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Background: Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion. Methods: A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed. Results: There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256). Conclusions: Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

Background Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion. Methods A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed. Results There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P=0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P=0.256). Conclusions Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

Purpose: We aimed to explore whether exposure to the Chinese famine in early life was associated with hyperuricemia in adulthood. Methods and Results: Two population-based cross-sectional surveys involving randomly selected Chinese adults aged 35–74 years were conducted in Qingdao, China in 2006 and 2009. 9055 subjects from the two surveys were grouped into four birth groups of fetal/infant exposed(born between 1959/1/1 and 1962/12/31), childhood exposed(born between 1950/1/1 and 1958/12/31), adolescence exposed(born between 1942/1/1 and 1949/12/31) and the unexposed(born before 1941 and after 1963). Multivariate logistic regression models were used to calculate the odd ratios (ORs) and 95% confidence intervals (CIs) of hyperuricemia in different exposed groups. Overall, famine exposure in the fetal/infant period, childhood and adolescence was not associated with adulthood hyperuricemia (all P>0.05). In females, childhood exposed group(OR=1.59, 95%CI:1.25-2.02) and adolescence exposed group(OR=1.74, 95%CI:1.30-2.33) both had higher risks to have hyperuricemia in adult. However, this difference was not found in fetal/infant exposed group. In males, no significant relation was observed in any famine exposed group (all P>0.05). Conclusions: Exposure to famine in childhood and adolescence is associated with an increased risk of hyperuricemia for adulthood of females, but not in males. Adequate nutrition during early life appears to be beneficial to prevent hyperuricemia of adult females.

Background and Aims Chronic inflammation and renin-angiotensin system (RAS) overactivation have been demonstrated as a central mechanism that results in the development of progressive chronic kidney disease (CKD). Evidences have indicated that tertiary lymphoid tissues (TLT) form after acute kidney injury (AKI), especially in old-aged mice. Heterogeneous fibroblasts which appear and secret proinflammatory cytokines after AKI underlie TLT formation. There is an association between TLT sizes and impaired renal function along with increase of proinflammatory cytokines, suggesting a probable cause of persistent inflammation after AKI. In this study, we explored the relationship between TLT development and RAS activity. The phenotypes of heterogeneous fibroblasts diversified after AKI is also investigated. Method Here we utilized ischemia-reperfusion injury to cause ensuing CKD both in a CD-1 and C57BL6J mice model. We also used staining of CD3 and B220 to label and confirm multiple TLTs which represents T and B lymphocytes respectively. Results Administration of losartan, a kind of RAS inhibitor, offered protection against subsequent CKD development and attenuated number and size of TLT besides blood pressure reduction. Moreover, heterogeneous fibroblasts diminished and proinflammatory cytokines such as CXCL13, CCL21 and CCL19 which trigger the initiation of TLT were downregulated. In experiments of several fibroblast cell lines, angiotensin II (Ang II) administration could induce differentiation of fibroblasts with distinct phenotypes expressing p75 neurotrophin receptor and retinaldehyde dehydrogenase 2 which contribute to TLT formation. These fibroblasts expressing PDGFRβ stimulated production of aforementioned proinflammatory cytokines and expression of pro-fibrotic genes. Conclusion Our data demonstrates that TLT plays an important role in AKI-CKD transition. We also verify that Ang II causes phenotypic change of fibroblasts which constitute TLT. Losartan can ameliorate TLT formation through inhibition of these distinctive fibroblasts. It is a plausible mechanism to reduce ensuing CKD.

Background and Aims Pericytes are mesenchyme-derived perivascular cells attached to the abluminal surface of capillaries as well as the major origin of myofibroblasts in the animal model of unilateral ureteral obstruction (UUO) and ischemia-reperfusion injury (IRI). Although previous studies reported that myofibroblasts may be beneficial during acute kidney injury (AKI) via growth factor secretion, reconstitution and stabilization of the collagen framework for tubular cell regeneration, lack of solid evidence and definite mechanism make the role of pericyte/myofibroblast in AKI remain controversial. Method To clarify this, we used platelet-derived growth factor receptor β (PDGFRβ)-specific antibody following AKI in C57BL/6 mice to inhibit pericytes. In the meantime, We used Gli1-CreERT2;Cxcl12fl/fl genetically modified mice to conditionally knockout CXCL12 specifically in pericytes before IRI. Results The expression of PDGFRβ on pericytes increased after IRI. In group of administration of PDGFRβ antibody, proliferation and transition to myofibroblasts of pericytes were inhibited. Inflammation became worse and renal recovery was impeded after AKI. The chemokine stromal cell-derived factor-1 (SDF-1) which is also known as the C-X-C-type chemokine CXCL12 decreased as well. Furthermore, we demonstrated that CXCL12 was secreted mainly by pericytes and its receptor CXCR4 was expressed on tubular cell during IRI by in situ hybridization. When knockout of CXCL12 was performed before IRI, the renal microvascular rarefaction was noted after AKI and the recovery of renal function was impaired. Renal tubular cell proliferation decreased and apoptosis increased as well. Conclusion In summary, these findings demonstrated that pericytes contribute to renal repair after IRI through CXCL12 secretion.

Background Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion.Methods A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed.Results There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P=0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P=0.256).Conclusions Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

Background and Aims Pericyte-myofibroblast transition is activated after acute kidney injury (AKI) and is the major mechanism of ensuing chronic kidney disease (CKD). Nevertheless, the role of pericyte in renal regeneration after AKI has not been deeply investigated. Many studies have shown that pericyte can secret growth factors such as fibroblast growth factor 1 and 7 (FGF-1, FGF-7) and is essential for structure support and vascular integrity in normal kidney. We supposed that the ablation or inhibition of pericytes during AKI would retard renal repair. Method Our study demonstrated that activated pericytes/myofibroblast was beneficial for renal regeneration after AKI. We here performed pericyte ablation and pericyte inhibition after ischemia-reperfusion renal injury by using transgenic mice such as Gli1-CreERT2;iDTR mice and blockade of platelet-derived growth factor receptor β (PDGFRβ), respectively. Results Renal injury was more severe and renal recovery was worse in groups of pericyte ablation or inhibition compared to control groups. Ki67 positive tubular cells which indicated renal regeneration were much more in control groups than that in groups of pericyte ablation or inhibition. We also found higher macrophage number as well as higher inflammatory factor including tumor necrosis factor-α and interleukin-1β which indicated more severe inflammation in groups of pericyte ablation or inhibition. Conclusion These studies suggest that pericytes play a beneficial role during renal recovery after AKI. These findings delineate the adequate timing when we target on pericyte/myofibroblast to ameliorate renal fibrosis and avoid to impede renal regeneration at the same time. Further research is still needed to clarify the change of specific gene and signalling pathway after pericyte ablation or inhibition. These are promising findings that provide opportunities to develop new targets to promote AKI recovery and to ameliorate renal fibrosis.