Mechanistic Target of Rapamycin Regulates the Oligodendrocyte Cytoskeleton during Myelination.

During differentiation, oligodendrocyte precursor cells (OPCs) extend a network of processes that make contact with axons and initiate myelination. Recent studies revealed that actin polymerization is required for initiation of myelination whereas actin depolymerization promotes myelin wrapping. Here, we used primary OPCs in culture isolated from neonatal rat cortices of both sexes and young male and female mice with oligodendrocyte-specific deletion of mechanistic target of rapamycin (mTOR) to demonstrate that mTOR regulates expression of specific cytoskeletal targets and actin reorganization in oligodendrocytes during developmental myelination. Loss or inhibition of mTOR reduced expression of profilin2 and ARPC3, actin polymerizing factors, and elevated levels of active cofilin, which mediates actin depolymerization. The deficits in actin polymerization were revealed in reduced phalloidin and deficits in oligodendrocyte cellular branching complexity at the peak of morphologic differentiation and a delay in initiation of myelination. We further show a critical role for mTOR in expression and localization of myelin basic protein (Mbp) mRNA and MBP protein to the cellular processes where it is necessary at the myelin membrane for axon wrapping. Mbp mRNA transport deficits were confirmed by single molecule RNA FISH. Moreover, expression of the kinesin family member 1B, an Mbp mRNA transport protein, was reduced in CC1+ cells in the mTOR cKO and in mTOR inhibited oligodendrocytes undergoing differentiation in vitro These data support the conclusion that mTOR regulates both initiation of myelination and axon wrapping by targeting cytoskeletal reorganization and MBP localization to oligodendrocyte processes.SIGNIFICANCE STATEMENT Myelination is essential for normal CNS development and adult axon preservation and function. The mechanistic target of rapamycin (mTOR) signaling pathway has been implicated in promoting CNS myelination; however, there is a gap in our understanding of the mechanisms by which mTOR promotes developmental myelination through regulating specific downstream targets. Here, we present evidence that mTOR promotes the initiation of myelination through regulating specific cytoskeletal targets and cellular process expansion by oligodendrocyte precursor cells as well as expression and cellular localization of myelin basic protein.

Isolated ventricular apical hypoplasia: A report of four cases and literature review.

Isolated ventricular apical hypoplasia (IVAH) is a rare congenital cardiac anomaly, with clinical manifestations depending on the age of the patient, ranging from no symptoms in children to congestive heart failure or even malignant tachycardia in adults. Herein, we describe the clinical and anatomical findings in four cases with hypoplasia of the right or left ventricular apex, and we discuss the possible mechanisms and differential diagnosis of this malformation. Echocardiography is a rapidly accessible, low cost, noninvasive technique for the detection and evaluation of IVAH.

Clinical and radiological changes of hospitalised patients with COVID-19 pneumonia from disease onset to acute exacerbation: a multicentre paired cohort study.

OBJECTIVES: To analyse clinical and radiological changes from disease onset to exacerbation in coronavirus infectious disease-19 (COVID-19) patients. METHODS: We reviewed clinical histories of 276 patients with confirmed COVID-19 pneumonia and extracted data on patients who met the diagnostic criteria for COVID-19 severe/fatal pneumonia and had an acute exacerbation starting with mild or common pneumonia. RESULTS: Twenty-four patients were included. Of these, 8% were smokers, 54% had been to Wuhan, and 46% had comorbidities. Before acute exacerbation, elevated lactate dehydrogenase (232.9 ± 88.7) was present, and chest CT scans showed the number of involved lobes was 4 (2-5) and total CT score was 6 (2-8). Following acute exacerbation, patients were likely to have more clinical symptoms (p < 0.01) and abnormal laboratory changes (p < 0.01). The number of involved lobes and CT score after an exacerbation significantly increased to 5 (5-5) and 12 (9-14), respectively. Receiver operating characteristic (ROC) curve showed that, when the cutoff value of CT score was 5, the sensitivity and specificity for severe pneumonia were 90% and 70%, respectively. CT findings of ground glass opacity with consolidations (91.7%), bilateral distribution (100.0%), and multifocal lesion (100.0%) were features in found in patients after exacerbation. CONCLUSIONS: There are significant changes in clinical, laboratory, and CT findings in patients from disease onset to exacerbation. An increase in the number of involved lobes or an increased CT score from the baseline may predict poor clinical outcomes. Combining an assessment of CT changes with clinical and laboratory changes could help clinical teams evaluate the prognosis. KEY POINTS: • The common chest CT signs of COVID-19 pneumonia after exacerbation were ground glass opacity (GGO) with consolidation, bilateral distribution, and multifocal lesions. • An increase in number of involved lobes or an increased CT score from the baseline may predict a poor clinical outcome. • Worsened symptoms and abnormal laboratory results are also associated with poor prognosis.

[Systemic review of Jintiange Capsules in treatment of postmenopausal osteoporosis].

To systemically evaluate the efficacy and safety of Jintiange Capsules in the treatment of postmenopausal osteoporosis(PMOP).Seven literature databases were retrieved systematically,and two reviewers independently searched and screened studies,extracted data,and included all the randomized controlled trials on Jintiange Capsules in the treatment of PMOP.Interventions included comparison of Jintiange Capsules with placebo and routine treatment,and the studies on Jintiange Capsules combined with routine treatment versus conventional treatment were also included.The evaluation indicators of the study included at least one of the followings:fracture,quality of life,daily living ability,clinical symptoms,death,adverse events/adverse reactions,bone density,and bone metabolism indexes.The original study quality evaluation was conducted by following the Cochrane Handbook standard and statistical analysis was performed by using Rev Man 5.2.A total of 7 randomized controlled trials were included and the study quality was low.Meta-analysis showed that as compared with conventional treatment alone,Jintiange Capsules combined with conventional treatment showed more obvious effects in pain relief(MD=-0.98,95% CI[-1.55,-0.41],P=0.000 8),increasing blood calcium levels(MD=0.05,95% CI[0.02,0.09],P=0.003) and lowering serum alkaline phosphatase levels(MD=-12.92,95% CI[-24.09,-1.75],P=0.02).In addition,the Chinese patent medicine alone or in combination with conventional treatment was relatively safe.In conclusion,Jintiange Capsules has a certain effect in treating PMOP,but the quality of evidence is low.It is necessary to conduct well designed randomized controlled trials and select recognized evaluation indicators,especially the end outcomes in order to further improve the clinical evidence.

Hormetic Effects of Yttrium on Male Sprague-Dawley Rats.

To evaluate hormesis induced by Yttrium (Y) nitrate in male rats, Y was offered to F0 mother rats and F1 offspring at concentrations of 0, 20, 80, and 320 ppm daily from gestational day (GD) 0 through postnatal day 70 (PND 70). The F1 offspring were evaluated with respect to motor function, learning and memory, and histopathology. Administration of Y improved motor function in a dose dependent manner. In the 20 ppm group, body weight and spatial learning and memory were increased, while the latter was decreased in the 320 ppm group. Additionally, in the 20 ppm and 80 ppm, but not the 320 ppm groups, Y reduced the anogenital distance, which indicated an anti-androgen effect. These results suggest that Y follows a hormetic concentration-related trend with an inverted U-shape.

Isolated right ventricular apical hypoplasia characterized by computed tomography and echocardiography.

Isolated right ventricular apical hypoplasia is an unusual congenital heart disease that has been mentioned in only one report to our knowledge. We describe the case of a 62-year-old male patient suffering from recurrent abdominal distention, nausea, and lower extremity edema. The right ventricular morphologic abnormalities as shown by echocardiography and CT were comparable to those of left ventricular apical hypoplasia, suggesting right ventricular apical hypoplasia. However, this speculative diagnosis remains to be confirmed by additional cases. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:82-84, 2018.

Pneumopericardium as a rare complication after esophagopericardial fistula.

Pneumopericardium is a rare clinical entity which is often complicated by trauma. Pneumoperdicardium resulting after esophagopericardial fistula is much rarer. We present a case of pneumopericardium as the complication of esophagopericardial fistula in a 53-year-old man. After undergoing radiotherapy for 26 times, the patient got a fever and an unspecified thoracic pain. Echocardiography showed the rectilinear echoes in the pericardium. Chest computed tomography revealed pneumopericardium, pericardial effusion, recurrence of lung cancer, and pneumonia in right lower and left lung.

[Molecular cloning and tissue expression of the CCNG1 gene in sheep].

The CCNG1 gene encodes cyclin G1, which is an important cell cycle regulator and has been reported to be involved in reproductive biological processes, such as oocyte maturation and granule cell proliferation in mammals. But the study of CCNG1 in sheep has been rarely reported. To examine the effects of CCNG1 on estrous control and seasonal breeding in sheep, we first cloned and characterized the expression level of the sheep CCNG1 gene. Then by Real-time PCR, we detected and analyzed the expressions of CCNG1 gene at mRNA levels in the hypothalamus-pituitary-ovary (HPO) axis in different stages of an estrous cycle in Duo Lang sheep (non-seasonal breeding) and Merino sheep (seasonal breeding). The results showed that the open reading frame of the sheep CCNG1 gene is 885 bp in length and encodes 294 amino acids. Bioinformatic analysis indicated that the secondary structure of the sheep CCNG1 protein contained multiple phosphorylation sites and some Protein Kinase C phosphorylation sites. CCNG1 mRNA was identified in all tissues tested, with the levels in ovary and kidney higher than others. The expression profiles of CCNG1 in the HPO axis in different stages of an estrous cycle were similar in different sheep breeds: the expression levels of CCNG1 in the ovary, uterus, pineal gland and pituitary gland all peaked in the estrus phase. But there were significant differences for expression change extent of CCNG1 in ovaries in the oestrus and metestrus phase between different sheep breeds. The results suggested that CCNG1 probably participated in the regulation of estrous behavior and seasonal reproduction through controling the growth and development of follicles in sheep.

[Analysis of FABP4 expression pattern in rump fat deposition and metabolism of Altay sheep].

FABP4 (Fatty acid binding protein 4) is a hot candidate gene in fat deposition and lipid metabolism and participates in the transport and metabolism of intracellular free fatty acids. We aim to study the role of FABP4 in fat deposition and metabolism of the rump fat in Altay sheep. In this study, bioinformatics method was used to analyze the protein sequence homology among 10 species, and RT-PCR was employed to detect FABP4 tissue profiling of Altay sheep. An animal model simulating the rump fat deposition and metabolism of Altay sheep was established by continuous starvation, and qPCR and iTRAQ (isobaric tags for relative and absolute quantitation) were used to detecte FABP4 mRNA and protein expression changes in the control and continuous starvation groups, respectively. Sequence analysis showed that FABP4 protein sequence is highly conserved among species, suggesting an important biological function during evolution for FABP4. The RT-PCR result confirmed that FABP4 mRNA was highly expressed in intestinal and rump fat, suggesting that FABP4 plays an important physiological role in fat tissues. We did not find significant differences in FABP4 mRNA and protein between control and continuous starvation groups (P>0.05), which indicates that FABP4 may not be the key gene in fat deposition and metabolism in Altay sheep.The results above lay a foundation for further studies of FABP4 in rump or tail fat.

Bile acid flux through portal but not peripheral veins inhibits CYP7A1 expression without involvement of ileal FGF19 in rabbits.

It was proposed that CYP7A1 expression is suppressed through the gut-hepatic signaling pathway fibroblast growth factor (FGF) 15/19-fibroblast growth factor receptor 4, which is initiated by activation of farnesoid X receptor in the intestine rather than in the liver. The present study tested whether portal bile acid flux alone without ileal FGF19 could downregulate CYP7A1 expression in rabbits. A rabbit model was developed by infusing glycodeoxycholic acid (GDCA) through the splenic vein to bypass ileal FGF19. Study was conducted in four groups of rabbits: control; bile fistula + bovine serum albumin solution perfusion (BF); BF + GDCA (by portal perfusion); and BF + GDCA-f (by femoral perfusion). Compared with only BF, BF + GDCA (6 h portal perfusion) suppressed CYP7A1 mRNA, whereas BF + GDCA-f (via femoral vein) with the same perfusion rate of GDCA did not show inhibitory effects. Meanwhile, there was a decrease in ileal FGF19 expression and portal FGF19 protein levels, but an equivalent increase in biliary bile acid outputs in both GDCA perfusion groups. This study demonstrated that portal bile acid flux alone downregulated CYP7A1 expression with diminished FGF19 expression and protein levels, whereas the same bile acid flux reaching the liver through the hepatic artery via femoral vein had no inhibitory effect on CYP7A1. We propose that bile acid flux through the portal venous system may be a kind of "intestinal factor" that suppresses CYP7A1 expression.

Desmosterol in brain is elevated because DHCR24 needs REST for Robust Expression but REST is poorly expressed.

Cholesterol synthesis in the fetal brain is inhibited because activity of DHCR24 (24-dehydrocholesterol reductase) is insufficient, causing concentrations of the precursor desmosterol to increase temporarily to 15-25% of total sterols at birth. We demonstrate that failure of DHCR24 to be adequately upregulated during periods of elevated cholesterol synthesis in the brain results from the presence in its promoter of the repressor element 1 (RE1) nucleotide sequence that binds the RE1-silencing transcription factor (REST) and that REST, generally reduced in neural tissues, uncharacteristically but not without precedent, enhances DHCR24 transcription. DHCR24 and REST mRNA levels are reduced 3- to 4-fold in fetal mouse brain compared to liver (p < 0.001). Chromatin immunoprecipitation assays suggested that REST binds to the human DHCR24 promoter in the vicinity of the predicted human RE1 sequence. Luminescent emission from a human DHCR24 promoter construct with a mutated RE1 sequence was reduced 2-fold compared to output from a reporter with wild-type RE1 (p < 0.005). Silencing REST in HeLa cells resulted in significant reductions of DHCR24 mRNA (2-fold) and DHCR24 protein (4-fold). As expected, relative concentrations of Δ(24)-cholesterol precursor sterols increased 3- to 4-fold, reflecting the inhibition of DHCR24 enzyme activity. In contrast, mRNA levels of DHCR7 (sterol 7-dehydrocholesterol reductase), a gene essential for cholesterol synthesis lacking an RE1 sequence, and concentrations of HMGR (3-hydroxy-3-methyl-glutaryl-CoA reductase) enzyme protein were both unaffected. Surprisingly, a dominant negative fragment of REST consisting of just the DNA binding domain (about 20% of the protein) and full-length REST enhanced DHCR24 expression equally well. Furthermore, RE1 and the sterol response element (SRE), the respective binding sites for REST and the SRE binding protein (SREBP), are contiguous. These observations led us to hypothesize that REST acts because it is bound in close proximity to SREBP, thus amplifying its ability to upregulate DHCR24. It is likely that modulation of DHCR24 expression by REST persisted in the mammalian genome either because it does no harm or because suppressing metabolically active DHCR24 while providing abundant quantities of the multifunctional sterol desmosterol during neural development proved useful.

Associations of platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphisms with circulating PAF-AH levels and risk of coronary heart disease or blood stasis syndrome in the Chinese Han population.

The circulating level of platelet-activating factor acetylhydrolase (PAF-AH) is a novel biomarker to predict the presence of coronary heart disease. PAF-AH gene polymorphisms may be responsible for the variance of circulating PAF-AH levels in individuals. However, the association of PAF-AH gene polymorphisms with circulating PAF-AH levels and the susceptibility to coronary heart disease (CHD) remains unsolved. Blood stasis syndrome (BSS) of CHD is the most common type of TCM syndromes, and a previous study discovered its relationship with the elevated circulating PAF-AH levels. However, the association of gene polymorphisms and CHD with BSS is unclear at present. In this study, four polymorphisms (R92H, I198T, A379V, V279F) of the PAF-AH gene were genotyped in 570 CHD patients, of which 299 had BSS. In addition, 317 unaffected individuals from the same hospitals served as controls. Plasma PAF-AH levels were measured in 155 controls and 271 CHD patients selected randomly, including 139 CHD patients with BSS. In the Chinese Han population, plasma PAF-AH levels in CHD patients with BSS or without BSS were significantly higher (12.9 ± 6.5 and 11.1 ± 5.0 µM, respectively) than in controls (9.3 ± 5.2 µM); this difference still remained significant after adjustment for traditional risk factors or the inflammatory factors. The R92H polymorphism was highly related to the plasma PAF-AH levels and the risk of CHD, especially among patients with BSS, even with the adjustment for the effects of traditional factors. The I198T polymorphism was highly associated with risk of CHD with BSS, but was associated with neither the risk of CHD with no BSS nor with elevated plasma PAF-AH levels.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

[A controlled clinical study of vertebroplasty for the treatment of osteoporotic vertebral compression fractures after self-made spinal positioner and manual reduction].

OBJECTIVE: To explore clinical effect of manipulation reduction combined with vertebral plasty on osteoporotic compression fractures (OVCFs). METHODS: Totally 61 patients with OVCFs treated from January 2022 to March 2024 were randomly divided into self-made spinal locator positioning with manipulation reduction group (treatment group) and traditional Kirchner positioning group (control group). There were 30 patients in treatment group, including 4 males and 26 females, aged from 61 to 87 years old with an average of (73.61±7.17) years old;body mass index (BMI) ranged from 15.24 to 28.89 kg·m-2 with an average of (23.90±3.20) kg·m-2;bone mineral density T value ranged from -4.90 to -2.50 SD with an avergae of (-3.43±0.75) SD;fracture to operation time was 6.50 (4.00, 10.25) d;10 patients were gradeⅠ, 13 patients were gradeⅡ, and 7 patients were grade Ⅲ according to Genant classification of fracture compression. There were 31 patients in control group, including 7 males and 24 females, aged from 61 to 89 years old with an average of (73.63±8.77) years old;BMI ranged from 18.43 to 27.06 kg·m-2 with an average of (23.67±2.35) kg·m-2;bone mineral density T value ranged from -4.60 to -2.50 SD with an avergae of (-3.30±0.68) SD;fracture to operation time was 6.00 (3.00, 8.00) d;11 patients were gradeⅠ, 9 patients were gradeⅡ, and 11 patients were grade Ⅲ according to Genant classification of fracture compression. The puncture times, X-ray fluoroscopy times and puncture time between two groups were observed and compared. Visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and timed up and go test (TUGT) were observed and compared before operation, 3 d and 1 month after operation. RESULTS: All patients were followed up for 1 to 3 months with an average of (2.10±0.80) months. Puncture times, X-ray fluorosecopy times and puncture time in treatment group were 5.00(4.00, 6.00) times, (29.53±5.89) times and 14.83(12.42, 21.20) min, respectively, while those in control group were 7.00(6.00, 8.00) times, (34.58±5.33) times, 22.19(17.33, 27.01) min, treatment group was better than those of control group (P<0.05). There were no significant differences in preoperative VAS, JOA and TUGT between two groups(P>0.05). VAS, JOA and TUGT in both groups were significantly improved after opeation(P<0.05). On the third day after operation, JOA score of treatment group was 23.00 (20.75, 25.00), which was higher than that of control group 20.00(19.00, 23.00)(P<0.05). TUGT of treatment group was 6.26(5.86, 6.57) s, which was better than that of control group 6.90(6.80, 7.14) s (P<0.05). Bone cement leakage occurred with 1 patient in treatment group and 2 patients in control group. CONCLUSION: The optimal scheme of self-made spinal locators for locating descending verteboplasty combined with traditional Chinese medicine reduction manipulation for OVCF patients could reduce the number of intraoperative puncture times, shorten puncture times and reduce number of X-ray fluoroscopy times, and have advantages over the simple positioning of Kirschn's needle in restoring short-term lumbar function and standing and walking ability of postoperative patients.

Risk of Bleeding Following Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. Design, Setting, and Participants: This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. Exposures: NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. Main Outcomes and Measures: The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Results: Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. Conclusions and Relevance: In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

FGF15/19 protein levels in the portal blood do not reflect changes in the ileal FGF15/19 or hepatic CYP7A1 mRNA levels.

It has been proposed that bile acid suppression of CYP7A1 gene expression is mediated through a gut-liver signaling pathway fibroblast growth factor (FGF)15/19-fibroblast growth factor receptor 4 which is initiated by activation of farnesoid X receptor in the ileum but not in the liver. This study evaluated whether FGF15/19 protein levels in the portal blood reflected changes in FGF15/19 mRNA in the ileum. Studies were conducted in Sprague Dawley rats and New Zealand white rabbits fed regular chow (controls), supplemented with cholesterol (Ch) or cholic acid (CA). After feeding CA, ileal FGF15 mRNA increased 8.5-fold in rats and FGF19 rose 16-fold in rabbits associated with 62 and 75% reduction of CYP7A1 mRNA, respectively. Neither FGF15 nor FGF19 protein levels changed in the portal blood to correspond with the marked increase of FGF15/19 mRNA levels in the ileum or inhibited CYP7A1 expression in the liver. Further, in Ch-fed rats, CYP7A1 mRNA increased 1.9-fold (P < 0.001) although FGF15 mRNA levels in the ileum and portal blood FGF15 protein levels were not decreased. In Ch-fed rabbits, although FGF19 mRNA levels in the ileum and liver did not increase significantly, CYP7A1 mRNA declined 49% (P < 0.05). We were unable to find corresponding changes of FGF15/19 protein levels in the portal blood in rats and rabbits where the mRNA levels of FGF15/19 in the ileum and CYP7A1 in the liver change significantly.

Primary cardiac angiosarcoma with spontaneous ruptures of the right atrium and right coronary artery.

Primary tumors of the heart are rarely seen. Cardiac angiosarcomas are malignant tumors that almost always have a poor prognosis. Atrium rupture and coronary artery fistula are very rare complications of primary cardiac angiosarcoma. We describe a 57-year-old man suffering from primary cardiac angiosarcoma with spontaneous ruptures of the right atrium and right coronary artery (RCA). Theoretically, either of these ruptures invariably results in pericardial effusion and tamponade that is rare but potentially life threatening. In this instance, however, the patient might have developed fibrous adhesions resulted from previous bloody pericardial effusion. A massive pericardial effusion was localized, which consequently prevented cardiac tamponade and hemodynamic collapse. Echocardiography revealed the tumor progression leading to detectable infiltration of solid mass into the right atrial (RA) wall, which is close to RCA. And color Doppler displayed the flow into the pericardial cavity through a disrupted RA wall and perforated RCA. Echocardiography remains the primary method of choice for evaluation of cardiac masses.

[Detection and analysis of polymorphisms of 59571364 and 59912586 loci on X chromosome in fat-tail and thin-tail sheep flocks].

In order to analyze the correlation of tail fat deposition and two SNP loci on Ovis arise chromosome X and provide a theoretical basis for using molecular assisted selection technology in further low-fat sheep breeding, the breeds with extreme differences in tail types (Altay, Small Tail Han Sheep, Hu, Chinese Merino and Suffolk) were used to detect the polymorphisms of two SNP loci on X chromosome and the haplotypes with PCR-RFLP method. The results showed that the TT genotype at 59571364 locus and GG genotype at 59912586 locus were preponderant genotypes in thin-tailed Chinese Merino and Suffolk sheep flocks, while the percentage of the two genotypes in fat-tailed (fat-rmup) Altay and Hu flocks is less than 2%. Haplotype analysis showed that CA haplotype is the main haplotype, the percentage of CA is up to 55%, and the percentage of CA and TA haplotypes together was 88.33% in Altay sheep flock. These results suggest that there are great differences in the SNP distribution of the 59571364 and 59912586 loci among different tail-typed sheep flocks, which can be used as molecular markers in high or low fat sheep breeding.

[Correlation analysis between polymorphism of the 59383635th locus on X chromosome and fat-tail trait in sheep].

Fat tail or fat rump is one of essential traits for surviving in harsh environments, and the mechanism of fat deposition and its inheritable characters in sheep are still unclear. Therefore, the 59383635th locus on X chromosome in our unpublished chip data was chosen as candidate SNP, PCR-SSCP method was used to detect genotypes in five sheep breeds which have extreme differences in tail types (Altay, Small Tail Han Sheep, Hu, Chinese Merino and Suffolk), and the mathematical model was employed to analyze the correlation between the polymorphism and the trait of fat tail or fat rump. The results in this study showed that the high frequency of allele T exists in Altay flock, and the frequency of allele C appears to be particularly high in the thin tail sheep breeds. The result of mathematical model showed that the ratio of T/C increased exponentially with the increase of phenotype score. These results suggest that there is a big difference in the SNP distribution between fat tail (rump) and thin tail sheep populations, and the SNP can be used as an ideal molecular marker in high-fat or low-fat sheep breeding. However, the biological function of the SNP remains to be further studied.

[Relative quantification of mRNA transcription of Cry1 in different tissues of sheep in oestrous cycle by real-time quantitative PCR].

Studies have shown that clock gene Cry1 may have important roles in the endocrine process of seasonal reproduction in mammals. In this study, Duolang sheep (non-seasonal reproduction sheep breed) and Chinese Merino (seasonal reproduction sheep breed) were used to determine the expression change of Cry1 in hypothalamus-pituitary-ovary axis in different stage of estrous cycle by quantitative real-time PCR. The results showed that the Cry1 mRNA was expressed in all tested tissues, in which the expression levels in pineal gland and thyroid gland were higher than in other tissues. As far as different sheep breeds were concerned, the tissue expression profiles of Cry1 at different stage of estrous cycle were broadly similar. Besides hypothalamus, the expression levels of Cry1 in ovary, uterus, pineal gland, pituitary gland, and thyroid gland were all reached to peak in proestrus. The differences of expression change extent for Cry1 in vary, uterus, pineal gland, and pituitary gland in proestrus and oestrus were significant between different sheep breeds. The results suggested that Cry1 may play roles in switching on the estrus and seasonal reproduction.