Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

[Roles of long non-coding RNAs in prostate cancer and their action mechanisms].

Prostate cancer (PCa) is one of the most common male malignancies as well as one of the frequent causes of tumor-induced death. Long non-coding RNAs (lncRNAs) are RNA transcripts that are more than 200 nucleotides in length, lack an open reading frame, and do not encode proteins. LncRNAs are abnormally expressed in most tumors including PCa and closely related to the recurrence, metastasis and prognosis of PCa. LncRNAs regulate gene expressions at multiple levels such as epigenetics, transcription and post-transcription, change metabolic pathways, and play a carcinogenic or anti-tumor role in the development and progression of PCa. Continuous androgen receptor (AR) signal transduction is one of the key features of castration-resistant PCa. This review briefly introduces the role of lncRNAs as oncogenes or tumor suppressor genes in the development and progression of PCa, and expounds the possible molecular mechanisms of lncRNAs mediating PCa through the AR signaling pathway, post-transcriptional regulation represented by ceRNA, and tumor metabolism, aiming to provide potential biomarkers and therapeutic targets for the clinical diagnosis and treatment of PCa.

The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study : Prevalence of H type hypertension.

BACKGROUND: H type hypertension is defined as homocysteine (Hcy) ≥ 10 µmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives. METHODS: We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected. RESULTS: In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 µmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension. CONCLUSIONS: The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.

[Long noncoding RNA Linc00662 promotes the tumorigenesis of prostate cancer cells].

OBJECTIVE: To investigate the expression of Linc00662 in PCa and its influence on the biological function of PCa cells. METHODS: Using qRT-PCR, we detected the expression of Linc00662 in the PCa tissue and cell lines and that in the adjacent normal prostatic tissue and epithelial WPMY-1 cells and analyzed the correlation between the expression of Linc00662 and the clinicopathological features of the PCa tissue. We transfected PC-3 and DU145 cells with siRNA, and verified the interference efficiency by qRT-PCR. We examined the effects of interfering with the Linc00662 expression on the proliferation, apoptosis, migration and invasiveness of PC-3 and DU145 cells by CCK-8 assay, Caspase 3/9 activity assay, wound-healing assay and Transwell invasion assay. RESULTS: The expression of Linc00662 in the PCa tissue and cell lines was significantly up-regulated compared with that in the adjacent normal prostatic tissue and epithelial cells (P < 0.01), and the high expression of Linc00662 was positively correlated with the tumor stage (P = 0.002), primary tumor size (P = 0.006), lymph node metastasis (P = 0.001) and distant metastasis (P = 0.001). Transfection of si-Linc00662 into the PC-3 and DU145 cells significantly reduced the expression of Linc00662 (P < 0.01). Compared with the normal control, the PC-3 and DU145 cells in the Linc00662 interference group showed remarkably decreased proliferation, invasion and migration abilities (P < 0.01), but an increased rate of apoptosis (P < 0.01). CONCLUSIONS: Linc00662 is highly expressed in PCa tissues and cells relatively. Knockdown of the Linc00662 expression may inhibit the proliferation, migration and invasiveness and promote the apoptosis of PCa cells. Therefore, Linc00662 could be considered as a new marker of PCa.

Correlation between cancer-related cognitive impairment and resting cerebral glucose metabolism in patients with ovarian cancer.

Background: An increasing number of research have applied neuroimaging techniques to explore the potential neurobiological mechanism of Cancer-related cognitive impairment (CRCI). Purpose: To explore the correlation between resting brain glucose metabolism and CRCI using 18F-FDG PET/CT in ovarian cancer (OC) patients. Methods: From December 2021 to March 2022, 38 patients with OC were selected as the study group, and 38 healthy women of the same age (±1 year) who underwent routine physical examination using PET/CT were selected as the control group. Patients received further assessment with the Montreal Cognitive Assessment Scale (MoCA) and Perceived Deficit Questionnaire (PDQ). Independent sample t-test and Spearman correlation were conducted for data analysis. Results: The resting brain glucose metabolism in the OC group was significantly lower than in the healthy controls. 60.52 % patients had neuropsychological impairment and retrospective memory were the most serious perceived cognitive impairments. The resting brain glucose metabolism in OC patients did not significantly correlate with neuropsychological performance but had significant positive correlation with subjective cognitive evaluation. Discussion: Resting glucose metabolism was low in OC patients and associated with subjective cognitive impairment but not objective neuropsychological test results. 18F-FDG PET/CT can be used to evaluate brain function in OC patients and provide reliable imaging indicators for early recognition of and intervention for changes in cognitive function.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

The therapeutic potential of G-CSF in pressure overload induced ventricular reconstruction and heart failure in mice.

In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction that is normalized by microtubule depolymerization. In this study, 86 male mice were divided into seven groups. The transverse ascending aorta constriction (TAC) in six groups were performed in order to make heart failure model. Mice in each group were injected with G-CSF or/and telmisartan subcutaneously at different time respectively. Results showed that reduction in left ventricular volume and improved function persisted at 2 week, but recurrent dilatation at 4 weeks was associated with a loss of functional improvement. Compared with PBS group, the expression of VEGF protein and HIF-1 mRNA were significantly higher in mice injected with G-CSF or/and telmisartan (P<0.05). The expression of p53 mRNA, myocardial fibrosis and mortality were significantly lower in mice injected with G-CSF or/and telmisartan (P<0.05). It could be concluded that G-CSF can delay the progression of pressure overload induced ventricular reconstruction and heart failure in mice.

A novel risk assessment model of contrast-induced nephropathy after percutaneous coronary intervention in patients with diabetes.

The purpose of our study was to develop a simple clinical pre-procedure risk model based on clinical characteristics for the prediction of contrast-induced nephropathy (CIN) and major adverse cardiac events (MACEs) after percutaneous coronary intervention (PCI) in patients with diabetes. A total of 1113 patients with diabetes who underwent PCI with contrast exposure were randomized into a development group (n = 742) and a validation group (n = 371) in a 2:1 ratio. CIN was defined as an increase of either 25% or 0.5 mg/dL (44.2 µmol/L) in serum creatinine within 72 hours after contrast infusion. A simple CIN risk score based on independent predictors was established. Four variables were identified for our risk score model: LVEF < 40%, acute coronary syndrome (ACS), eGFR < 60, and contrast volume > 300 mL. Based on this new CIN risk score, the incidence of CIN had a significant trend with increased predicting score values of 5.9%, 32.9% and 60.0%, corresponding to low-, moderate- and high-risk groups, respectively. The novel risk assessment exhibited moderate discrimination ability for predicting CIN, with an AUC of 0.759 [95% CI 0.668-0.852, P = .001] in the validation cohort. It also had similar prognostic values for one-year follow-up MACE (C-statistic: 0.705 and 0.606 for new risk score and Mehran score, respectively). This novel risk prediction model could be effective for preventing nephropathy in diabetic patients receiving contrast media during surgical procedures.

Safety of dose escalation by simultaneous integrated boosting radiation dose within the primary tumor guided by (18)FDG-PET/CT for esophageal cancer.

PURPOSE: To observe the safety of selective dose boost to the pre-treatment high (18)F-deoxyglucose (FDG) uptake areas of the esophageal GTV. METHODS: Patients with esophageal squamous cell carcinoma were treated with escalating radiation dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment 50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade 3 or higher acute toxicities causing continuous interruption of radiation for over 1 week. RESULTS: From April 2012 to February 2014, dose has been escalated up to LEVEL 4 (70Gy). All of the 25 patients finished the prescribed dose without DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2 died of esophageal hemorrhage within 1 month after completion of radiotherapy, which was not definitely correlated with treatment yet. Late toxicities remained under observation. With median follow up of 8.9months, one-year overall survival and local control was 69.2% and 77.4%, respectively. CONCLUSIONS: Dose escalation in esophageal cancer based on (18)FDG-PET/CT has been safely achieved up to 70Gy using the SIB technique. Acute toxicities were well tolerated, whereas late toxicities and long-term outcomes deserved further observation.

Short-term safety and efficiency of cryoablation for renal sympathetic denervation in a swine model.

BACKGROUND: Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control. Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%-20% of treated patients are nonresponders to radiofrequency denervation. The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN. METHODS: Seven swines randomly assigned to two groups: Renal cryoablation (CR) group and control group. The control group underwent renal angiogram only. The CR group underwent renal angiogram plus bilateral renal cryoablation. Renal angiograms via femoral were performed before denervation, after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis. Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves. RESULTS: Cryoablation did not induce severe complications at any time point. There was no significant change in diameter of renal artery. CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg. There was a slight but insignificant decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation. Compared with the control group, renal tissue NE of CR group decreased by 89.85%. CONCLUSIONS: Percutaneous catheter-based cryoablation of the renal artery is safe. CR could effectively reduce NE storing in the renal cortex, and the efficiency could be maintained 28-day at least.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

BACKGROUND: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. MATERIALS AND METHODS: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. RESULTS: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. CONCLUSIONS: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Variation in background intensity affects PET-based gross tumor volume delineation in non-small-cell lung cancer: the need for individualized information.

PURPOSE: Efficient tumor volume delineation by the combined use of PET/CT scanning is necessary for the proper treatment of non-small cell lung cancer (NSCLC). To understand the effect of variation in background intensity on PET-based gross tumor volume (GTV) delineation, we determined the background standard uptake values (SUVs) in normal lung, aorta (blood pool), and liver tissues and determined GTVs using different methods. METHODS: Thirty-seven previously untreated patients with pathologically confirmed NSCLC underwent PET/CT scanning with (18)F-fluorodeoxyglucose ((18)F-FDG). To obtain (18)F-FDG uptake values in normal tissues, regions of interest in the lung lobes (left upper, left lower, right upper, right middle, and right lower), aorta, and liver zones (left, intermediate, and right) were measured. The coefficient of variation (CV) of the SUV was measured for each normal structure. The CT-based GTV (GTV(CT)) was considered as the standard to which all PET-based GTVs were compared, and the correlation coefficient was analyzed to compare GTV obtained by the various delineation methods. Linear and logarithmic regression analyses were used to determine the relationship between GTV(CT) and GTV(PET). RESULTS: Normal lung tissue showed a significantly lower SUV and less stability than tissue of the aorta or liver. For the lung, aorta, and liver, the maximum SUV (SUV(max)) was 0.82 ± 0.32, 2.35 ± 0.37, and 3.24 ± 0.50 (CV: 38.79%, 15.82%, and 15.30%) and average SUV (SUV(ave)) was 0.49 ± 0.18, 1.68 ± 0.32, and 2.34 ± 0.36 (CV: 36.38%, 18.92%, and 15.44%), respectively. The SUVs of the lung varied from lobe to lobe. The GTV delineation method using the SUV(ave) of the lung lobe in which the tumor was found as background in the source-to-background ratio (SBR) method showed the best correlation with the volume of CT-based GTV (r=0.81). CONCLUSIONS: Our results show vast variation in the SUV among normal tissues, as well as in the different lung lobes. The tumor volume delineated using the SBR method correlated well with the CT-based tumor volume. We conclude that it is reasonable and precise to contour GTV in patients with NSCLC after taking into account the background intensity of the lung lobe in which the tumor is found.

[Impacts of ultraviolet irradiation on the sperm motility and longevity of Acipenser baerii].

This paper studied the impacts of different dose ultraviolet irradiation (254 nm, UVC) on the sperm motility and longevity of Acipenser baerii. Ultraviolet irradiation had significant impacts on the sperm motility, its fast motion time, and longevity. With the increasing dose of ultraviolet irradiation, the sperm motility decreased rapidly first, increased rapidly then, and decreased rapidly again. The sperm fast motion time had the similar variation trend as the sperm motility, but the sperm longevity kept decreasing with increasing dose of ultraviolet irradiation. When the ultraviolet irradiation dose increased to 288 mJ x cm(-2), the sperm fast motion disappeared; when the ultraviolet irradiation dose increased up to 324 mJ x cm(-2), the sperm had no motility and died. According to the "Hertwig effect", the optimum ultraviolet irradiation dose for inactivating A. baerii sperm was 216 mJ x cm(-2).

[Effects of storage medium and temperature on short-term storage of Acipenser baerii eggs].

This paper studied the effects of different storage medium (coelomic fluid, Hepes solution, and modified Ringer's solution), temperature (4 degrees C and 16 degrees C), and duration (4 h, 8 h, 16 h, and 24 h) on the short-term storage of Siberian sturgeon (Acipenser baerii) eggs. The results showed that storage medium, temperature, and duration all had significant effects on the fertilization rate, hatching success, and malformation of newly hatched larvae (P < 0.05). With the increase of storage duration, the fertilization and hatching rates decreased, while the malformation rate of hatched larvae increased. The A. baerii eggs stored at 16 degrees C had higher fertilization, hatching, and malformation rates but shorter holding time than those stored at 4 degrees C. The optimal conditions for the short-term storage of A. baerii eggs were Hepes solution prepared according to the biochemical composition of A. baerii coelomic fluid, 16 degrees C, and 4 h, under which, 86.36% fertilization rate, 94.74% hatching rate, and zero malformation would be obtained.