Priming effects of nZVI on carbon sequestration and iron uptake are positively mediated by AM fungus in semiarid agricultural soils.

We investigated the priming effect of nanoscale zero-valent iron (nZVI) on carbon sink and iron uptake, and the possible mediation by AMF (arbuscular mycorrhizal fungi, Funneliformis mosseae) in semiarid agricultural soils. Maize seed dressings comprised of three nZVI concentrations of 0, 1, 2 g·kg-1 and was tested with and without AMF inoculation under high and low soil moistures, respectively. The ICP-OES observations indicated that both low dose of nZVI (1 g·kg-1) and high dose of nZVI (2 g·kg-1) significantly increased the iron concentrations in roots (L: 54.5-109.8 %; H: 119.1-245.4 %) and shoots (L: 40.8-78.9 %; H: 81.1-99.4 %). Importantly, the absorption and translocation rate of iron were substantially improved by AMF inoculation under the low-dose nZVI. Yet, the excess nanoparticles as a stress were efficiently relieved by rhizosphere hyphae, and the iron concentration in leaves and stems can maintain as high as about 300 mg·kg-1 while the iron translocation efficiency was reduced. Moreover, next-generation sequencing confirmed that appropriate amount of nZVI clearly improved the rhizosphere colonization of Funneliformis mosseae (p < 0.001) and the development of soil fungal community. Soil observations further showed that the hyphae development and GRSP (glomalin-related soil protein) secretion were significantly promoted (p < 0.05), with the increased R0.25 (< 0.25 mm) by 35.97-41.16 %. As a return, AMF and host plant turned to input more organic matter into soils for microbial growth and Fe uptake, and such interactions became more pronounced under drought stress. In contrast, high dose of nZVI (2 g·kg-1) tended to agglomerate on the surface of hyphae and spores, causing severe deformation and inactivation of AMF symbionts. Therefore, the priming effects of nZVI on carbon sequestration and Fe uptake in agricultural soils were positively mediated by AMF via the feedback loop of the plant-soil-microbe system for enhanced adaptation to global climate change.

High levels of TIMP1 are associated with increased extracellular matrix stiffness in isocitrate dehydrogenase 1-wild type gliomas.

Glioma progression is accompanied with increased tumor tissue stiffness, yet the underlying mechanisms are unclear. Herein, we employed atomic force microscopy analysis to show that tissue stiffness was higher in isocitrate dehydrogenase (IDH)-wild type gliomas than IDH-mutant gliomas. Bioinformatic analyses revealed that tissue inhibitor of metalloproteinase-1 (TIMP1) was one of the preferentially upregulated genes in IDH-wild type gliomas as compared to IDH-mutant gliomas, and its higher expression indicated worse prognosis of glioma patients. TIMP1 intensity determined by immunofluorescence staining on glioma tissues positively correlated with glioma tissue stiffness. Mechanistically, TIMP1 expression was positively correlated with the gene expression of two predominant extracellular matrix components, tenascin C and fibronectin, both of which were also highly expressed in IDH-wild type gliomas. By introducing IDH1-R132H-containing vectors into human IDH1-wild type glioma cells to obtain an IDH1-mutant cell line, we found that IDH1 mutation increased the TIMP1 promoter methylation through methylation-specific PCR. More importantly, IDH1-R132H mutation decreased both the expression of TIMP1, fibronectin, tenascin C, and the tumor tissue stiffness in IDH1-mutant glioma xenografts in contrast to IDH1-wild type counterparts. Moreover, TIMP1 knockdown in IDH-wild type glioma cells inhibited the expression of tenascin C and fibronectin, and decreased tissue stiffness in intracranial glioma xenografts. Conclusively, we revealed an IDH mutation status-mediated mechanism in regulating glioma tissue stiffness through modulating TIMP1 and downstream extracellular matrix components.

A map of the spatial distribution and tumour-associated macrophage states in glioblastoma and grade 4 IDH-mutant astrocytoma.

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.

Dicer deficiency impairs proliferation but potentiates anti-tumoral effect of macrophages in glioblastoma.

Glioblastoma is a lethal primary brain tumor with abundant immune-suppressive glioblastoma-associated macrophage (GAM) infiltration. Skewing immune suppressive GAMs towards an immune-activating phenotype represents a promising immunotherapeutic strategy against glioblastoma. Herein, we reported that genetic deletion of miRNA-processing enzyme Dicer in macrophages inhibited the growth of GL261 murine glioblastoma xenografts and prolonged survival of tumor-bearing mice. Single cell RNA sequencing (scRNA-seq) of the tumor-infiltrating immune cells revealed that Dicer deletion in macrophages reduced the proportion of cell-cycling GAM cluster and reprogramed the remaining GAMs towards a proinflammatory activation state (enhanced phagocytotic and IFN-producing signature). Dicer-deficient GAMs showed reduced level of cyclin-dependent kinases (CDK1 and CDK2) and increased expression of CDK inhibitor p27 Kip1, thus manifesting impaired proliferation. Dicer knockout enhanced phagocytotic activity of GAMs to eliminate GL261 tumor cells. Increased proinflammatory GAM clusters in macrophage Dicer-deficient mice actively interacted with tumor-infiltrating T cells and NK cells through TNF paracrine signaling to create a pro-inflammatory immune microenvironment for tumor cell elimination. Our work identifies the role of Dicer deletion in macrophages in generating an immune-activating microenvironment, which could be further developed as a potential immunotherapeutic strategy against glioblastoma.

PLXDC2 enhances invadopodium formation to promote invasion and metastasis of gastric cancer cells via interacting with PTP1B.

Plexin-domain containing 2 (PLXDC2) has been reported as an oncoprotein in several human malignancies. However, its expression and roles in gastric cancer remain largely unclear. In this study, we found that PLXDC2 was highly expressed in gastric cancer tissues, and the expression levels were positively correlated with clinicopathological features, but negatively with the patients' outcome. Cox regression analysis identified PLXDC2 as an independent prognostic indicator for the patients. Knockdown of PLXDC2 markedly suppressed the in vitro invasion and in vivo metastasis of gastric cancer cells, while overexpression of PLXDC2 resulted in opposite effects. Mechanistically, PLXDC2 enhanced the level of phosphorylated Cortactin (p-Cortactin) by physically interacting with protein tyrosine phosphatase 1B (PTP1B), an important dephosphorylase, to prevent its dephosphorylating of p-Cortactin, thereby promoting the formation of invadopodia. Collectively, our results indicate that PLXDC2 contributes to the invasion and metastasis of gastric cancer by inhibiting PTP1B to facilitate the invadopodium formation, and may serve as a potential prognostic biomarker and a therapeutic target for this disease.

Efficacy of intravitreal conbercept injection on short- and long-term macular edema in branch retinal vein occlusion.

AIM: To observe the best-corrected visual acuity (BCVA) and central foveal thickness (CFT) repeatedly after the intravitreal injection of conbercept (IVC) for treating cystoid macular edema (CME) in branch retinal vein occlusion (BRVO) and explore the relationship between the duration of CME and visual outcome. METHODS: Subgroup analysis was performed to compare short-term (within 90d of CME onset) and long-term (over 90d of CME onset) macular edema in BRVO. After an initial IVC, a pro re nata (PRN) strategy was performed according to the recurrence of CFT or decrease of BCVA. Analysis of variance using repeated measurements, statistical analysis following indicators including BCVA and CFT collected at baseline and 1, 3, and 6mo after IVC. RESULTS: Among the 60 cases included in this retrospective study, 36 were short-term CME, and 24 were long-term CME. There were statistical significances between and within groups of the BCVAs at different time points (P<0.001). The interaction was found between group and time (P=0.006), indicating the difference in the speed of BCVA improvement between groups. In particular, the improvement speed of BCVA in the short-term CME group was faster than that in the long-term CME group. There were significant differences between and with groups of the CFT at different time points (P<0.001). However, the interaction between group and time in relation to CFT had no significant differences (P=0.59). CONCLUSION: IVC treatment for CME following BRVO is effective and safe. The duration of CME before treatment is a significant predictor of the visual outcomes of patients with BRVO. The improvement of vision might be faster with early IVC treatment than with delayed treatment.

HOXA5 is amplified in glioblastoma stem cells and promotes tumor progression by transcriptionally activating PTPRZ1.

Although the tumorigenic potential of glioma stem cells (GSCs) is associated with multiple molecular alterations, the gene amplification status of GSCs has not been elucidated. Overexpression of HomeoboxA5 (HOXA5) is associated with increased glioma malignancy. In this study, we identify the gene amplification and protein overexpression of HOXA5 in GSCs and its function in regulating GSC maintenance and the downstream transcriptional effector, to explore the significance of HOXA5 amplification/overexpression for GSC identification and prognostic determination. The HOXA5 gene is significantly amplified in glioblastoma (GBM) and is an independent prognostic factor for predicting worse patient outcomes. Specifically, HOXA5 gene amplification and the resultant protein overexpression are correlated with increased proportions of GSCs and enhanced self-renewal/invasiveness of these cells. Disruption of HOXA5 expression impairs GSC survival and GBM tumor propagation. Mechanistically, HOXA5 directly binds to the promoter region of protein tyrosine phosphatase receptor type Z1 (PTPRZ1), thereby upregulating this gene for GSC maintenance. Suppression of PTPRZ1 largely compromises the pro-tumoral effect of HOXA5 on GSCs. In summary, HOXA5 amplification serves as a genetic biomarker for predicting worse GBM outcome, by enhancing PTPRZ1-mediated GSC survival.

Overexpression of carnitine palmitoyltransferase 1A promotes mitochondrial fusion and differentiation of glioblastoma stem cells.

Glioma stem cells (GSCs) are self-renewing tumor cells with multi-lineage differentiation potential and the capacity of construct glioblastoma (GBM) heterogenicity. Mitochondrial morphology is associated with the metabolic plasticity of GBM cells. Previous studies have revealed distinct mitochondrial morphologies and metabolic phenotypes between GSCs and non-stem tumor cells (NSTCs), whereas the molecules regulating mitochondrial dynamics in GBM cells are largely unknown. Herein, we report that carnitine palmitoyltransferase 1A (CPT1A) is preferentially expressed in NSTCs, and governs mitochondrial dynamics and GSC differentiation. Expressions of CPT1A and GSC marker CD133 were mutually exclusive in human GBMs. Overexpression of CPT1A inhibited GSC self-renewal but promoted mitochondrial fusion. In contrast, disruption of CPT1A in NSTCs promoted mitochondrial fission and reprogrammed NSTCs toward GSC feature. Mechanistically, CPT1A overexpression increased the phosphorylation of dynamin-related protein 1 at Ser-637 to promote mitochondrial fusion. In vivo, CPT1A overexpression decreased the percentage of GSCs, impaired GSC-derived xenograft growth and prolonged tumor-bearing mice survival. Our work identified CPT1A as a critical regulator of mitochondrial dynamics and GSC differentiation, indicating that CPT1A could be developed as a molecular target for GBM cell-differentiation strategy.

Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Contrast-enhanced ultrasound using SonoVue mixed with oral gastrointestinal contrast agent to evaluate esophageal hiatal hernia: Report of three cases and a literature review.

BACKGROUND: Due to a thicker abdominal wall in some patients, ultrasound artifacts from gastrointestinal gas and surrounding tissues can interfere with routine ultrasound examination, precluding its ability to display or clearly show the structure of a hernial sac (HS) and thereby diminishing diagnostic performance for esophageal hiatal hernia (EHH). Contrast-enhanced ultrasound (CEUS) imaging using an oral agent mixture allows for clear and intuitive identification of an EHH sac and dynamic observation of esophageal reflux. CASE SUMMARY: In this case series, we report three patients with clinically-suspected EHH, including two females and one male with an average age of 67.3 ± 16.4 years. CEUS was administered with an oral agent mixture (microbubble-based SonoVue and gastrointestinal contrast agent) and identified a direct sign of supradiaphragmatic HS (containing the hyperechoic agent) and indirect signs [e.g., widening of esophageal hiatus, hyperechoic mixture agent continuously or intermittently reflux flowing back and forth from the stomach into the supradiaphragmatic HS, and esophagus-gastric echo ring (i.e., the "EG" ring) seen above the diaphragm]. All three cases received a definitive diagnosis of EHH by esophageal manometry and gastroscopy. Two lesions resolved upon drug treatment and one required surgery. The recurrence rate in follow-up was 0%. The data from these cases suggest that the new non-invasive examination method may greatly improve the diagnosis of EHH. CONCLUSION: CEUS with the oral agent mixture can facilitate clear and intuitive identification of HS and dynamic observation of esophageal reflux.

External Validation of Two Predictive Models for Postoperative Fever After Retrograde Intrarenal Surgery in Pediatric Patients.

Objective: The aim of this study is to validate the efficacy and reliability of two predictive models for postoperative fever after retrograde intrarenal surgery (RIRS) in pediatric patients Materials and Methods: A total of 124 children who were treated with RIRS between August 2014 and August 2020 in our center were included. All the predictors were obtained by preoperative routine examinations. Receiver operative curve (ROC) and area under curve (AUC) were showed to compare the predictive power of the two models. Results: One hundred twenty-four children included of 94 boys and 30 girls, with median ages of 2.1 (1.3, 7.0) years and median body mass index of 17.3 (15.6, 20.6) kg/m2. The total points of the two nomograms were 81.0 (67.3, 90.3) and 45.5 (20.4, 94.0). Eventually, 21 children (16.9%) suffered from postoperative fever. With the exception of C-reactive protein values (25.0 mg/L vs 5.0 mg/L, p = 0.015), irrigation volumes (800 mL vs 500 mL, p = 0.01), and total points of the two predictive models (Nomogram 1: 88.0 vs 76.0, p < 0.001; Nomogram 2: 76.0 vs 39.0, p = 0.016), there was no statistical difference detected between the fever and nonfever groups. ROCs showed that Nomogram 1 presented with better predictive accuracy and efficacy with excellent AUC values of 0.805 in comparison with Nomogram 2 (0.805 vs 0.664, p = 0.025). Conclusion: We reported a sample of 124 children undergoing RIRS with a final stone-free rate of 87.1%. Twenty-one pediatric patients (16.9%) suffered from postoperative fever. Nomogram 1 presented with better predictive power for postoperative fever after RIRS in pediatric patients.

Comparison of efficacy and safety of minimally invasive procedures for 10-20 mm pediatric renal Stones-A bayesian network meta-analysis.

OBJECTIVE: To assess the efficacy and safety of various minimally invasive procedures for 10-20 mm pediatric renal stones by Bayesian network meta-analysis (NWA). METHODS: We searched clinical comparative trials published in Pubmed, Embase, Cochrane Library from inception to 12 April 2020. Two researchers evaluated the quality and extracted data individually. Data was analyzed using STATA and GEMYC R package. RESULTS: The overall network meta-analytic outcome of stone free rate (SFR) in a single session revealed that Retrograde Intrarenal Stone Surgery (RIRS), miniaturized percutaneous nephrolithotomy (mPCNL) and PCNL showed superiority to extracorporeal shockwave lithotripsy (ESWL). Statistical significance was not detected between any intervention from our pooled network analysis of complication rate. SMP was the most likely to ranking in first place to render stone free status, and it also showed the lowest risk possibility of complications. Mini-PCNL had longer operation time and hospitalization than ESWL. The global and loop inconsistency evaluation demonstrated a rather acceptable outcome apart from the comparisons of complication rate between two randomized control studies. DISCUSSION: Herein, the authors reviewed and explored the optimal management pattern for pediatric 10-20 mm renal stones. This NWA revealed RIRS and mPCNL could render higher SFR without increasing risk of complications compared with ESWL. Although SMP was deemed to be the best choice in our study, the limited source of study and sample size implied the results required to be further validated. In addition, there were still some problems requiring to be underlined for various surgical options. CONCLUSIONS: ESWL was inferior to RIRS, mPCNL and PCNL for 10-20 mm pediatric renal stones, among which SMP might be the most ideal option associated with the least possibility of complications and the highest probability of stone clearance.

Effect of Human Umbilical Cord Mesenchymal Stem Cells Transfected with HGF on TGF-ß1/Smad Signaling Pathway in Carbon Tetrachloride-Induced Liver Fibrosis Rats.

The research on human umbilical cord-derived mesenchymal stem cells (hUCMSCs) suggests promising therapeutic strategy for ameliorating liver fibrosis and it can be an effective alternative method of orthotopic liver transplantation. Hepatocyte growth factor (HGF) is the most basic cytokine involved in the inhibition of liver fibrosis and promotion of hepatocyte proliferation and regeneration. The objective of this study was to determine the possible mechanism about how the microencapsulated hUCMSCs made by alginate-poly-lysine-alginate (A-P-A) transfected with HGF could ameliorate liver fibrosis through the TGF-ß1/Smad signaling pathway. The microencapsulated cells were divided into four groups: hUCMSC (microcapsules of hUCMSCs), HGF (microcapsules of HGF+hUCMSCs), LV5-NC (microcapsules of LV5-NC, an rLV-EF1a-EGFP+Puro control lentiviral vector+hUCMSCs), and empty microcapsule (microcapsules without any hUCMSCs), and then transplanted by intraperitoneal injection into carbon tetrachloride (CCl4)-induced liver fibrosis rats, respectively. The results showed that the fibrosis in the hUCMSC, LV5-NC, and HGF groups was significantly alleviated. Moreover, the messenger RNA (mRNA) and protein levels of collagen I, collagen III, α-SMA, TGF-ß1, Smad2, and Smad3 were significantly decreased compared with the empty microcapsule group and these indices in HGF group were more decreased compared with hUCMSC and LV5-NC groups. This study indicated that microencapsulated hUCMSCs transfected with HGF could effectively improve CCl4-induced rat liver fibrosis and the possible mechanism was closely related to the inhibition of TGF-ß1/Smad signaling pathway.

Retinal vascular diameter changes assessed with a computer-assisted software after strabismus surgery.

AIM: To quantitatively investigate the retinal vascular diameter changes, analyzing the early and long-term effects on the retinal circulation, with 6-month follow-up. METHODS: Patients underwent horizontal strabismus surgery were enrolled prospectively. Retinal vessel diameters on color fundus photographs were assessed before and 1, 7d, 6mo after surgery, using a computer-assisted quantitative assessment software. To evaluate the retinal vascular caliber changes, retinal vascular diameters were calculated by means of the Parr-Hubbard formula as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). The arteriovenous ratio (AVR) was calculated as CRAE divided by CRVE. RESULTS: A total of 154 eyes of 104 consecutive patients were included. Compared with the data before surgery (121.55±24.67), the mean CRAE (131.18±28.29) significantly increased 1d after surgery (P=0.003), but went back to baseline level at 7d (118.89±30.35, P=0.15), and 6mo (123.22±15.32, P=0.60), so did the AVR (P<0.001, P=0.08, P=0.07). As for the mean CRVE, there was no significant difference between those four time points (172.43±33.25, 175.57±36.98, 174.03±40.18, 174.86±20.46, P=1.00). CONCLUSION: Strabismus surgery on both lateral and media rectus muscles, or single media rectus muscle may increase retinal blood flow during the early postoperative period, but would return to normal later. The number of transected anterior ciliary arteries rather might be the main cause of retinal hemodynamic changes early after strabismus surgery.

Stromal PD-1+ tumor-associated macrophages predict poor prognosis in lung adenocarcinoma.

Immunotherapies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) axis have been emerging as a promising therapeutic strategy to treat lung cancer. PD-1 is preferentially expressed by activated T lymphocytes; but whether/how its expression by tumor-associated macrophages (TAMs) in lung adenocarcinoma remains elusive. Herein, we investigate the frequency of PD-1 expression on TAMs in mouse allografts by flow cytometry analysis and evaluate the spatial distribution and clinicopathological significance of PD-1+ TAMs in 213 cases of human lung adenocarcinoma specimens by immunohistochemical staining. We find the expression of PD-1 by both mouse and human TAMs. Mouse PD-1+ TAMs possess unique transcriptional profile as compared to PD-1- TAMs. Furthermore, PD-1 is preferentially expressed by CD163+ TAMs in the tumor stroma than those in the tumor islets of lung adenocarcinoma. Stromal PD-1+ TAM infiltration is an independent predictor of reduced survival as determined by univariate (P < .001) and multivariate (P = .023) analysis. Moreover, patients with high stromal PD-1+ TAMs but low tumor cell PD-L1 expression have the shortest survival (P = .0001). Our study demonstrates that PD-1+ TAMs have unique gene expression characteristics and PD-1+ TAMs in the tumor stroma is a potential prognostic factor in lung adenocarcinoma, suggesting that a better understanding of PD-1+ TAMs will be beneficial for immunotherapy of lung adenocarcinoma patients.

Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms.

Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver; in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis; advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.

Retinal vessels caliber changes after strabismus surgery: results of 6mo follow-up.

AIM: To evaluate the effect of strabismus surgery on retinal vessels calibers with digital color fundus photographs. METHODS: Two hundred consecutive strabismus patients underwent surgery, and 118 patients (female/male, 55/63) who finished 6-month follow-up were finally included in this study. Optic disc-centered digital color fundus photographs of both eyes of all patients were taken prior to surgery and 6mo post surgery. The retinal vascular caliber of 116 operated eyes were measured using the computer program IVAN. The operated eyes were divided into 3 groups according to the surgical methods, recession of one muscle, one muscle recession and one muscle folding, one muscle resection and one muscle recession. The effect of number of altered muscles on retinal vessels was analyzed using statistic software SPSS 16.0. RESULTS: The mean age was 12.4±8.6y. Averaged central retinal artery equivalent (CRAE) of all patients was 120.31±23.02 µm preoperatively, and 122.87±15.93 µm six months after surgery. Averaged central retinal vein equivalent (CRVE) was 171.11±31.73 µm preoperatively and 175.02±21.00 µm postoperatively. There was no significant difference of averaged CRAE (P=0.22) or CRVE (P=0.19) before and after operation. Averaged arteriole to venule ratio (AVR) was 0.71±0.07 before surgery and 0.70±0.07 after surgery. Comparison of preoperative and postoperative retinal vessels calibers among different surgical groups did not show significant differences. Also, there was no advantage of rectus muscle folding to muscle resection. CONCLUSION: Up to 6mo after strabismus surgery, the retinal vascular calibers were not altered. No more than two muscles in one surgery are safe for retinal perfusion.

Risk Factors for Mesh Exposure after Transvaginal Mesh Surgery.

BACKGROUND: Mesh exposure after surgery continues to be a clinical challenge for urogynecological surgeons. The purpose of this study was to explore the risk factors for polypropylene (PP) mesh exposure after transvaginal mesh (TVM) surgery. METHODS: This study included 195 patients with advanced pelvic organ prolapse (POP), who underwent TVM from January 2004 to December 2012 at the First Affiliated Hospital of Chinese PLA General Hospital. Clinical data were evaluated including patient's demography, TVM type, concomitant procedures, operation time, blood loss, postoperative morbidity, and mesh exposure. Mesh exposure was identified through postoperative vaginal examination. Statistical analysis was performed to identify risk factors for mesh exposure. RESULTS: Two-hundred and nine transvaginal PP meshes were placed, including 194 in the anterior wall and 15 in the posterior wall. Concomitant tension-free vaginal tape was performed in 61 cases. The mean follow-up time was 35.1 ± 23.6 months. PP mesh exposure was identified in 32 cases (16.4%), with 31 in the anterior wall and 1 in the posterior wall. Significant difference was found in operating time and concomitant procedures between exposed and nonexposed groups (F = 7.443, P = 0.007; F = 4.307, P = 0.039, respectively). Binary logistic regression revealed that the number of concomitant procedures and operation time were risk factors for mesh exposure (P = 0.001, P = 0.043). CONCLUSION: Concomitant procedures and increased operating time increase the risk for postoperative mesh exposure in patients undergoing TVM surgery for POP.

Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain, which is characterized by the formation of extracellular amyloid plaques (or senile plaques) and intracellular neurofibrillary tangles. However, increasing evidences demonstrated that neuroinflammatory changes, including chronic microgliosis are key pathological components of AD. Microglia, the resident immune cells of the brain, is constantly survey the microenvironment under physiological conditions. In AD, deposition of ß-amyliod (Aß) peptide initiates a spectrum of cerebral neuroinflammation mediated by activating microglia. Activated microglia may play a potentially detrimental role by eliciting the expression of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) influencing the surrounding brain tissue. Emerging studies have demonstrated that up-regulation of pro-inflammatory cytokines play multiple roles in both neurodegeneration and neuroprotection. Understanding the pro-inflammatory cytokines signaling pathways involved in the regulation of AD is crucial to the development of strategies for therapy. This review will discuss the mechanisms and important role of pro-inflammatory cytokines in the pathogenesis of AD, and the ongoing drug targeting pro-inflammatory cytokine for therapeutic modulation.

[Long-term outcomes of the high vaginal uterosacral ligament suspension in treatment of the severe pelvic organ prolapse].

OBJECTIVE: To investigate the long-term objective and subjective outcomes of the transvaginal high uterosacral ligament suspension(HUS) in treatment of severe pelvic organ prolapse (POP) . METHODS: From Jun. 2003 to Mar.2013, 136 patients with severe POP quantitation (POP-Q) stage III-IV underwent transvaginal hysterectomy and HUS operation in the First Affiliated Hospital, General Hospital of People's Liberation Army. And 125 patients (91.9%, 125/136) were followed up at a mean of 5.4 years (range of 4.2-9.2 years) . Anterior colporrhaphy (79.2%, 99/125), posterior colporrhaphy (64.0%, 80/125), the perineorrhaphy (96.0%, 120/125) and tension-free suburethral slings (37.6%, 47/125) were performed concurrently, in which 53 (65%, 53/81) patients with severe cystocele and 5 patients (15%, 5/34) with rectocele were augmented with mesh, respectively. Concurrent operation and complications were studied. The objective success of the operation was defined as the leading vaginal edge above hymen.Subjective results were obtained quality-of-life questionnaires, including pelvic floor distress inventory short form (PFDI-20) and pelvic floor impact questionnaire short form (PFIQ-7). RESULT: The mean interval of following up was (5.4 ± 1.2) years.Four patients presented mild anterior vaginal wall prolapse, and the recurrence rate were 3.2% (4/125), but no reoperation and pessary treatment were needed. Therefore, the subjective and objective satisfaction rate was 94.4% (118/125) and 96.8% (121/125). The mean scores of PFDI-20 and PFIQ-7 at 5 years after the operations were 8, 7, significantly lower than 62, 64 (P < 0.01). There were 3 cases of ureter obstruction. Tension-free vaginal tape was performed on 47 cases with stress urinary incontinence (SUI) as indicated. The symptom of 2 patients was not improved significantly after the operation, but one was improved after 6 months. The rate of denovo SUI was in 2(1.6%, 2/125) patients, but no further treatment was needed. CONCLUSIONS: The transvaginal HUS was then conformed to be a safe, minimal traumatic, highly successful and durable procedure for severe POP, so it is worthy of being popularized for clinical application.