Metastasia Lesion of Gestation Trophoblastic Tumor in Abdominopelvic Cavity Diagnosed by Sonographic and Doppler Imaging

Objective: The purpose of this study was to review clinical data of metastasia lesion of gestation trophoblastic tumor (GTT) in abdominopelvic cavity by color Doppler ultrasound. Subjects and Methods: A retrospective analysis of 13 cases of GTT in China was performed. Clinical appearances, serum human chorionic gonadotropin (hCG) levels, sonographic findings, Doppler waveforms, and patient outcomes were followed up. Color Doppler ultrasound was performed to diagnose the presence of GTT, detect metastasia lesion in abdominopelvic cavity, assess disease recurrence, and monitor the efficacy of chemotherapy. Results: Of the 13 patients with GTT, 4 had choriocarcinoma which 3 cases occurred after an abortion, 1 after a year of dilation and suction evacuation for the hydatidform mole. Metastasia lesion in abdominopelvic cavity was detected by color Doppler ultrasound in all cases of choriocarcinoma, among which the metastasia lesion were found at uterine fundus, near uterus, colon and cystic vascular space near the uterus, repectively. 9 cases with an invasive hydatidiforn mole (IHM) occurred after one to three months of dilation and suction evacuation for the hydatidform mole, consistant with the hCG levels markedly elevating. Metastasia lesion in abdominopelvic cavity was also detected by color Doppler ultrasound besides invasive lesion in uterine muscular layer in all cases of IHM, among which 3 cases showed metastasia lesion in cystic vascular space near the uterus, 2 cases were detected in side wall of pelvic cavity, while the rest were found in abdominal cavity, right kidney, colon and near uterus, respectively. Meanwhile, the image of metastasia lesion with IHM was similar to choriocarcinoma’s. And the reticular structure, the cystic vascular space and solid lesion may be showed by ultrasound. The metastasia lesion had abundant flow. Doppler waveforms showed resistive indices of 0.34 (SD 0.07) for metastasia lesion. There was the same lower-impedance as invasive lesion in uterine muscular layer. Except an IHM with the renal metastasia lesion having been followed, abnormal sonographic and Doppler findings in other metastasia disease all disappeared after surgical operation or chemotherapy were successful. Conclusions: Sonography and Doppler imaging were helpful in detecting metastasia lesion in abdominopelvic cavity, and in following the effectiveness of chemotherapy. And it should be taken full examination for GTT by Color Doppler ultrasound in order to avoid mistake.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species

The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Profibrogenic macrophage-targeted delivery of mitochondrial protector via exosome formula for alleviating pulmonary fibrosis

Pulmonary fibrosis(PF)is a devastating lung disease with limited treatment options.During this pathological process,the profibrogenic macrophage subpopulation plays a crucial role,making the characterization of this subpopulation fundamentally important.The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass(Mø^(mitohigh))and fibrosis.Among the Mø^(mitohigh)subpopulation of CD206^(+)M2,characterized by higher expression of dynamin 1-like(Drp1),as determined by flow cytometry and RNA-seq analysis,a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics.A pathfinder exosome called“exosome^(MMP19)(Exo^(MMP19))”,was constructed to display matrix metalloproteinase-19(^(MMP19))on the surface to locally break down the excessive extracellular matrix(ECM)in the fibrotic lung.A therapeutic exosome called“exosome therapeutics(Exo^(Tx))”,was engineered to display D-mannose on the surface while encapsulating siDrp1 inside.Prior delivery of Exo^(MMP19)degraded excessive ECM and thus paved the way for Exo^(Tx)to be delivered into Mø^(mitohigh),where Exo^(Tx)inhibited mitochondrial fission and alleviated PF.This study has not only identified Mø^(mitohigh)as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.

Measurement of left ventricular fluid dynamic parameters in healthy Chinese adults based on echocardiographic vector flow mapping

To the Editor:As we concerdered that there was barely any widely representative,recognized,and standardized echocardiographic vector flow mapping(VFM)method has been established for the observation and measurement of the blood flow in cardiac cavities in clinical practice,and there were no commonly accepted normal reference values for Chinese adults have been obtained till now,hindering the further promotion and application of this technology in clinical practice.Establishing normal reference values for echocardiographic VFM that can be widely accepted in clinical practice is of great significance for determining the normal or abnormal fluid dynamic status in the left ventricle(LV)chamber.

Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension

Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure,and its physiopathologic mechanism is still not fully understood.We here aimed to explore whether extracellular vesicle(EV)mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension.We here revealed that the arterial endothelial cells robustly secreted EV,which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells(SMC).Under hypertension,the EV secretion increased and the miRNA profile changed significantly mainly due to the raised mechanical force and subsequent enhanced reactive oxygen species generation.Among the miRNA cargos in the EV,miR-320d/423-5p were found increased most significantly.In vivo delivery of miR-320d/423-5p mimics via engineered EV increased their expression in arterial vessels,recapitulating the phenotype in hypertension.In contrast,therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV alleviated the phenotype in spontaneous hypertension rat model.Together,we have found that the injured endothelium due to the raised mechanical force in hypertension contributes to the arterial wall remodeling via the secreted EV.Our study has not only provided novel insights on the mechanism of hypertension associated blood vessel wall remodeling,but also shed light on therapeutic intervention of hypertension associated vascular diseases.

Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE^(-/-) mice

Atherosclerosis is characterized by inflammation in the arterial wall,which is known to be exacerbated by diabetes.Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis.In this study,we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout(ApoE^(-/-))mice,in which increased expression of long-chain acyl-CoA synthetase 1(Acsl1)in macrophages played an important role.Knockdown of Acsl1 in macrophages(Mφ^(shAcsl1))reprogrammed macrophages to an anti-inflammatory phenotype,especially under hyperglycemic conditions.Injection of Mφ^(shAcsl1) reprogrammed macrophages into streptozotocin(STZ)-induced diabetic ApoE^(-/-) mice(ApoE^(-/-)+STZ)alleviated inflammation locally in the plaque,liver and spleen.Consistent with the reduction in inflammation,plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages.Taken together,our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice,possibly by promoting inflammation.Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.

Chinese Ethics Review System and Chinese Medicine Ethical Review:Past,Present,and Future

The Chinese medical ethics committee and the ethical review system have made the following achievements： （1） enabled the institutionalization of medical ethics, （2） carried out the ethics review of Chinese medicine （CM） and integrative medicine extensively, （3） trained a large number of ethical professionals, （4） supported and protected the interests of patients and subjects, and （5） ensured the correct direction of biological research and provided ethical defense for the publication of its results. However, at the same time, they are also faced with some new problems and difficulties that need to be resolved in the following ways： （1） to refine the relevant rules of ethical review, （2） to develop the relevant standards of the CM and integrative medicine ethical review, （3） to enhance the independence and authority of ethics committee, （4） to emphasize innovation and to discover and solve new problems, and （5） to increase international exchanges and improve relevant research.

HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy

Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy.In this study,we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment.Epigenetically silencing of Hif1αvia histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system,in which histone H3 methylase EZH2 was recruited to the promoter region specifically.The Hif1αsilenced macrophage,namely HERM(Hif1αEpigenetically Repressed Macrophage)manifested as inheritable tumor suppressing phenotype.In the subcutaneous B16-F10 melanoma syngeneic model,intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one,reducing tumor burden and prolonging overall survival.Additionally,HERMs therapy remarkably inhibited tumor angiogenesis.Together,our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment,but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages.