Digoxin Ameliorates Glymphatic Transport and Cognitive Impairment in a Mouse Model of Chronic Cerebral Hypoperfusion / 神经科学通报·英文版

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.

Current developmental status of non-surgical treatment of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality in clinical practice. With the development of imaging and interventional techniques, transcatheter arterial chemoembolization and local ablation are more and more widely used for treatment and can even achieve a similar effect as surgery in the treatment of some types of early-stage HCC. In addition, precision medicine and biomedicine have also developed vigorously; radiochemotherapy is more accurate and effective in the treatment of HCC, and molecular targeted therapy, immunotherapy, and gene therapy have become the directions for breakthrough in the future. This article reviews the latest advances in the non-surgical treatment of HCC.

Small RNA interference-mediated gene silencing of TREK-1 potassium channel in cultured astrocytes / 华中科技大学学报（医学）（英德文版）

This study was aimed to examine the effect of TREK-1 silencing on the function of astrocytes. Three 21-nucleotide small interfering RNA (siRNA) duplexes (siT1, siT2, siT3) targeting TREK-1 were constructed. Cy3-labeled dsRNA oligmers were used to determine the transfection efficiency in cultured astrocytes. TREK-1-specific siRNA duplexes (siT1, siT2, siT3) at the optimal concentration were transfected into cultured astrocytes, and the most efficient siRNA was identified by the method of immunocytochemical staining and Western blotting. The proliferation of astrocytes tranfected with TREK-1-targeting siRNA under hypoxia condition was measured by fluorescence-activated cell sorting (FACS). The results showed that TREK-1 was expressed in cultured astrocytes. The dsRNA oligmers targeting TREK-1 could be transfected efficiently in cultured astrocytes and down-regulate the expression of TREK-1 in astrocytes. Moreover, the down-regulation of TREK-1 in astrocytes contributed to the proliferation of astrocytes under hypoxia condition as determined by cell cycle analysis. It was concluded that siRNA is a powerful technique that can be used to knockdown the expression of TREK-1 in astrocytes, which helps further investigate the function of TREK-1 channel in astrocytes under physicological and pathological condition.

Small RNA interference-mediated gene silencing of TREK-1 potassium channel in cultured astrocytes / 华中科技大学学报（医学）（英德文版）

This study was aimed to examine the effect of TREK-1 silencing on the function of astrocytes. Three 21-nucleotide small interfering RNA (siRNA) duplexes (siT1, siT2, siT3) targeting TREK-1 were constructed. Cy3-labeled dsRNA oligmers were used to determine the transfection efficiency in cultured astrocytes. TREK-1-specific siRNA duplexes (siT1, siT2, siT3) at the optimal concentration were transfected into cultured astrocytes, and the most efficient siRNA was identified by the method of immunocytochemical staining and Western blotting. The proliferation of astrocytes tranfected with TREK-1-targeting siRNA under hypoxia condition was measured by fluorescence-activated cell sorting (FACS). The results showed that TREK-1 was expressed in cultured astrocytes. The dsRNA oligmers targeting TREK-1 could be transfected efficiently in cultured astrocytes and down-regulate the expression of TREK-1 in astrocytes. Moreover, the down-regulation of TREK-1 in astrocytes contributed to the proliferation of astrocytes under hypoxia condition as determined by cell cycle analysis. It was concluded that siRNA is a powerful technique that can be used to knockdown the expression of TREK-1 in astrocytes, which helps further investigate the function of TREK-1 channel in astrocytes under physicological and pathological condition.

Effects of Ischemia and Anoxia on Cell Activation and Cell Cycle of Cultured Astrocytes in vitro / 华中科技大学学报（医学）（英德文版）

To examine the effects of ischemia and anoxia on cell activation and cell cycle of astrocytes in vitro, the cell cycles and the proliferation of astrocytes in different time points after ischemia and anoxia were studied by flow cytometry and BrdU labeling and the expression of GFAP and cyclin D1 was detected by the fluorescence immunochemistry. After ischemia and anoxia in vitro,the astrocytes in S phase were significantly increased as compared with those in the normal group and the proliferating ability of the astrocytes was highest 6 h after the treatment as revealed by BrdU pulse labeling, but the astrocytes in S phase and proliferating ability were decreased after 6 h.At the early stages of ischemia and anoxia, the positive staining intensity of GFAP was increased,peaked at 6th h, while 12 h after the ischemia and anoxia, the positive staining intensity of GFAP became weak, and the expression of cyclin D1 was gradually increased after the ischemic and anoxic damage. It is concluded that astrocytes are activated to proliferate and enter new cycle events by ischemia and anoxia, and cyclin D1 is implicated in the proliferation and repair of astrocytes. The cell cycle events are closely associated with the proliferation and activation of astrocytes.

Effects of ischemia and anoxia on cell activation and cell cycle of cultured astrocytes in vitro / 华中科技大学学报（医学）（英德文版）

To examine the effects of ischemia and anoxia on cell activation and cell cycle of astrocytes in vitro, the cell cycles and the proliferation of astrocytes in different time points after ischemia and anoxia were studied by flow cytometry and BrdU labeling and the expression of GFAP and cyclin D1 was detected by the fluorescence immunochemistry. After ischemia and anoxia in vitro, the astrocytes in S phase were significantly increased as compared with those in the normal group and the proliferating ability of the astrocytes was highest 6 h after the treatment as revealed by BrdU pulse labeling, but the astrocytes in S phase and proliferating ability were decreased after 6 h. At the early stages of ischemia and anoxia, the positive staining intensity of GFAP was increased, peaked at 6th h, while 12 h after the ischemia and anoxia, the positive staining intensity of GFAP became weak, and the expression of cyclin D1 was gradually increased after the ischemic and anoxic damage. It is concluded that astrocytes are activated to proliferate and enter new cycle events by ischemia and anoxia, and cyclin D1 is implicated in the proliferation and repair of astrocytes. The cell cycle events are closely associated with the proliferation and activation of astrocytes.

Expression of aquaporin-1 in the human peritoneum and the effect of peritoneal dialysis on its expression / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the expression of aquaporin-1 (AQP1) in the human peritoneum and to evaluate the effect of peritoneal dialysis (PD) on its expression.</p><p><b>METHODS</b>Peritoneal biopsies were obtained from normal subjects (n = 10), uremic nondialysis patients (n = 12) at catheter insertion and PD patients (n = 10) at the time of catheter removal, reinsertion or renal transplantation. Western blot, immuno-histochemical staining and reverse transcript-polymerase chain reaction (RT-PCR) techniques were used to investigate AQP1 expression.</p><p><b>RESULTS</b>All peritoneal samples expressed AQP1 at both mRNA and protein levels. Western blot revealed a major band at 28 kD as well as more diffuse bands between 35 and 50 kD. The 28 kD band represents the nonglycosylated form of the protein while the 35 - 50 kD bands correspond to glycosylated AQP1. Immunohistochemical staining found the positive deposits were distributed in the mesothelial cells, endothelial cells of capillaries, venules and small veins, whereas no signal was detected in the arterioles. Semi-quantitative analysis showed that AQP1 expression was remarkably stable in all samples, whatever their origin (P > 0.05).</p><p><b>CONCLUSIONS</b>Our findings suggested that AQP1 is the molecular counterpart of an ultra small pore during PD. Secondly, the peritoneal mesothelial cell might also be involved in peritoneal transcellular water transport. As regards whether or not the structural or distributional alterations of AQP1 in the peritoneum may be more obviously expressed during PD, further study is needed.</p>

The study of IL-1?,TNF-? and IL-6 gene expression and plasma levels on hemodialysis equipped with reused dialyzer / 中华肾脏病杂志

RT-PCR and in situ hybridization were observed during dialyzer reuse. Results Every plasma cytokine level was decreased during reuse compared with first use dialyzer, but no significant difference was found between them. The levels of gene expression of IL-1?、TNF-? and IL-6 were different from the first use significantly. Conclusion If effective dialysis volumn was maintained, formaldehyde as disinfectant on reprocessing the dialyzer may amilorate membrane bio-compatibility. It would be benificial to decrease appearance of long term hemodialysis -related complications.

Morphological changes of human peritoneum during peritoneal dialysis / 中华肾脏病杂志

Objective To investigate the morphological changes of peritoneum during peritoneal dialysis (PD) and elucidate the possible mechanism of its functional deterioration. Methods Peritoneal biopsies were obtained from normal subjects( n = 10), uremic predialysis patients( n = 12) at catheter insertion and PD patients ( n = 10) at the time of catheter remove or reinsertion or renal transplantation, peritoneal morphology was studied by light microscopy, scanning electron microscopy and transmission electron microscopy. Results Normal peritoneal membrane consisted of a monolayer of mesothelial cells on a basement membrane, and a layer of connective tissue containing cells, blood vessels, lymphatic vessels and so on. Mesothelial cells were polygonal, often elongated, and had numerous microvilli on their luminal surface. Sometimes the microvilli ended with roundish formation or resembled a corona. There were lots of oval or roundish pinocytotic vesicles in the cytoplasm of mesothelial cell. Submesothelial connective tissue contained many collagen and elastic fibers. The peritoneal morphology of uremic predialysis patients was similar to that of normal subjects. But significant abnormalities of peritoneal morphology were observed in PD patients and the changes were progressive. Microvilli were the first site of damage, including microvilli shortening, gradual reduction in number and following total disappearance. Then mesolhelial cell detachment from basement membrane and total disappearances were found. Finally the peritoneal membrane only consisted of submesothelial connective tissue denudation of cells. Conclusions PD can modify peritoneal morphology and structure. The morphological change is progressive and might be one of the important causes of peritoneal failure. Peritoneal biopsy can provide lots of valuable informations about the impact of PD, and thus further study on the relationship between peritoneal structure and its function is very useful for understanding of the physiopathology of peritoneum during PD.

Study of IL-1?, TNF-? and IL-6 gene expression for peripheral blood mononudear cells in non-dialysis uremic patients / 中华肾脏病杂志

To determine whether uremia per se can activate peripheral blood mononuclear cells (PBMCs). Methods Maintained hemodialysis patients with cuprophane, non-dialysis uremic patients and healthy volunteers were selected to investigate IL-1?、 TNF-? and 11,6 mRNA in PBMCs by RT-PCR and cells in situ hybridization. Results IL-1?,TNF-? and IL-6 mRNA in PBMCs were undetected in healthy volunteers, but these cytokine gene expression were detected in hemodialysis patients and non-dialysis uremic patients. IL-1?、TNF-? and IL-6 mRNA level was lower in non-dialysis uremic patients than that in hemodialysis patients. Conclusion Uremia per se or its related factors may activated PBMCs and the preactivation of PBMCs might be associated with the body resistance against infection in uremic patients.