A glaucoma micro-stent with diverging channel and stepped shaft structure based on microfluidic template processing technology.

BACKGROUND: Minimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted. RESULTS: The stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment. CONCLUSIONS: In summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma.

Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip.

The function and susceptibility of various drugs are tested with renal proximal tubular epithelial cells; yet, replicating the morphology and kidneys function using the currently available in vitro models remains difficult. To overcome this difficulty, in the study presented in this paper, a device and a three-layer microfluidic chip were developed, which provides a simulated environment for kidney organs. This device includes two parts: (1) microfluidic drug concentration gradient generator and (2) a flow-temperature controlled platform for culturing of kidney cells. In chip study, renal proximal tubular epithelial cells (RPTECs) and peritubular capillary endothelial cells (PCECs) were screened with the drugs to assess the drug-induced nephrotoxicity. Unlike cells cultured in petri dishes, cells cultured in the microfluidic device exhibited higher performance in terms of both cell growth and drug nephrotoxicity evaluation. It is worth mentioning that a significant decrease in cisplatin-induced nephrotoxicity was found because of the intervention of cimetidine in the microfluidic device. In conclusion, the different in the cell performance between the microfluidic device and the petri dishes demonstrates the physiological relevance of the nephrotoxicity screening technology along with the microfluidic device developed in this study. Furthermore, this technology can also facilitate the development of reliable kidney drugs and serve as a useful and efficient test-bed for further investigation of the drug nephrotoxicity evaluation.

Poly(ethylene glycol)-grafted cyclic acetals based polymer networks with non-water-swellable, biodegradable and surface hydrophilic properties.

Cyclic acetals based biomaterial without acidic products during hydrolytic degradation is a promising candidate for tissue engineering applications; however, low hydrophilicity is still one limitation for its biomedical application. In this work, we aim to achieve non-water-swellable cyclic acetal networks with improved hydrophilicity and surface wettability by copolymerization of cyclic acetal units based monomer, 5-ethyl-5-(hydroxymethyl)-ß,ß-dimethyl-1, 3-dioxane-2-ethanol diacrylate (EHD) and methoxy poly(ethylene glycol) monoacrylate (mPEGA) under UV irradiation, to avoid swelling of conventional hydrogels which could limit their applicability in particular of the mechanical properties and geometry integrity. Various EHD/mPEGA networks were fabricated with different concentrations of mPEGA from 0 to 30%, and the results showed photopolymerization behavior, mechanical property and thermal stability could not be significantly affected by addition of mPEGA, while the surface hydrophilicity was dramatically improved with the increase of mPEGA and could achieve a water contact angle of 37° with 30% mPEGA concentration. The obtained EHD/mPEGA network had comparative degradation rate to the PECA hydrogels reported previously, and MTT assay indicated it was biocompatible to L929 cells.

Microvascular damage is involved in the pathogenesis of heroin induced spongiform leukoencephalopathy.

OBJECTIVE: To investigate whether microvascular damage is involved in the pathogenesis of heroin induced spongiform leukoencephalopathy (HSLE). METHODS: The brain tissues were collected from 4 HSLE patients and 5 controls and then fixed in 4% paraformaldehyde. The frontal lobe, corpus callosum and cerebellum were separated. The expressions of myelin base protein (MBP) and CD34 were detected by immunohistochemistry. TUNEL staining was applied to detect cell apoptosis. The correlation between microvascular changes and pathological vacuoles was evaluated. RESULTS: No obvious abnormalities were found in the brain of controls. Immunohistochemistry for MBP showed the collapse and fracture of myelin sheath and vacuole formation in the subcortical white matter, corpus callosum, and cerebellar white matter of HSLE patients. TUNEL staining showed the number of apoptotic cells in the cerebellar white matter and corpus callosum of HSLE patients was significantly higher than that in controls (F = 389.451, P < 0.001). Masson's trichrome staining revealed vacuolar degeneration in the cerebral white matter of HSLE patients, and the vacuoles were distributed around the microvessels. Immunohistochemistry revealed CD34 positive cells were seldom found besides the vessels in the cerebellar white matter and corpus callosum of HSLE patients, but a variety of CD34 positive cells was found in the vascular wall of controls (F = 838.500, P < 0.001). CONCLUSION: Apoptosis of oligodendrocytes may be related to the HSLE. Cerebral vascular injury and microcirculation dysfunction are involved in the pathogenesis of HSLE. The interrelation between apoptosis of oligodendrocytes and the microvascular damage are required to be studied in future investigations.

Increased expression of CD55 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.

PURPOSE: To analyze the expression of complement delay-accelerating factor (CD55) in nasopharyngeal carcinoma and its correlation with clinicopathologic features, including survival rate. METHODS: Eighty-two nasopharyngeal carcinoma tissues were evaluated for CD55 expression using immunohistochemistry. The association between CD55 expression and various clinicopathological characteristics including overall survival was analyzed. RESULTS: Immunohistochemical analysis revealed that the protein expression of CD55 detected in nasopharyngeal carcinoma tissues was higher than that in the normal nasopharyngeal tissue (P=0.003). In addition, high levels of CD55 protein were positively correlated with the status of lymph node metastasis (P=0.02) and distant metastasis (P=0.01), and clinical stage (P=0.002) of nasopharyngeal carcinoma patients. Patients with positive CD55 expression had a significantly shorter overall survival time than did patients with negative CD55 expression (P=0.001). Multivariate analysis suggested that the expression pattern of CD55 protein was an independent prognostic indicator (P=0.009) for the survival of patients with nasopharyngeal carcinoma. CONCLUSION: The data from this study suggest, for the first time, that CD55 is frequently expressed in nasopharyngeal carcinoma and its expression is associated with decreased patient survival; therefore, CD55 expression may be a potential unfavorable prognostic factor for patients with nasopharyngeal carcinoma.

[Effect of Tongxinluo on nestin and vascular endothehal growth factor mRNA expression in rat brain tissue after cerebral ischemia-reperfusion injury].

OBJECTIVE: To investigate the expressions of nestin and vascular endothehal growth factor (VEGF) mRNAs in rat brain tissue after cerebral ischemia-reperfusion injury and their changes in response to Tongxinluo (a traditional Chinese herbal preparation) treatment. METHODS: Cerebral ischemia was induced in rats by temporary middle cerebral artery occlusion (MCAO) followed by treatment with Tongxinluo at high and low doses. On days 3, 7, 14 and 21 after MCAO, nestin and VEGF mRNA expressions in the ependyma, subventricular zone (SVZ), and hippocampal subdentate gyrus zone (HDG) in the ischemic hemisphere were quantitatively analyzed using immunohistochemistry and RT-PCR. RESULTS: Compared with the sham-operated group, the rats with cerebral ischemia-reperfusion injury showed significantly increased nestin-positive neurons and VEGF mRNA expression in the SVZ and HDG 7, 14 and 21 days after MCAO (P<0.05). Treatment with Tongxinluo, especially at high doses, significantly increased the number of nestin-positive neurons and VEGF mRNA expression in the rats 7, 14 and 21 days after MCAO (P<0.05). CONCLUSION: Focal cerebral ischemia in rats results in rapid response and proliferation of neural stem cells in the SVZ and HDG in the ischemic hemisphere possibly by increasing VEGF mRNA expression in the adjacent tissues around the ischemic focus. Tongxinluo may enhance the differentiation and proliferation capacity of the neural stem cells after MCAO by inducing the expression of VEGF mRNA.

[Roles of bcl-2/bax expression and oligodendrocyte apoptosis in the pathogenesis of heroin-induced spongiform leucoencephalopathy].

OBJECTIVE: To investigate the role of oligodendrocyte apoptosis under the regulation of the bcl-2/bax protein expression in brain white matter in the pathogenesis of heroin-induced spongiform leucoencephalopathy (HSLE). METHODS: Samples of frontal lobe, cerebellum, and corpus callosum were obtained from the brains during autopsy of 4 HSLE cases and 5 normal controls and underwent light microscopy and electron microscopy. Immunocytochemistry was used to detect the expression of myelin basic protein (MBP), caspase-3, bcl-2 protein, and bax protein. RESULTS: Widespread demyelination was seen in the white matter of the frontal lobe, cerebellum and corpus callosum of the HSLE cases, most severely in the cerebellum. The levels of caspase-3 and bax expression of the HSLE group were significantly higher than those of the control group (both P <0.05) , however, the bcl-2 level of the HSLE group was no significantly different from that of the control group (P > 0.05). CONCLUSION: Widespread demyelination in the white matter is a prevailed pathological change of HSLE. Oligodendrocyte apoptosis under induced by the decrease of bcl-2/bax ratio may contribute to the pathogenesis.