Dicyanopyridine derivatives: One-pot preparation, ACQ-to-AIE transformation, light-conversion quality and photostability.

Low cost and strong fluorescence emission are two important guarantees for luminogens used as light conversion agents. By one-pot multicomponent approach and inexpensive starting materials, three dicyanopyridine (DP) derivatives named as DCP (2-amino-6-methoxy-4-phenylpyridine-3,5-dicarbonitrile), DCO (2-amino-6-methoxy-4-(4-methoxyphenyl) pyridine-3,5-dicarbonitrile) and DCC (2-amino-4-(4-cyanophenyl)-6-methoxypyridine-3,5-dicarbonitrile) were designed and synthesized. Meanwhile, the ACQ-to-AIE transformation was successfully realized by altering substituent groups rather than traditional rotor-stator theory. Based on crystal analysis and theoretical calculations, the ACQ-to-AIE transformation is attributed to the tunable stacking modes and intermolecular weak interactions. Owing to matched fluorescence emission, low lost, high yield, and AIE activity, DCC is used as light conversion agents and doped in EVA matrix. The light conversion quality confirms that DCC can not only convert ultraviolet light, but also significantly improve the transmittance of 25 %/40 % EVA, whose photosynthetic photon flux density at 400-500 nm and 600-700 nm increased to 30.67 %/30.21 % and 25.37 %/37.82 % of the blank film, respectively. After 20 h of UV irradiation (365 nm, 40 W), the fluorescence intensities of DCC films can maintain 92 % of the initial values, indicating good photostability in the doping films. This work not only provides an excellent and low-cost light conversion agent, but also has important significance for ACQ-to-AIE transformation of luminogens.

METTL3 promotes osteogenic differentiation of human umbilical cord mesenchymal stem cells by up-regulating m6A modification of circCTTN.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) are promising seed cells in bone tissue engineering. circRNA and N6-methyladenosine (m6A) RNA methylation play important roles in osteogenic differentiation. Here, we investigated the potential relevance of a critical circRNA, hsa_circ_0003376 (circCTTN), and methyltransferase-like 3 (METTL3) in osteogenic differentiation of hUCMSCs. METHODS: Expression of circCTTN after hUCMSC osteogenic induction was detected by qRT-PCR. Three databases (RMBase v2.0, BERMP, and SRAMP) were used to predict m6A sites of circCTTN. RNA was enriched by methylated RNA immunoprecipitation (MeRIP), followed by quantitative real-time polymerase chain reaction to detect m6A level of circCTTN after METTL3 overexpression and osteogenic induction. RNA pull-down, Western blotting, and protein mass spectrometry were performed to investigate the potential mechanisms by which METTL3 promoted m6A modification of circCTTN. Bioinformatic analyses based on database (STRING) search and co-immunoprecipitation were used to analyze the proteins that interacted with METTL3. RESULTS: Overexpression of METTL3 promoted osteogenic differentiation of hUCMSCs and increased m6A level of circCTTN. Two potential m6A modification sites of circCTTN were predicted. No direct interaction between METTL3 and circCTTN was observed. Thirty-one proteins were pulled down by probes specific for circCTTN, including NOP2, and two m6A reading proteins, EIF3A and SND1. Bioinformatics analysis and co-immunoprecipitation showed that METTL3 interacted with EIF3A indirectly through NOP2. CONCLUSIONS: METTL3 promotes the osteogenic differentiation of hUCMSCs by increasing the m6A level of circCTTN. However, METTL3 does not bind directly to circCTTN. METTL3 interacts with circCTTN indirectly through NOP2 and EIF3A.

Population genomics of Agrotis segetum provide insights into the local adaptive evolution of agricultural pests.

BACKGROUND: The adaptive mechanisms of agricultural pests are the key to understanding the evolution of the pests and to developing new control strategies. However, there are few studies on the genetic basis of adaptations of agricultural pests. The turnip moth, Agrotis segetum (Lepidoptera: Noctuidae) is an important underground pest that affects a wide range of host plants and has a strong capacity to adapt to new environments. It is thus a good model for studying the adaptive evolution of pest species. RESULTS: We assembled a high-quality reference genome of A. segetum using PacBio reads. Then, we constructed a variation map of A. segetum by resequencing 98 individuals collected from six natural populations in China. The analysis of the population structure showed that all individuals were divided into four well-differentiated populations, corresponding to their geographical distribution. Selective sweep analysis and environmental association studies showed that candidate genes associated with local adaptation were functionally correlated with detoxification metabolism and glucose metabolism. CONCLUSIONS: Our study of A. segetum has provided insights into the genetic mechanisms of local adaptation and evolution; it has also produced genetic resources for developing new pest management strategies.

Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells.

AIM: To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation (LACC-HGT) primary cells cultured by high-grade transformation tissue and non-high-grade transformation (non-HGT) primary cells cultured by non-high-grade transformation tissue in proliferation, metastasis, drug susceptibility, and genes. METHODS: LACC-HGT primary cells were established by tissue block culture, and the 4th to 10th generation primary cells were selected as research objects. The cells were preliminarily identified by immunofluorescent staining. The differences between non-HGT and LACC-HGT primary cells in terms of proliferation, metastasis, and drug susceptibility were compared by cell counting kit-8 (CCK-8) assay, wound healing, and drug sensitivity experiments. Differentially expressed genes were screened using mRNA array. Gene expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: LACC-HGT primary cells were successfully cultured by tissue block culture. Immunofluorescence staining results showed that cytokeratin (CK) and CK7 expression levels were positive in LACC-HGT primary cells. CCK-8 results showed that the proliferation ability of LACC-HGT cells was significantly higher than that of non-HGT cells. Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells. LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells. Compared with non-HGT cells, 9566 differentially expressed genes were found in LACC-HGT primary cells, of which 5162 were up-regulated and 4404 were down-regulated. The expression of N-acetylneuraminate pyruvate lyase (NPL), MARVEL domain containing 3 (MARVELD3), syntabulin (SYBU), and allograft inflammatory factor 1 (AIF1) was higher in LACC-HGT cells than in non-HGT cells, whereas that of periostin (POSTN) was lower. CONCLUSION: LACC-HGT primary cells have faster proliferation, stronger migration ability, and poorer sensitivity to chemotherapy drugs than non-HGT primary cells. The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different. These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts.

Breaking the bottleneck of organic light conversion agents: Preparation, performance evaluation and intrinsic mechanism.

Poor photostability has become a major obstacle of organic fluorescent dyes (OFD) used as light conversion agent. To explore the intrinsic mechanisms of photodegradation and highly efficient means to enhance photostability, here, three s-triazine dyes and two 1,3,5-triphenylbenzene luminescent agents were designed and synthesized. Further, the relationships of photostability, intramolecular charge transfer effect, energy gap between singlet and triplet, and active oxygen generating capacity are analyzed and discussed. AIE activity, solid-state fluorescence emission, light conversion quality, and photostability combined with thermostability show TPT-DB (2,4,6-tris(4-(3,6-ditertbutyl-9H-carbazol-9-yl)phenyl)-1,3,5-triazine) is the best light conversion agent among of the dyes, whose photosynthetic photon flux density at 400-500 nm and 600-700 nm in doping film increased successively to 6.20% and 25.78% of the blank film, emission intensity can maintain 93.4% of the initial value after intensified UV radiation of 20 h (365 nm, 40 w), and has good thermal stability, Td up to 374 °C. Furthermore, oxygen-free environment was confirmed to be the most effective measure to enhance the photostability of OFD, thereby a simple and efficient method is adopted to block the diffusion of oxygen and significantly enhance the photostability of OFD by amphiphilic ethylene-vinyl alcohol copolymer. The work not only provides an excellent light conversion agent, but also clears the obstacles for the large-scale application of OFD as light conversion agents.

MiR-29a-3p inhibits high-grade transformation and epithelial-mesenchymal transition of lacrimal gland adenoid cystic carcinoma by targeting Quaking.

BACKGROUND: Lacrimal adenoid cystic carcinoma (LACC) is the most common orbital malignant epithelial neoplasm. LACC with high-grade transformation (LACC-HGT) has higher rates of recurrence, metastasis, and mortality than LACC without HGT. This study investigated the effects of microRNA-29a-3p (miR-29a-3p) in the pathogenesis of LACC-HGT. METHODS: An Agilent human miRNA microarray was used to screen the differentially expressed miRNAs (DEMs) in LACC and LACC-HGT tumor tissues. Then, the primary cells obtained in previous studies were used to determine the effect of miR-29a-3p. RESULTS: The expression of miR-29a-3p was abnormally lower in LACC-HGT than in LACC. miR-29a-3p can specifically target the 3' UTR of Quaking mRNA and down-regulate Quaking expression, thereby inhibiting the proliferation, migration, and epithelial-mesenchymal transition of LACC cells. CONCLUSIONS: This study illustrated that miR-29a-3p functions as a tumor suppressor by down-regulating the expression of Quaking to inhibit the tumorigenesis of LACC cells. This study may also reveal the pathogenesis of HGT in LACC cells and provide a reference for LACC-HGT targeted diagnosis.

Comparison of early osseointegration of non-thermal atmospheric plasma-functionalized/ SLActive titanium implant surfaces in beagle dogs.

Background: Hydrophilic dental implants are gaining increasing interest for their ability to accelerate bone formation. However, commercially available hydrophilic implants, such as SLActive™, have some major limitations due to their time-dependent biological aging and lower cost-effectiveness. The non-thermal atmospheric plasma (NTAP) treatment is a reliable way to gain a hydrophilic surface and enhance osseointegration. However, a few studies have been carried out to compare the osseointegration of NTAP-functionalized titanium implants and commercially available hydrophilic implants. Purpose: In this study, we compare the osseointegration abilities of the NTAP-functionalized titanium implant and Straumann SLActive. Material and methods: The NTAP effectiveness was examined using in vitro cell experiments. Then, six beagle dogs were included in the in vivo experiment. Straumann SLActive implants, SLA implants, and SLA implants treated with NTAP were implanted in the mandibular premolar area of dogs. After 2 w, 4 w, and 8 w, the animals were sacrificed and specimens were collected. Radiographic and histological analyses were used to measure osseointegration. Results: NTAP treatment accelerated the initial attachment and differentiation of MC3T3-E1 cells. In the in vivo experiment, bone parameters (e.g., BIC value and BV/TV) and volume of new bone of NTAP groups were close to those of the SLActive group. Additionally, although there was no statistical difference, the osseointegration of SLActive and NTAP groups was evidently superior to that of the SLA group. Conclusion: NTAP-functionalized implants enhanced cell interaction with material and subsequent bone formation. The osseointegration of the NTAP-functionalized implant was comparable to that of the SLActive implant at the early osseointegration stage.

Involvement of PI3K/Akt signaling pathway in promoting osteogenesis on titanium implant surfaces modified with novel non-thermal atmospheric plasma.

Non-thermal atmospheric plasma (NTAP) modification to induce a hydrophilic titanium (Ti) surface with less carbon contamination, has been demonstrated to boost the osteogenic responses. In this study, we investigated the underlying bone formation mechanism of NTAP-Ti, and the involvement of PI3K/Akt signaling pathway in regulating osteogenic activities on NTAP-Ti surfaces. NTAP was employed for Ti activation, and PI3K inhibitor, LY294002, was applied to the suppression of PI3K/Akt pathway. We systematically and quantitatively detected the cell morphology, attachment, proliferation, osteogenic differentiation and mineralization of MC3T3-E1 mouse preosteoblasts, and molecular expressions involved in osteogenesis and PI3K/Akt signaling pathway in vivo and in vitro. A descent in osteoblast proliferation on Ti surfaces in relation to LY294002. Alkaline phosphatase (ALP) activity, as well as matrix mineralization, was mitigated by PI3K inhibitor in NTAP-Ti. Likewise, the expression levels of osteogenesis-related genes [ALP, osteocalcin (Ocn), osteopontin (Opn) and runt-related transcription factor 2 (Runx2)] on NTAP-Ti were notably attenuated by LY294002, as confirmed by the results of osteogenesis-related proteins (ALP, and Runx2) expression analysis. In addition, the expression of PI3K/Akt signal pathway proteins further verified the inhibition of LY294002 on Ti surfaces modified by NTAP. Collectively, the PI3K/Akt signal pathway was involved in the amelioration of osteogenesis induced by NTAP modification. NTAP treatment for Ti activation is promising in augmented osteogenic potential through the activation of PI3K/Akt signal pathway.

Establishment of a human meibomian gland carcinoma cell model and analysis of differently expressed genes.

Meibomian gland carcinoma (MGC) is a malignant eyelid tumor with a high malignancy degree and poor prognosis. However, the lack of suitable cell and animal models has limited the study of MGC pathogenesis. In the present study, we established and identified one human MGC cell and one meibomian gland (MG) cell model by fresh surgical resection tissue block primary culture and differentially expressed gene assays. The outgrowth of MGC and MG cells was periodically observed after primary culture, and the first passage of MGC cells proceeded on the 14th day, whereas that for MG cells after three weeks. Cell ultrastructures were observed by transmission electron microscopy (TEM). Immunofluorescence staining showed that MGC and MG cells were both positive for cytokeratin (CK) and androgen receptor (AR). Orange granules were observed in the cytoplasm of MGC and MG cells using Oil red O staining, but they were stronger for MG cells than for MGC. CCK-8 detection demonstrated that the proliferation ability of MGC cells was stronger than that of MG cells. Moreover, during RNA sequence analyses, 3023 differential expressed genes were detected between MGC and MG cells. These genes were involved in biological processes such as cell division and positive regulation of cell migration; the signaling pathways mainly covered cell cycle and DNA replication. Further, the tumorigenic potential of MGC cells was examined by inoculating them subcutaneously into the right abdomen of three severely immunodeficient NOD -SCID mice. Transplanted tumors formed on day 11 after inoculation. The xenograft mouse tissues retained the same histological characteristics as the human MGC original tumor and MGC primary cells. Altogether, these results showed that the MGC and MG models were successfully cultured and established, and differentially expressed genes were successfully detected. We provided a useful model and molecular basis for studying the biological characteristics and pathogenesis of human MGC.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

MicroRNA-3907 promotes the proliferation and migration of sebaceous gland carcinoma of the eyelid by targeting thrombospondin 1.

MicroRNAs (miRNAs/miRs) play an important role in various types of carcinoma, including sebaceous gland carcinoma (SGC) of the eyelid. miR-3907 was found to be highly expressed in lung cancer; however, to the best of our knowledge, the biological role of miR-3907 in SGC has not previously been evaluated. The aim of the present study was to determine the role and mechanism of miR-3907 in the occurrence and development of SGC. miR-3907 was screened and identified as a novel upregulated miRNA in SGC tissues and cells, as determined using miRNA microarrays and reverse transcription-quantitative (RT-q) PCR analyses. Compared with the control group, cellular proliferation and migration were enhanced in the miR-3907 mimics group, and decreased in the miR-3907 inhibitor group. Moreover, miR-3907 negatively regulated thrombospondin 1 (THBS1) expression, as shown by bioinformatics prediction, RT-qPCR, western blotting and dual-luciferase reporter assays. In addition, compared with the control group, the small interfering (si) siRNA-THBS1 group exhibited enhanced proliferation and migration abilities, which were decreased in the THBS1 overexpression group. Furthermore, THBS1 overexpression was found to attenuate the stimulative effect of miR-3907 mimics, and THBS1-knockdown reversed the inhibitory effect of the miR-3907 inhibitor in SGC cells. Collectively, the results of the present study indicated that miR-3907 promoted the proliferation and migration of SGC by downregulating THBS1, and that this axis may be a potential target for the prognostic assessment and treatment of SGC.

Transcriptomic profiling and functional prediction reveal aberrant expression of circular RNAs during osteogenic differentiation in human umbilical cord mesenchymal stromal cells.

Circular RNAs (circRNAs) are crucial elements of non-coding RNA, that regulate various biological processes. To date, expression patterns and functional roles of circRNAs during osteogenic differentiation of human umbilical cord mesenchymal stromal cells (hUCMSCs) remain unknown. In this study, we analyzed RNA-sequence data to reveal expression profiles of circRNAs during osteogenesis of hUCMSCs, then elucidated the underlying mechanisms of action. We identified a total of 5457 circRNAs in hUCMSCs, of which 34 and 33 were upregulated and downregulated, respectively. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine functions and related pathways of differentially expressed circRNAs. Moreover, we applied bioinformatics tools to construct competing endogenous RNA networks, comprising 10 circRNAs, 46 micro RNAs and 413 mRNAs. Furthermore, we predicted protein-coding potential of the upregulated circRNAs then constructed a co-expression network comprising the top 5 upregulated circRNAs and 75 RNA-binding proteins. Next, we validated 6 differentially-expressed circRNAs and found that overexpressing circ-CTTN could promote osteogenesis of hUCMSCs. Overall, our findings indicate that clusters of circRNAs are aberrantly expressed in hUCMSCs during osteogenic differentiation, hence lay a foundation for future research into promoting hUCMSCs osteogenic differentiation and bone regeneration.

Bioinformatics identification of the candidate microRNAs and construction of a competing endogenous RNA regulatory network in lacrimal gland adenoid cystic carcinoma high-grade transformation.

Adenoid cystic carcinoma of the lacrimal gland (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in LACC high-grade transformation (LACC-HGT) compared with in LACC. The present study aimed to identify the candidate microRNAs (miRNAs/miRs) and construct a competing endogenous RNA (ceRNA) regulatory network for LACC-HGT. A miRNA microarray on paraffin-embedded tissues was performed to identify the differentially expressed miRNAs (DEMs) of LACC-HGT. The overlap with the salivary adenoid cystic carcinoma miRNA/RNA sequencing dataset in the Gene Expression Omnibus was used to identify candidate miRNAs. In order to construct a ceRNA regulatory network of LACC-HGT, a microarray of mRNA and circRNA in primary cell lines was performed. The circRNAs and genes with high expression in LACC-HGT were predicted as targeting miRNAs, and the circRNA-miRNA-mRNA regulatory network was constructed. miR-140-3p was identified as part of the ceRNA network and as a candidate miRNA, therefore this was further analyzed using reverse transcription-quantitative (RT-q)PCR. Overall, the Agilent Human microarray analysis identified a total of 16 DEMs from the LACC-HGT paraffin-embedded tissues. A total of 653 DECs and 9,566 DEGs of LACC-HGT primary cell lines were screened via the microarray of mRNA and circRNA. The ceRNA regulatory network was constructed using the cross-binding of circRNA-miRNA, miRNA-mRNA and the downregulated miRNAs in LACC-HGT to clearly demonstrate the circRNA-miRNA-mRNA interaction relationship. RT-qPCR results confirmed that miR-140-3p was downregulated in LACC-HGT tissues and primary cell lines compared with LACC. Target genes CD200 and parathyroid hormone-related protein were significantly upregulated in LACC-HGT primary cell lines. miR-140-3p and its target genes may play an important role in LACC-HGT pathogenesis. In conclusion, the current bioinformatics study constructed a ceRNA network based on a microarray, which may help identify novel miRNA therapeutic targets for LACC-HGT.

Postoperative severe visual impairment: surgical outcome of 165 patients with orbital tumours in the muscle cone.

OBJECTIVE: This study aimed to evaluate the risk factors of postoperative severe vision impairment (PSVI) for a primary orbital tumour in the muscle cone. METHODS: A retrospective analysis of the patients who underwent orbitotomy for primary intraconal tumours at the Tianjin Medical University Eye Hospital from January 2010 to December 2015. RESULTS: A total of 165 cases of orbitotomy for primary orbital tumours in the muscle cone were included in the study. Postoperatively, 12 cases with vision acuity ≤20/400 or ≥4 rows of vision decline and without any corrected effect were analysed as PSVI, including no light perception (NLP) for 3 cases. The multivariate logistic regression indicated that the tumour in orbital apex (P = 0.048, OR = 4.912, 95% CI: 1.011-23.866), severe optic nerve displacement (P = 0.030, OR = 6.007, 95% CI: 1.184-30.473) and intraoperative tight adhesion (P = 0.003, OR = 12.031, 95% CI: 2.282-63.441) were the independent risk factors for PSVI. CONCLUSIONS: The incidence of PSVI for the intraconal tumour was 7.3%, and the incidence of NLP was 1.8%. The tumour in orbital apex, severe optic nerve displacement and intraoperative tight adhesion were independent risk factors for PSVI.

Repetitive Transcranial Magnetic Stimulation on Motor Recovery for Patients With Stroke: A PRISMA Compliant Systematic Review and Meta-analysis.

OBJECTIVE: A systematic review and meta-analysis were conducted to determine the efficacy of repetitive transcranial magnetic stimulation in recovering motor function in patients with stroke. DESIGN: A comprehensive literature search was performed to identify studies published before September 20, 2018. Electronic databases were searched. Standard mean differences and 95% confidence intervals were used to evaluate the effects of repetitive transcranial magnetic stimulation. The stability and sensitivity of the results and sources of heterogeneity were also analyzed. The Cochrane Risk of Bias Tool was used to determine the quality of the studies. RESULT: Twenty randomized controlled trials (N = 841 patients) were included. The results showed that repetitive transcranial magnetic stimulation is beneficial to patients with poststroke hemiplegia, as demonstrated by the following four scales: the Fugl-Meyer Assessment (standard mean difference = 0.635, 95% confidence interval = 0.421 to 0.848); grip strength (standard mean difference = 1.147, 95% confidence interval = 0.761 to 1.534); Barthel Index (Standard mean difference = 0.580, 95% confidence interval = 0.377 to 0.783); and National Institutes of Health Stroke Scale (standard mean difference = -0.555, 95% confidence interval = -0.813 to -0.298). Few adverse events were observed. CONCLUSIONS: The analysis showed that low-frequency repetitive transcranial magnetic stimulation has a positive effect on grip strength and lower limb function as assessed by FMA.

Clinical outcome observation of the embolization of orbital vascular malformation with medical glue under direct intra-operative view.

BACKGROUND: Orbital vascular malformation often encircles normal tissue with ill-defined borders. It is easy to bleed during resection operation, making surgical treatment difficult and lesions hard to be removed completely. In this study we aimed to summarize the treatment outcomes by embolizing orbital vascular malformation with intraoperative intracavitary injection of medical glue . METHODS: A retrospective observational and cross-sectional case series study enrolled 31 patients (male = 9, female = 22) with orbital vascular malformations, who were treated from March 2008 to September 2017 at our institution. The clinical features, operation records, pathological reports and follow-up data were analyzed. RESULTS: The location of vascular malformations involved intraorbital (14 cases), superficial area of eyelid and/or face (7 cases), both intraorbital and superficial area (10 cases). Imaging examination showed a solitary mass with regular shape in 8 cases and a space occupying lesion with irregular shape and ill-defined margins in 23 cases. There were 9 cases had optic nerve involved. Surgical debulkling were performed via skin incision on the mass surface (5 cases), lateral orbitotomy (2 cases), and anterior orbitotomy (24 cases). During the operation, lesions were partly exposed and injected with medical glue. The amount of injected glue was 0.25 ml to 2.5 ml in divided doses. The lesions and remnant glue were removed after the glue had turned hard. The whole procedure caused less bleeding and was easier performing than usual. Topical skin aseptic inflammation took place on the same side of the superficial eyelid lesions in 3 cases. One patient suffered from sudden central retinal artery embolism on the third day post operation. With timely rescue and appropriate procedure, visual acuity recovered to 20/32. There were no recurrences in 29 cases. CONCLUSIONS: Embolization of orbital vascular malformation with medical glue intraoperatively made it easy to control hemorrhage. Surgeons should be careful with glue application methods in order to avoid complications.

Vasculogenic mimicry is a major feature and novel predictor of poor prognosis in patients with orbital rhabdomyosarcoma.

Vasculogenic mimicry (VM) is a key developmental program, frequently activated during cancer invasion and metastasis. The aim of the present study was to evaluate the role of VM in orbital rhabdomyosarcoma (RMS), the correlation between VM and tumor differentiation, recurrence and survival duration, as well as the contribution of epithelial cell kinase (EphA2) and matrix metalloproteinase-2 (MMP-2) in VM initiation. A total of 32 patients were enrolled to investigate the associations between VM in orbital RMS tumors and clinical characteristics, as well as its impact on overall survival. VM was identified and confirmed by CD31/periodic acid-Schiff double staining, while the presence of EphA2 and MMP-2 were examined by immunohistochemical analysis. VM was identified in eleven patients, particularly those with poorly differentiated orbital RMS (P=0.001). Patients with VM exhibited significantly worse survival rates (P=0.001, log-rank test), a significantly increased risk of mortality (P=0.008) and EphA2 and MMP-2 expression levels were enhanced (P=0.005 and 0.001, respectively). The VM and mitotic rate were independent predictors of poor prognosis (P=0.001 and 0.004, respectively), indicated by multivariate Cox proportional hazards models. These results demonstrated that VM is present in orbital RMS and represents an independent prognostic factor for overall survival. In addition, overexpression of EphA2 and MMP-2 may promote VM formation in orbital RMS.

[The cultivation and identification of lacrimal gland adenoid cystic cancer stem cells].

OBJECTIVE: To isolate and cultivate the Lacrimal gland Adenoid Cystic Carcinoma cells line, study Cancer Stem Cells properties. METHOD: Experimental study. Lacrimal gland adenoid cystic carcinoma cancer stem cells were cultivated in serum-free suspension culture and the morphological changes were observed. Cells were divided into two groups, the LACC-CSC experimental group and the LACC control group. The flow cytometry instrument was used to detect the expression of classical stem cell markers CD133 and ABCG2. Transwell chamber was used to detect the cancer stem cell aggressivity and differentiated into the vascular endothelial cells. The tumorigenic force in vitro xenotransplantation were applied. RESULT: LACC cells can grow suspensively after vaccinated in serum free medium and form tumor microspheres after 10-12 days. Flow cytometry experiments showed that the expression ratio of stem cell markers CD133 in LACC-CSC was (35.67 ± 6.86)%, significantly different to LACC with (0.46 ± 0.48)%, (t = 8.867, P < 0.05). Similarly, the expression ratio of stem cell marker ABCG2 in LACC-CSC was (39.99 ± 4.54)%, significantly different to LACC with (6.75 ± 1.34)%, (t = -9.932, P < 0.05). In vitro experiment of Matrigel invasion, LACC-CSC went through the matrigel basement membrane averagely (32.60 ± 8.79)/HP contrary to LACC with average (10.20 ± 2.77)/HP after 24 hours, showing statistically significance (t = 5.433, P < 0.05) between the two groups. After training for 48 hours, the difference between two groups was still obvious (t = 5.779, P < 0.05) with LACC-CSC average (62.60 ± 4.83)/HP to LACC (44.00 ± 5.34)/HP. When induced by serum medium containing VEGF and bFGF, LACC-CSC grew adherent gradually and cell morphological changes occurred after continuous induction to long spindle cells. When cultured into three-dimensional matrix structure they formed vessel samples and expressed vascular endothelial marker CD31 and CD34. Transplanted tumor in vitro experiment, mice of LACC-CSC group grew tumors in 9 days with 100% tumorigenic rate, whereas LACC group 12 days with 100% tumorigenic rate. CONCLUSIONS: LACC-CSC can be obtained through serum-free culture method. LACC-CSC grew suspensively and expressed classical stem cell markers. LACC-CSC were identified as cancer stem cells with stronger migration and invasion. LACC-CSC have tumorigenic force and multi-directional differentiation potential with general characteristics of the stem cell.

Establishment and characterization of a cell line from human adenoid cystic carcinoma of the lacrimal glands and a nude mouse transplantable model.

Using tissue block culture techniques, we established a new human tumor cell line derived from adenoid cystic carcinoma of the lacrimal glands (LACC-1). The LACC-1 cell line was successfully subcultured for more than 100 passages during the last two years. The outgrowth of cells was observed by day 5 after seeding, and then the cells were generated slowly. The first passage proceeded by day 32, and the classical epithelioid cell colonies formed by day 69 after inoculation. After eight passages, homogeneous epithelioid tumor cells appeared when we combined continuous passage, mechanical scraping, repeated adherence, and dissociation methods to remove the fibroblast cells. LACC-1 cells appeared as a histologically solid pattern and continuous passage culture. The population doubling time was approximately 37.1 h. LACC-1 cells appeared as an epithelioid monolayer culture on the cell culture flask and presented with a cobblestone-like appearance when they reached confluency. The nucleus was large and round with many abnormal mitoses. The nucleoplasm ratio was high. Multinucleated tumor giant cells appeared. LACC-1 cells showed a tendency to have overlapping growth without contact inhibition when the cell density continued to increase. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the LACC-1 cells were malignant tumor cells that were poorly differentiated. The surface of the LACC-1 cells exhibited affluent microvilli, protuberances and filopodia under SEM. The no. 84 generation LACC-1 cell line was inoculated subcutaneously into the subaxillary of nude mice and the tumorigenic potential was evident. The formation rate of the transplanted tumors was 100% at day 7 after inoculation. This finding showed that the LACC-1 cell line was malignant with tumorigenic ability. The xenograft tumors retained the same histological characteristics of a solid pattern as the LACC-1 original tumor after inoculation for 49 days. Under TEM observation, the xenograft tumor cells had the same ultrastructure as the LACC-1 cells. Immunohistochemical examination revealed the similarity of both cytoskeletal proteins (e.g., cytokeratin, vimentin, desmin and α-SMA) and S-100 expression in the original tumor, LACC-1 cells and xenograft tumors. Immunoreactivity of these proteins was gradually decreased in these three tissues. Reverse transcription-polymerase chain reaction demonstrated that the xenograft tumors originated from the human. Based on these results, the LACC-1 cell line provides a useful model for studying the biological characteristics of human ACC of the lacrimal glands.