Comparative Efficacy of Subthreshold Micropulse Laser Photocoagulation versus Conventional Laser Photocoagulation for Diabetic Macular Edema: A Meta-Analysis.

BACKGROUND: Laser photocoagulation is an effective procedure for the treatment of diabetic macular edema (DME). However, the beneficial effects of conventional laser photocoagulation (CLP) are accompanied by the destruction of retinal photoreceptors. Therefore, subthreshold micropulse laser photocoagulation (SMLP) was proposed for DME. OBJECTIVES: This meta-analysis study was performed to evaluate the efficacy and safety of SMLP compared with CLP for the management of DME. METHODS: The PubMed, Embase, Web of Science, Cochrane, SinoMed, ClinicalTrials.gov, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, published until Dec 2021, were searched to identify studies evaluating the clinical outcomes of SMLP for DME. RESULTS: Eight randomized controlled trials were selected for this meta-analysis involving a total of 546 eyes (275 eyes in SMLP group and 271 eyes in CLP group). SMLP of different wavelengths (577 nm and 810 nm) and duty cycles (5% and 15%) was applied. The pooled outcomes showed that SMLP group, especially 577 nm and 810 nm 15% duty cycle parameter settings, had a statistically significant higher efficacy than CLP group in terms of BCVA (MD = -0.02, 95% CI: -0.03 to -0.01, p < 0.01; MD = -0.09, 95% CI: -0.09 to -0.09, p < 0.01) and showed more significant advantages than CLP group in resolving macular edema assessed by reduction of CMT (MD = -32.87, 95% CI: -37.61 to -28.13, p < 0.01; MD = -8.01, 95% CI: -9.06 to -6.96, p < 0.01), whereas the efficacy of 577 nm and 810 nm 5% duty cycle SMLP subgroups remained numerically superior to CLP group, but nonsignificantly (p > 0.05). In the field of CS, SMLP group (no matter parameter settings) resulted in better preservation of CS compared to CLP group (MD = 1.96, 95% CI: 1.47-2.46, p < 0.01). CONCLUSIONS: Compared with CLP, SMLP may get superior efficacy and safety on improvement of BCVA, reduction of CMT, and preservation of CS. In clinical, SMLP can be considered as a safe and effective therapy in the management of DME.

Suppression of liver transplant rejection by anti-donor MHC antibodies via depletion of donor immunogenic dendritic cells.

BACKGROUND: We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, a tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC (MHCI) antigen (DST-antibodies). METHODS: We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively. RESULTS: Preoperative transfer of DST-antibodies or DST pretreatment eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a+CD11b/c+ immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8+ T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the proliferative response of recipient regulatory T cells, DST-primed sera and the anti-donor MHCII antibody did not. CONCLUSION: DST-antibodies and anti-donor MHCII antibodies could suppress the CD8+ T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathways of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII- graft cells and recipient cells.

MicroRNA-936/ERBB4/Akt axis exhibits anticancer properties of gastric cancer through inhibition of cell proliferation, migration, and invasion.

Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.

[Effects of PGPR inoculation on photosynthesis and physiological-ecological characteristics of apple seedlings under drought stress]. / å¹²æ—±ä¸‹æŽ¥ç§æ ¹é™ ä¿ƒç”Ÿç»†èŒå¯¹è‹¹æžœå®žç”Ÿè‹—å ‰åˆå’Œç”Ÿç†ç”Ÿæ€ç‰¹æ€§çš„å½±å“.

The effects of inoculation of rhizosphere-promoting bacteria (PGPR) on photosynthesis and physiological-ecological characteristics of apple tree seedlings under drought conditions were investigated in this study, aiming to provide a theoretical basis for the application of PGPR in plant drought resistance. In the pot experiment, the rhizosphere-promoting bacterium YX2 which had both ACC deaminase activity and strong phosphorus solubilizing ability was selected as the tested strain. Apple seedlings were grown under four different irrigation levels i.e., control (CK), mild drought (LD), moderate drought (MD), and severe drought (SD) with soil moisture equivalent to 70%-80%, 55%-65%, 40%-50% and 25%-35% of field water holding capacity, respectively. Inoculation of PGPR alleviated the damaging effects of drought on growth by improving relative water content and chlorophyll content in apple tree seedlings. In addition, PGPR inoculated individuals exhibited higher antioxidant enzyme activity, chlorophyll fluorescence values, stomatal conductance and photosynthetic rate and lower relative conductivity and lipid peroxidation. Our results suggested that PGPR-YX2 alleviated the negative effects of drought stress on the growth and net photosynthetic rate by improving the antioxidant system, water content and membrane functioning.

Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer's patches.

Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1+ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection.

Direct evidence for activated CD8+ T cell transmigration across portal vein endothelial cells in liver graft rejection.

BACKGROUND: Lymphocyte recruitment into the portal tract is crucial not only for homeostatic immune surveillance but also for many liver diseases. However, the exact route of entry for lymphocytes into portal tract is still obscure. We investigated this question using a rat hepatic allograft rejection model. METHODS: A migration route was analyzed by immunohistological methods including a recently developed scanning electron microscopy method. Transmigration-associated molecules such as selectins, integrins, and chemokines and their receptors expressed by hepatic vessels and recruited T-cells were analyzed by immunohistochemistry and flow cytometry. RESULTS: The immunoelectron microscopic analysis clearly showed CD8ß(+) cells passing through the portal vein (PV) endothelia. Furthermore, the migrating pathway seemed to pass through the endothelial cell body. Local vascular cell adhesion molecule-1 (VCAM-1) expression was induced in PV endothelial cells from day 2 after liver transplantation. Although intercellular adhesion molecule-1 (ICAM-1) expression was also upregulated, it was restricted to sinusoidal endothelia. Recipient T-cells in the graft perfusate were CD25(+)CD44(+)ICAM-1(+)CXCR3(+)CCR5(-) and upregulated α4ß1 or αLß2 integrins. Immunohistochemistry showed the expression of CXCL10 in donor MHCII(high) cells in the portal tract as well as endothelial walls of PV. CONCLUSIONS: We show for the first time direct evidence of T-cell transmigration across PV endothelial cells during hepatic allograft rejection. Interactions between VCAM-1 on endothelia and α4ß1 integrin on recipient effector T-cells putatively play critical roles in adhesion and transmigration through endothelia. A chemokine axis of CXCL10 and CXCR3 also may be involved.

Long non-coding RNAs: new players in ocular neovascularization.

Pathological neovascularization are the most prevalent causes of moderate or severe vision loss. Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in numerous biological processes and complicated diseases. However, the role of lncRNAs in ocular neovascularization is still unclear. Here, we constructed a murine model of ocular neovascularization, and determined lncRNA expression profiles using microarray analysis. We identified 326 or 51 lncRNAs that were significantly either up-regulated or down-regulated in the vaso-obliteration or neovascularization phase, respectively. Based on Pearson correlation analysis, lncRNAs/mRNAs co-expression networks were constructed. GO enrichment analysis of lncRNAs-co-expressed mRNAs indicated that the biological modules were correlated with chromosome organization, extracellular region and guanylate cyclase activator activity in the vaso-obliteration phase, and correlated with cell proliferation, extracellular region and guanylate cyclase regulator activity in the neovascularization phase. KEGG pathway analysis indicated that MAPK signaling was the most significantly enriched pathway in both phases. Importantly, Vax2os1 and Vax2os2 were not only dynamically expressed in the vaso-obliteration and neovascularization phases, but also significantly altered in the aqueous humor of patients with neovascular age-related macular degeneration (AMD), suggesting a potential role of lncRNAs in the regulation of ocular neovascularization. Taken together, this study provided novel insights into the molecular pathogenesis of ocular neovascularization. The intervention of dysregulated lncRNA could become a potential target for the prevention and treatment of ocular vascular diseases.

Trafficking of recirculating lymphocytes in the rat liver: rapid transmigration into the portal area and then to the hepatic lymph.

BACKGROUND: We have investigated how recirculating lymphocytes patrol the liver in a normal steady state. METHODS: Thoracic duct lymphocytes of congeneic rats were intravenously transferred to host rats and donor cell trafficking in the liver and hepatic lymph was examined. Host hepatic lymph nodes (HLNs) were selectively removed, which allowed liver-derived donor cells to collect in the thoracic duct without transit in the intervening HLNs. RESULTS: The number of donor cells in the thoracic duct lymph significantly increased over the baseline 3, 5 and 11 h after transfer in the HLN-removed, non-pretreated, and HLN-ligated (in which a lymph efflux was blocked) groups, respectively. Histologically, donor cells appeared in the portal area from 0.5 h after transfer and frequently attached to the basal lamina of portal vein both externally and internally. Three hours after transfer, a few donor cells appeared in the subcapsular sinus of HLNs. CONCLUSION: The minimal transit time of rat recirculating lymphocytes is 3-4 h in the liver and 5-8 h in the hepatic LNs, in a normal steady state. Recirculating lymphocytes might transmigrate through the portal vein as well as the sinusoid in the periportal zone. This rapid transit might enable an efficient surveillance of the liver portal area by the recirculating lymphocytes.

Predominant donor CD103+CD8+ T cell infiltration into the gut epithelium during acute GvHD: a role of gut lymph nodes.

The existence of donor effector cell subsets responsible for either gut or skin graft-versus-host disease (GvHD) is still undetermined. We examined the trafficking and role of donor CD8(+) intra-epithelial lymphocytes (IELs) in the gut and skin epithelia concerning alpha E beta 7 integrin (CD103) expression, using a rat acute lethal GvHD model. Most CD103(+) donor cells were CD8(+) and showed a proliferative activity in the target epithelia. On the other hand, activated donor T cells in the host lymphoid tissues did not express CD103, indicating the presence of CD8(+) IEL precursors in the lymphoid tissues that may up-regulate CD103 only after migrating to the target organs. At the late stage of GvHD, while >80% of the donor CD8(+) IELs were CD103(+) in the gut epithelium, both CD4(+) and CD103(+)CD8(+) T cells evenly accumulated in the skin epidermis. The CD103 expression by donor CD8(+) IELs especially in the gut was also correlated with the clinical GvHD manifestations. Furthermore, the selective removal of gut lymph nodes (LNs) but not skin LNs suppressed the infiltration of CD103(+) donor IELs in the gut and alleviated intestinal GvHD. In conclusion, CD103(+)CD8(+) donor T cells predominantly infiltrate into the gut epithelium and are responsible for the manifestations of intestinal GvHD. This pathology is at least partly dependent on the gut LNs.

Systemic transmigration of allosensitizing donor dendritic cells to host secondary lymphoid organs after rat liver transplantation.

UNLABELLED: Donor dendritic cell (DC) migration and allosensitization in host secondary lymphoid organs after liver transplantation are ill defined. We used rat models to investigate graft-derived cells and intrahost allosensitization. Liver transplantation induced diffuse blood-borne migration of donor major histocompatibility class II antigen-positive (MHCII(+)) cells and MHCI(+) cells from the graft to host secondary lymphoid organs, not only the spleen, but also lymph nodes and Peyer's patches. The migrated MHCII(+) cells included DCs and some T cells and B cells. The DCs formed clusters with host BrdU(+) cells where they up-regulated CD86(+), and a CD8(+) T cell proliferative response originated within 24 hours after liver transplantation, demonstrating that these DCs can quickly mature and trigger direct allosensitization in host lymphoid organs. Transfer of allogeneic bone marrow cells also induced DC transmigration and a similar host response. In contrast, allogeneic thoracic duct lymph cells contained many fewer transmigrating DCs, and their transfer induced a comparable T cell response but significantly weaker CD8(+) T cell proliferation. Thus, there is a different outcome via the indirect pathway by host DCs that have captured donor alloantigens. CONCLUSION: The rat liver as well as bone marrow contains an immature DC population that can systemically transmigrate through blood vessel walls of the host secondary lymphoid organs, quickly mature, and induce diffuse intrahost CD8(+) T cell responses, which may promote graft rejection.

[Histopathological study of the effect of preservative-free 1% lidocaine on rabbit lens epithelial cells].

OBJECTIVE: To assess whether preservative-free 1% lidocaine is capable of loosing the junction between the rabbit lens epithelial cells (LECs) and between the cells and capsules and is capable of destroying the LECs, in order to provide scientific basis for pursuing safe and effective drugs to eliminate LECs in cataract surgery and to prevent capsular pacification. METHODS: Lens capsule specimens were collected from 29 rabbits (58 eyes) and divided into 3 groups: balanced salt solution (BSS) group (exposed to BSS for 1 minute), lidocaine group (exposed to preservative-free 1% lidocaine for 1 minute) and the control group. Specimens were stained with trypan blue and alizarin red. Photomicrographs of each capsule were taken to observe the viability of LECs and count the number of dead LECs. The histopathologic changes of LECs treated with lidocaine were evaluated by histological method and transmission electron microscope. RESULTS: The rate of dead LECs of the anterior and the equatorial lens capsules in control group was (1.51 +/- 0.39)%, and (1.52 +/- 0.32)%, respectively. The rate of dead LECs of the anterior and the equatorial lens capsules irrigated with BSS was (1.78 +/- 0.50)% and (1.77 +/- 0.47)%. The rate of dead LECs of the anterior and the equatorial lens capsules irrigated with preservative-free 1% lidocaine was (13.01 +/- 4.67)% and (9.59 +/- 3.35)%, respectively. The nested design ANOVA showed that the rate of dead LECs in the lidocaine group was greater than that in the control group or BSS group (P < 0.05), There was no significant difference in the number of dead cells between the anterior lens capsules and the equatorial lens capsules. After irrigated with lidocaine, cavities appeared ibetween the LECs and the capsule, cells detached from the capsule and showed vacuoles. The capsules of control group and BSS group showed a normal layer of LECs attached to the capsule. Under transmission electron microscope, in the lidocaine group, the junction between LECs and between the cell and the capsule were destroyed, many cells detached from the capsule and the rest arranged loosely. Some LECs dentes, and many vacuoles emerged, resulting in destruction of the cellular frame. CONCLUSION: Preservative-free 1% lidocaine may loose the junction between the LECs and between the cells and capsules, resulting in degeneration and death of the LECs.