Novel TrueVue series of 3D echocardiography: Revealing the pathological morphology of congenital heart disease.

Aims: This study explored the advantages and limitations of novel series of three-dimensional (3D) echocardiographic techniques and summarized their application methods for congenital heart diseases (CHDs). Method and result: Two-dimensional (2D), traditional 3D echocardiography, and TrueVue plus light and/or Glass novel 3D technologies were performed on 62 patients with CHD, and a clinical survey was designed to judge whether the novel 3D images were more helpful for understanding the cardiac condition and guide treatment than traditional 3D images. TrueVue increased the visual resolution and simulated the true texture of cardiac tissue, significantly improving the display ability of abnormal anatomical structures in CHDs. TrueVue Glass displayed the blood channel and the internal structure of cardiac cavity more intuitively, indicating a new observation aspect not shown by conventional echocardiography. The clinical survey results showed that the new 3D imaging methods effectively increased the diagnostic confidence of echocardiographers, enabled surgeons to better understand the details of lesions, promoted efficient communication, and improved the confidence of both doctors and patients in treatment. Conclusion: The combined application of TrueVue, TrueVue Light, and TrueVue Glass more closely simulated real anatomical features, showed more comprehensive and subtle blood flow in the lumen, not only increased the visual effect but also provided more useful diagnostic information, improved the accuracy of evaluation and treatment of CHD when compared to traditional imaging techniques, indicating that this combined application has significant clinical value.

Remodeling Chondroitin-6-Sulfate-Mediated Immune Exclusion Enhances Anti-PD-1 Response in Colorectal Cancer with Microsatellite Stability.

Metastatic microsatellite-stable (MSS) colorectal cancer rarely responds to immune checkpoint inhibitors (ICI). Metabolism heterogeneity in the tumor microenvironment (TME) presents obstacles to antitumor immune response. Combining transcriptome (The Cancer Genome Atlas MSS colorectal cancer, n = 383) and digital pathology (n = 96) analysis, we demonstrated a stroma metabolism-immune excluded subtype with poor prognosis in MSS colorectal cancer, which could be attributed to interaction between chondroitin-6-sulfate (C-6-S) metabolites and M2 macrophages, forming the "exclusion barrier" in the invasive margin. Furthermore, C-6-S derived from cancer-associated fibroblasts promoted co-nuclear translocation of pSTAT3 and GLI1, activating the JAK/STAT3 and Hedgehog pathways. In vivo experiments with C-6-S-targeted strategies decreased M2 macrophages and reprogrammed the immunosuppressive TME, leading to enhanced response to anti-PD-1 in MSS colorectal cancer. Therefore, C-6-S-induced immune exclusion represents an "immunometabolic checkpoint" that can be exploited for the application of combination strategies in MSS colorectal cancer ICI treatment.

Rare double orifice mitral valve malformation associated with bicuspid aortic valve in Turner syndrome: diagnosed by a series of novel three-dimensional echocardiography and literature review.

BACKGROUND: Patients with both double orifice mitral valve (DOMV) and bicuspid aortic valve (BAV) malformation are rare. Although DOMV or BAV can be detected in some genetic syndromes, it has not been reported to simultaneously appear in Turner syndrome (TS). TrueVue, TouchVue, and TrueVue Glass are the latest technologies in advanced three-dimensional echocardiography (3DE), which is an important information supplement to two-dimensional echocardiography (2DE) for the diagnosis of congenital cardiac malformations. Herein we report the novel use of the above-mentioned technologies in the diagnosis and evaluation of a rare, combined valve malformation. Meanwhile, we also reviewed the literature for cases involving both DOMV and BAV and their association with various genetic syndromes. CASE PRESENTATION: We present the case of a 5-year-old girl diagnosed with TS because of a developmental delay. DOMV and BAV were found through echocardiographic examination. Three-dimensional transthoracic echocardiography as well as a series of novel advanced techniques were applied to clearly display the spatial structure of all tiers of the mitral valve apparatus, aortic valve, and arch to facilitate an accurate diagnosis. CONCLUSIONS: This is the first case in which both DOMV and BAV were associated with TS. Innovative TrueVue and TrueVue Glass offer unprecedented photographic stereoscopic images, while TouchVue technology greatly improved the ultrasonic diagnostic workflow and the diagnostic performance of rare valve malformations by adding virtual light sources to display realistic light-shadow effects.

Case Report: Management of a 10-Year-Old Patient Who Presented With Infective Endocarditis and Stanford Type A Aortic Dissection.

A 10-year-old girl presented with a chief complaint of cyclic vomiting since the last 12 h and chest pain since the last 6 h. She was diagnosed with Stanford type A aortic dissection. Intraoperatively, the aortic valve was found to be bi-lobed, and infective endocarditis associated with aortic valve perforation and rupture of the aortic sinus aneurysm, was also observed. Therefore, she underwent aortic valve replacement due to an enlarged aortic root and aortic sinus repair. The perioperative recovery was good. A large amount of bloody pericardial effusion was found in this child pre-operatively. Therefore, early surgical intervention was necessary. Acute aortic dissection rarely occurs in children. There are no clinical guidelines for the management of pediatric aortic dissection. However, if a large pericardial effusion exists, emergency surgery is necessary and effective. The treatment of the valve should be based on the actual situation. It is best to give priority to valve molding, although valve replacement is required in the majority of cases for infective endocarditis.

Melatonin attenuates diabetic cardiomyopathy and reduces myocardial vulnerability to ischemia-reperfusion injury by improving mitochondrial quality control: Role of SIRT6.

Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high-fat diet-streptozotocin-induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, and decreased myocardial SIRT6 and AMPK-PGC-1α-AKT signaling. 16 weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia-reperfusion (MI/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re-activating SIRT6 and AMPK-PGC-1α-AKT signaling. After the induction of diabetes, adeno-associated virus carrying SIRT6-specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin-induced AMPK-PGC-1α-AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long-term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI/R injury through preserving mitochondrial quality control. Melatonin membrane receptor-mediated SIRT6-AMPK-PGC-1α-AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia-reperfusion injury in diabetic patients.

ALK-TPM3 rearrangement in adult renal cell carcinoma: a case report and literature review.

BACKGROUND: Translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) is a rare subtype of adult renal cell carcinoma (RCC) reported in recent years. It was recognized as a group of emerging /provisional RCC in the latest World Health Organization's classification (2016). CASE PRESENTATION: A new Chinese case of ALK-tRCC was reported. The patient was a 58-year-old man with a tumor in kidney. The tumor was composed of sheets of large cells with abundant eosinophilic cytoplasm and indistinct cell borders but conspicuous intracytoplasmic vacuoles. The nuclei were enlarged with a nucleolar of grade 4. Immunohistochemically, tumor cells were diffusely positive for PAX8, keratin (AE1/AE3), epithelial membrane antigen (EMA) and CK7. Fluorescent in situ hybridization (FISH) showed a rearrangement of ALK in tumor cells. CONCLUSION: ALK-tRCC is a rare subtype of adult RCC. Its diagnosis is very difficult because the histological spectrum is very wide. We suggested that RCCs should be screened for ALK expression by immunohistochemistry (IHC) for the patient might benefit from ALK inhibitors therapy.

Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming.

Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis.

Overexpression of osteopontin in hepatocellular carcinoma and its relationships with metastasis, invasion of tumor cells.

Osteopontin (OPN) plays an important role in metastasis and relapse of human cancer. However, the whole story of OPN relating to cancer has been far from clear untill now. To investigate the expression of OPN in hepatocellular carcinoma (HCC) and its relationships with recurrence and metastasis of HCC, normal and malignant liver tissues from patients with HCC were analyzed using immunohistochemical staining. OPN expression was inhibited by small interfering RNA (siRNA) in HCC cells lines, and then colony formation and matrigel invasion were examined. The results showed that expression of OPN was associated with metastasis of HCC with a positive rate of OPN in the tissue of HCC (70.00%), which was highly more obvious than those in paracarcinoma tissue and normal liver tissue (P < 0.01). In HCC cell lines, OPN depletion could reduce formed colony and metastasizing numbers in vitro. In conclusion, Expression of OPN in the tissue of HCC is related to metastasis or metastases. Specific siRNA could decrease expressions of OPN at both mRNA and protein levels, and abates the invasiveness of hepatocellular carcinoma cells, suggesting that OPN might be a promising agent for treatment of metastasis and recurrence of HCC.

[Nephrotoxicity of tacrolimus and preventive effect of diltiazem: experiment with rats].

OBJECTIVE: To study the nephrotoxicity tacrolimus (FK506) at the therapeutic dose the preventive effect of diltiazem (Dil), a calcium antagonist against the FK506-induced pathological changes. METHODS: 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: cyclosporine A (CsA) group, undergoing treatment of CsA at the therapeutic dose after kidney transplantation (25 mg x kg(-1) x d(-1)) for 4 weeks, FK506 group treated with FK506 (0.8 mg x kg(-1) x d(-1)), FK506 + Dil group treated with FK506 (0.8 mg x kg(-1) x d(-1)) and Dil at the dose of 8 mg x kg(-1) x d(-1), and control group. Four weeks later body weight was measured and 24 h urine sample was collected. Then the rats were killed. Their kidneys underwent light and transmission electron microscopy. RESULTS: The body weight ad weight gain, and the weights of both kidney of the CsA group were all significantly lower than those of the other 3 groups (all P < 0.05), and there were not significant differences in there parameters among the other 3 groups. The serum creatinine levels of the FK506 and CsA groups were (36.0 +/- 2.6) and (34.2 +/- 4.5) micromol/L respectively, both significantly higher than those of the FK506 + Dil and control groups [(28.5 +/- 2.1) and (29.2 +/- 3.428) micromol/L respectively, all P < 0.05], however, there was no significant difference between the FK506 + Dil and control groups. The creatinine clearance rate of the FK506 and CsA groups were (0.63 +/- 0.45) and (0.58 +/- 0.39) ml x min(-1) x 100 g(-1) respectively, significantly lower than those of the FK506 + Dil and control groups [(1.55 +/- 0.91) and (1.02 +/- 0.62) mlxmin(-1) x 100 g(-1) respectively, all P < 0.05]. Pathological examination showed epithelial cell cloudy swelling and vacuolization and interstitial fibrosis in the renal tubules, mitochondria swelling and vacuolization in renal tubular epithelial cells, renal arteriole hyalinization, and foot cell conjugation glomerulus, mitochondria swelling and vacuolization in the FK506 and CsA groups, and such changes were relatively mild in the FK506 + Dil group. CONCLUSION: FK506 at renal transplantation therapeutic dose, as well as CsA, induces pathological changes in renal tissues and ultrastructural organization. Dil is able to prevent FK506-induced these pathological changes.

[Prevention of diltiazem in tacrolimus-induced nephrotoxicity: experiment with rats].

OBJECTIVE: To study the nephrotoxicity induced by first oral administration of tacrolimus (FK506) and the prevention of diltiazem (Dil). METHODS: 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: control (n = 6), cyclosporine A (CsA) group (receiving CsA 25 mg.kg(-1).d(-1) so as to develop CsA-induced nephropathy model), FK506 group (receiving FK506 0.8 mg.kg(-1).d(-1), the common renal transplantation therapeutic dose, so as to develop FK506-induced nephropathy model), FK506 + Dil group (receiving CsA 0.8 mg.kg(-1).d(-1) and Dil 8 mg.kg(-1).d(-1)), and control group. Four weeks later body weight was measured, blood samples were collected to examine the creatinine, urea nitrogen, and uric acid, and urine samples were collected to examine the 24 h urine protein, uric acid, and creatinine. Then the rats were killed with their kidneys taken out to undergo histopathological examination. RESULTS: The urine creatinine levels of the CsA and FK506 groups were significantly lower than that of the control group (both P < 0.05), however, there was no significant difference in urine creatinine between the FK506 + Dil group and control group. The blood creatinine levels of both CsA and FK506 groups were significantly higher than those of the FK506 + Dil group and control group (all P < 0.05), however, there was no significant difference in blood creatinine between the FK506 + Dil group and control group. The urea nitrogen level of the CsA group was significantly higher than those of the other 3 groups (all P < 0.05). The creatinine clearance rates of the CsA and FK506 groups were both significantly lower than that of the control group (both P < 0.05), and the creatinine clearance rate of the FK506 + Dil group was between those of the FK506 group and control group, however, with significant differences with both of them. Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells in the CsA and FK506 groups. However, the pathological changes of the FK506 + Dil group were remarkably milder in comparison with these 2 groups. CONCLUSION: FK506 and CsA at the renal transplantation therapeutic dose induce nephrotoxicity. Diltiazem prevents FK506-induced nephrotoxicity.