeling was 1,438.5 mmHg% (sensitivity, 85%; specificity, 70%). Conclusions: GCW, among the NIMWIs, may be the major predictor of LV reverse remodeling in patients with multivessel CAD after PCI. NIMWI could potentially provide a new reference index for the quantitative evaluation of LV myocardial work.

Application value of myocardial work technology by non-invasive echocardiography in evaluating left ventricular function in patients with chronic heart failure.

BACKGROUND: Accurate evaluation of left ventricular (LV) systolic function is the premise for diagnosing and treating chronic heart failure. This study aimed to explore the incremental value of echocardiographic myocardial work in evaluating the LV systolic dysfunction in patients with chronic heart failure. METHODS: A total of 206 participants were enrolled, including 155 patients with chronic heart failure and 51 healthy controls (HC). The chronic heart failure patients were divided into three groups according to LV ejection fraction (LVEF): Heart failure with preserved ejection fraction (HFpEF group, 54 cases, LVEF ≥50%), heart failure with mid-range ejection fraction (HFmrEF group, 50 cases, 40%≤ LVEF <50%), and heart failure with reduced ejection fraction (HFrEF group, 51 cases, LVEF <40%). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters, including the global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were calculated in the study participants. One-way analysis of variance test followed by Fisher's least significant difference (LSD) t-test were used to obtain parameters with significant differences, which were then fed into a machine learning model established for subsequent multi-classification of the four groups. The selected myocardial work parameters with high importance rankings resulting from the machine learning model were further compared with the traditional LVEF in the multi-classification of the four groups. RESULTS: All conventional echocardiographic parameters were significantly different between the HFmrEF and HFrEF groups, but only E/e', left atrium showed notable differences between the HFpEF and HC groups (P<0.05). All myocardial work parameters were markedly different between the four groups (P<0.05). LVEF and GWI were more important than the other parameters according to the multi-classification machine learning model. The multi-classification diagnostic performances of LVEF, GWI, and LVEF + GWI were 82%, 88%, and 98%, respectively, which confirmed that GWI + LVEF could complementarily improve the diagnosis accuracy in classifying the four groups, with a performance increase of approximately 10% than each individually. CONCLUSIONS: GWI can play a complementary role to LVEF in the early diagnosis of HFpEF patients from the HC group and improve the clinical evaluation accuracy in chronic heart failure patients. Echocardiographic myocardial work should be utilized along with conventional LVEF to evaluate the systolic function of chronic heart failure patients in clinical practice.

Evaluation of myocardial work in patients with hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy based on non-invasive pressure-strain loops.

Background: The capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI). Methods: Conventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH. Results: Compared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%. Conclusion: NMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.

[Recent advances in the studies of the inhibition of fibrosis in proliferative diabetic retinopathy].

Proliferative fibrotic membranes in Proliferative diabetic retinopathy (PDR) cause severe harm to the patients' visual function. It is critical to inhibit the occurrence and development of fibrosis in order to preserve the visual function of the patients in advanced stage of diabetic retinopathy. In recent years, reports about inhibiting neovascularization in PDR are common. It is rare to find reports about inhibiting fibrosis formation. The application of angiotensin converting enzyme inhibitor, vascular endothelial growth factor receptor antagonist, HMG coenzyme A reductase inhibitors and steroids could inhibit the formation of fibrosis at varying degrees by targeting different pathways. Therefore, it is necessary to summarize the basis of current research conditions for the inhibition of the formation of proliferative fibrotic membranes in PDR, which will provide extensive ideas for the treatment of PDR and fibrosis formation.

[Role of endothelial progenitor cells in optic nerve injury of rats].

OBJECTIVE: To investigate the role of endothelial progenitor cells (EPC) in the injury of rat optic nerve. METHODS: An experimental study. The rat model of optic nerve injury was created by fluid percussion brain injury device (FPI). On hundred and eight rats (108 eyes) were divided into 2 groups randomly. Each group was further divided into 9 subgroups by the time of injury (24 h before and 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury). The number of circulating EPCs was measured, HE staining of the optic nerve, immunohistochemistry study of CD31 (markers of vascular endothelial cells) and flash-visual evoked potential (F-VEP) were observed at every time point. Two independent sample t-test was used for the comparison between the control group and the optic nerve injury groups at the same time point. The correlation between different items was analyzed by Pearson test. P value less than 0.05 was considered significant. RESULTS: The number of EPCs in normal rats was 46-52/200 000 monocytes. After traumatic optic nerve injury, the number of EPCs was (34 ± 4, 34 ± 5, 69 ± 9, 76 ± 6, 107 ± 9, 69 ± 7, 58 ± 6 and 56 ± 4)/200 000 monocytes at 3, 12, 24, 48, 72 h, and 1, 2 and 3 weeks. The difference of number of EPCs between the experiment and control groups was significant at 3, 12, 24, 48, 72 h and 1 and 2 weeks after the injury (t = 5.29, 2.90, -4.30, -7.61, -14.17, -5.74 and -2.79; P < 0.05). The number of CD31(+) cell in the optic nerve and surround tissues in normal rats was (7-9)/5 high magnification field. After the injury, the number of CD31(+) cell was 8.36 ± 1.52, 7.17 ± 1.10, 10.41 ± 1.92, 11.43 ± 1.58, 14.29 ± 2.03, 17.33 ± 1.47, 17.86 ± 1.22 and 18.13 ± 1.40 at different time points. The difference of number of CD31(+) cell between the experiment and control groups was significant at 48, 72 h, and 1, 2, and 3 weeks after the injury (t = 4.31, -7.61, -8.17, -10.08, and -10.79; P < 0.05). The number of microvessels in the optic nerve and surround tissues in normal rats was 6-9/5 high magnification field. After traumatic optic nerve injury, the number of microvessels was 7.54 ± 2.01, 8.52 ± 2.21, 11.02 ± 1.62, 15.40 ± 2.04, 18.39 ± 1.96, 23.21 ± 1.50, 22.78 ± 2.40 and 24.13 ± 2.51 at different time points. The difference of number of microvessels between the experiment and control groups was significant at 48, 72 h, 1, 2, and 3 weeks after the injury (t = 4.25, -7.74, -8.26, -10.28 and -11.49; P < 0.05). The latency period of P waves was decreased at 3 h and increased to above basic level at 24 h, and then tend to be stable. The difference of latency period of P waves between the experiment and control groups was significant at 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 4.15, 3.74, 5.84, 6.08, 6.40, 6.52, 6.53 and 6.61; P < 0.05). The amplitude of F-VEP was decreased at 3 h and increased to the basic level at 12 h, then decreased to below the basic level gradually. The difference of the amplitude of F-VEP between the experiment and control groups was significant at 3, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 3.95, 4.14, 5.26, 5.78, 6.49, 6.72 and 6.23; P < 0.05). The number of EPCs was correlated with the number of CD31(+) cell, microvessels and F-VEP (r = 0.43, 0.41 and 0.43; P < 0.01). CONCLUSIONS: The present study showed that the number of EPCs in the blood increases significantly after traumatic optic nerve injury, and the cells can arrive the traumatic area to repair injured tissue and enhance angiogenesis.

[Retinal cell apoptosis, microvascular changes and expression of connective tissue growth factor in experimental diabetic rats].

OBJECTIVE: To study the cell apoptosis and the expression of connective tissue growth factor (CTGF) in the retina of diabetic rats and to explore their contributions to the changes of microcirculation. METHODS: It was a experiment study. Fifty-five adult male Wistar rats were divided into two groups, normal control group (CON, 10 rats) and diabetes mellitus group (DM, 45 rats). The 30 surviving rats in the DM group were further divided into 3 groups based on the time of observation, 2 month (DM2), 4 month (DM4) and 6 month (DM6) groups, with 10 rats in each group. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). Expression of CTGF was determined by immunohistochemical study. Retinal vessels were observed by retinal digest stretched periodic acid Schiff (PAS) staining. RESULTS: Immunohistochemical staining and TUNEL staining revealed negative results in normal control group. Retinal cell apoptosis index increased gradually from DM2 to DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 21.432, 50.843, 29.410; P < 0.05). Expression of CTGF in the retina increased from DM2-DM6, the differences between any two groups were statistically significant (t(2-4, 2-6, 4-6) = 15.345, 26.316, 10.971; P < 0.05). PAS staining of retinal blood vessels obtained negative results in the CON and DM2 groups. Part of retinal capillaries were slightly stiff and narrow in DM4 group. Retinal capillaries in DM6 group were trunk stiff and were narrowed obviously. The number of pericytes was reduced in DM4, and progressed following the course of diabetes. The number of pericytes in the DM2 group did not different from that in the CON group (t = 0.875, P = 0.387). The number of pericytes in the DM4 and DM6 group were significantly decreased as compared to the CON group (t = 3.367, 6.667; P < 0.05). Retinal cellular apoptosis index had a significant positive correlation to the expression of CTGF (r = 0.958, P < 0.05). Number of pericytes was significantly correlated (negative correlation) with retinal cellular apoptosis index and the expression of CTGF (r = -0.540, -0.595; P < 0.05). CONCLUSIONS: The appearances of cellular apoptosis and fibrosing factor CTGF in the retina of diabetic rats occurred earlier than the changes of microcirculation and the number of capillary pericytes.

Quantitative Analysis of Myocardial Work by Non-invasive Left Ventricular Pressure-Strain Loop in Patients With Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a common risk factor for cardiovascular diseases. The aims of this study were to evaluate the changes in the left ventricular myocardial work in T2DM patients using the left ventricular pressure-strain loop (PSL) technique, and to explore the risk factors for the left ventricular myocardial work impairment. Methods: Fifty patients with T2DM and 50 normal controls (NCs) were included in the study. In addition to conventional echocardiography and two-dimensional speckle tracking echocardiography, the left ventricular myocardial work parameters were measured using PSL technology. Results: The absolute value for global longitudinal strain (GLS), global work index (GWI) and, global constructive work (GCW) were significantly decreased in the T2DM group (P < 0.05), while the left ventricular ejection fraction (LVEF) was not significantly different between the T2DM and NC groups. Multivariable linear regression analysis showed that hemoglobin A1c (HbA1c) was independently related to GWI (ß = -0.452, P < 0.05), while HbA1c and the diabetes duration were independently related to GCW (ß = -0.393, P < 0.05 and ß = -0.298, P < 0.05, respectively). Conclusions: Changes in the left ventricular myocardial systolic function in T2DM patients were identified using PSL technology. HbA1c was shown to be an independent risk factor affecting GWI, while HbA1c and diabetes duration were demonstrated to be independent risk factors affecting GCW.

Association Between Echocardiographic Non-invasive Myocardial Work Indices and Myocardial Fibrosis in Patients With Dilated Cardiomyopathy.

Objectives: To analyze the association between global myocardial work indices evaluated by non-invasive left ventricular (LV) pressure-strain loop (PSL) and LV myocardial fibrosis in patients with dilated cardiomyopathy (DCM). Methods: A total of 57 patients with DCM were included in this prospective study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS) were measured using LVPSL. LV volumes and LV ejection fraction (LVEF) were evaluated using cardiac magnetic resonance imaging (CMRI), LV myocardial fibrosis was estimated at CMRI by qualitative assessment of late gadolinium enhancement (LGE). According to the CMRI, the studied population was divided into two groups, namely: patients without LGE (LGE-) and patients with LGE (LGE+). Results: The LGE+ group presented with increased age, LV end systolic volume (LVESV) index and reduced GWI, GCW, GWE, GLS, CMRI-derived LVEF (LVEFCMRI), the differences between the two groups were statistically significant (P < 0.05). After correcting for age and LVESV index, LVEFCMRI, GLS, GWI, GCW, and GWE retained independent associations with LV myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, LVEFCMRI, and GCW showed larger AUC and higher accuracy, sensitivity, and specificity than GLS, the accuracy of predicting LV myocardial fibrosis ranged from high to low as: LVEFCMRI, GCW, GWE, GWI, and GLS. Conclusions: LVEFCMRI, GWI, GCW, GWE, and GLS remained significant predictors of LV myocardial fibrosis. LVEFCMRI, and GCW appeared to better predict LV myocardial fibrosis compared with GLS.