[Treatment efficacy of dietary supplement Licofor for dry eye associated with meibomian gland dysfunction].

Objective: To evaluate the clinical efficacy of dietary supplement Licofor in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: This was a prospective, randomized controlled clinical trial. Sixty patients [25 males, 35 females, aged (42±13) years] who had dry eye associated with MGD were recruited in Xiangya Hospital of Central South University from December 2018 to October 2019. The patients were equally divided into two groups: 30 cases (60 eyes) in the experimental group and 30 cases (60 eyes) in the control group. All subjects were treated with eye hot compress, artificial tears and antibiotic ointment. After that, the experimental group and control group were received dietary supplementary Licofor or placebo daily for 12 weeks. The symptoms and signs of dry eye, morphology and function of meibomian gland, and inflammatory response were assessed at the beginning, 4th, 8th and 12th week of treatment. Results: After 12 weeks of treatment, statistically significant improvements in ocular surface disease index (OSDI) scores, tear break-up time (TBUT), corneal fluorescein staining (CFS), the morphology of eyelid margin, meibomian gland orifice, meibomian gland expressibility, meibum quality, and periglandular inflammatory cell density were determined in both groups (all P<0.05). In the Licofor group, the improvement of OSDI scores [16.7 (12.5, 20.8) vs 20.8 (18.8, 22.9), P<0.001], the morphology of eyelid margin, meibomian gland orifice and periglandular inflammatory cell density [443 (318, 513) vs 553 (415, 676)/mm2, P=0.002] were more significant (all P<0.05). Conclusion: The combined treatment of licofor and conventional treatment can significantly improve symptoms of dry eye, the morphology of eyelid margin, meibomian gland orifice, meibum quality, and eyelid inflammation response of dry eye associated with MGD.

Comparing critical speed modelling approaches and exploring relationships with match-play variables in elite male youth soccer players.

Background: A novel bi-exponential method has emerged to estimate critical speed (CS) and D-prime (D') from a 3-min all-out test (3MT). Objectives: To compare CS analysis methods to determine whether parameter estimations were interchangeable. Reference values and relationships with key soccer match-play variables were explored. Methods: Thirteen elite male youth (14-15 years old) players completed a 30 m shuttle run 3MT to estimate CS, D', rate of speed decline time constant, maximal speed (S max), time to S max (t max), and fatigue index (FI), using the traditional method and bi-exponential model on average (Bi-ExpAverage) and max speed settings (Bi-ExpMax-Speed). High-speed running (HSR) and sprinting distances and counts, and the number of accelerations were collected from two matches. Magnitude-based inferences (p < 0.05) with smallest worthwhile change of 0.2 effect sizes were used to analyse differences. Pearson's and Spearman's correlation coefficients were used to measure associations between CS model variables and match-play parameters. Results: There were significant differences between the traditional method and both bi-exponential models for CS and D', as well as between the bi-exponential models for all variables except t max. Using the Bi-ExpAverage model, strong correlations (r = 0.70-0.73; p < 0.05) were observed for D' and FI with the number of standardised and individualised HSRs, respectively. With the Bi-ExpMax-Speed model, there were strong correlations (r/ρ = 0.64-0.68; p < 0.05) between D' and the number of standardised HSRs and sprints, and the number of individualised sprints. Conclusion: There is a lack of interchangeability between analysis methods. It appears that D' and FI from the bi-exponential models could be associated with high-intensity actions in soccer match-play.

Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae.

To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography-mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.

Direct comparison of Neuroform and Enterprise stents in the treatment of wide-necked intracranial aneurysms.

AIM: To compare the complications and outcomes of Neuroform and Enterprise stents in the treatment of unruptured wide-necked aneurysms. MATERIALS AND METHODS: Under the auspices of the institutional review board, a review of a prospectively collected patient log identified 130 patients who underwent elective stent-assisted coil embolization of a wide-necked aneurysm, including 53 patients treated with an Enterprise stent and 77 patients treated with a Neuroform stent. Immediate and long-term clinical and radiographic outcomes were recorded for all patients. All patient data were handled in accordance with Health Insurance Portability and Accountability Act of 1996 (HIPAA) regulations. RESULTS: The technical success rate was 94%. Overall morbidity was 15% with Enterprise stents and 3% with Neuroform stents (p = 0.020). However, the type of stent used was not predictive of clinical outcomes as measured by the modified Rankin scale. In a multivariate analysis, the use of a Neuroform stent was one of the predictors of retreatment (p = 0.034). CONCLUSION: Multivariate analyses identified the use of Neuroform stents as an independent predictor of the need for retreatment and the use of Enterprise stents as an independent predictor of morbidity. However, the type of stent was not predictive of clinical outcome as measured by the modified Rankin scale.

Preoperative embolization of intracranial meningiomas: efficacy, technical considerations, and complications.

BACKGROUND AND PURPOSE: Preoperative embolization for intracranial meningiomas offers potential advantages for safer and more effective surgery. However, this treatment strategy has not been examined in a large comparative series. The purpose of this study was to review our experience using preoperative embolization to understand the efficacy, technical considerations and complications of this technique. MATERIALS AND METHODS: We performed a retrospective review of patients undergoing intracranial meningioma resection at our institution (March 2001 to December 2012). Comparisons were made between embolized and nonembolized patients, including patient and tumor characteristics, embolization method, operative blood loss, complications, and extent of resection. Logistic regression analyses were used to identify factors predictive of operative blood loss and extent of resection. RESULTS: Preoperatively, 224 patients were referred for embolization, of which 177 received embolization. No complications were seen in 97.1%. There were no significant differences in operative duration, extent of resection, or complications. Estimated blood loss was higher in the embolized group (410 versus 315 mL, P=.0074), but history of embolization was not a predictor of blood loss in multivariate analysis. Independent predictors of blood loss included decreasing degree of tumor embolization (P=.037), skull base location (P=.005), and male sex (P=.034). Embolization was not an independent predictor of gross total resection. CONCLUSIONS: Preoperative embolization is a safe option for selected meningiomas. In our series, embolization did not alter the operative duration, complications, or degree of resection, but the degree of embolization was an independent predictor of decreased operative blood loss.

Effect of DNA damage response by quinazolinone analogue HMJ-38 on human umbilical vein endothelial cells: evidence for γH2A.X and DNA-PK-dependent pathway.

The present study aims to explore the mechanism of quinazolinone analogue HMJ-38-induced DNA damage in endothelial cells in vitro. We attempt to evaluate the antiangiogenetic response utilizing human umbilical vein endothelial cells (HUVECs). Herein, the results demonstrated that HMJ-38 incubation triggered DNA damage behavior and showed a longer DNA migration in HUVECs based on the comet assay and the analysis of DNA agarose gel electrophoresis to contact DNA smears. We further gained to determine a marker of DNA double strand breaks, phosphorylated histone H2A.X (Ser139) (γH2A.X), in HMJ-38-treated HUVECs by flow cytometry and Western blotting assay. We consider that HMJ-38 has caused an increase in γH2A.X, and DNA damage seemed to mediate through DNA-dependent serine/threonine protein kinase (DNA-PK) binding to Ku70/Ku80 as well as advanced activated p-Akt (Ser473) and stimulated phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß) conditions in HUVECs. Importantly, the effect of above DNA damage response was prevented by N-acetyl-l-cysteine (a reactive oxygen species scavenger), and NU7026 (a DNA-PK inhibitor) could attenuate DNA-PK catalytic subunit and phosphorylation of H2A.X on Ser139 expression in comparison with HMJ-38 alone treated HUVECs. Therefore, HMJ-38-provoked DNA damage stress in HUVECs probably led to the activation of γH2A.X/DNA-PK/GSK-3ß signaling. In summary, our novel finding provides more information addressing the pharmacological approach of newly synthesized HMJ-38 for further development and therapeutic application in antiangiogenetic effect of cancer chemotherapy.

Utility of intraoperative angiography during subaxial foramen transversarium decompression for bow hunter's syndrome.

Bow hunter's syndrome is an uncommon cause of vertebrobasilar insufficiency resulting from rotational compression of the extracranial vertebral artery. While positional compression of any portion of the extracranial vertebral artery has been reported to result in bow hunter's syndrome, the most common site of compression is the V2 segment as it passes through the foramen transversarium of the subaxial cervical spine. A 43-year-old woman presented with increasingly frequent pre-syncopal and syncopal episodes upon leftward head rotation. Pre-operative angiographic studies with the neck rotated to the left demonstrated occlusion of the left vertebral artery by a C4-5 osteophyte arising from the C4 uncinate process. The patient underwent microsurgical decompression of the vertebral artery at C4-5 through a standard anterior transcervical retropharyngeal approach. Selective vertebral artery intraoperative angiography performed with the head passively rotated to the left before and after left vertebral artery decompression showed marked improvement in the luminal diameter and blood flow. The patient's symptoms resolved post-operatively. This case illustrates the second instance of intraoperative angiography used to confirm adequate vertebral artery decompression for bow hunter's syndrome. Intraoperative angiography can be safely used to decrease the extent of vertebral artery decompression in order to minimize the risk of operative complications.

Citosol (thiamylal sodium) triggers apoptosis and affects gene expressions of murine leukemia RAW 264.7 cells.

Citosol (thiamylal sodium) is one of generally used anesthetic-sedative agents for clinical patients, and it has not been reported to show induction of cytotoxic effects in cancer cells, especially in mice leukemia RAW 264.7 cells in vitro. In the present study, we investigated the cytotoxic effects of citosol on mice leukemic RAW 264.7 cells, including the effects on protein and gene expression levels which are determined by Western blotting and DNA microarray methods, respectively. Results indicated that citosol induced cell morphological changes, cytotoxic effect, and induction of apoptosis in RAW 264.7 cells. Western blotting analysis demonstrated that citosol promoted the levels of Fas, cytochrome c, caspase 9 and 3 active form and Bax levels, but it suppressed Bcl-xl protein level that may lead to apoptotic death in RAW 264.7 cells. Furthermore, DNA microarray assay indicated that citosol significantly promoted the expression of 5 genes (Gm4884, Gm10883, Lce1c, Lrg1, and LOC100045878) and significantly inhibited the expression of 24 genes (Gm10679, Zfp617, LOC621831, Gm5929, Snord116, Gm3994, LOC380994, Gm5592, LOC380994, LOC280487, Gm4638, Tex24, A530064D06Rik, BC094916, EG668725, Gm189, Hist2h3c2, Gm8020, Snord115, Gm3079, Olfr198, Tdh, Snord115, and Olfr1249). Based on these observations, citosol induced cell apoptosis and influenced gene expression in mice leukemia RAW 264.7 cells in vitro.

Evaluation of the impact of HIV serostatus, tobacco smoking and CD4 counts on epidermoid anal cancer survival.

Tobacco smoking and HIV infection increase the risk of epidermoid anal cancer (EAC). No published studies have examined smoking and EAC outcomes, and the literature is discrepant regarding outcomes of HIV-positive patients with EAC. The goal of this study was to examine smoking history, HIV status and outcomes in EAC patients. We conducted a retrospective analysis of adults with invasive EAC treated in the University of Washington hospital system from 1 January 1994 to 31 December 2008. Sixty-three patients were included. Forty-seven patients (75%) had primary chemoradiation, of whom 42 (89%) completed therapy. Two patients (3%) received radiotherapy alone. Fourteen patients (22%) underwent primary surgery, of whom 11 (79%) underwent tumour excision and three (21%) abdominoperineal resection (APR). We analysed smoking history, HIV status and CD4 count (≥ 200 cells/µL/<200 cells/µL for HIV-positive patients) versus outcomes. Forty-five patients (71%) were in remission, and 44 (70%) were alive at last follow-up. Overall survival was significantly better for never-smokers than for ever-smokers. There were no differences in outcomes according to HIV status or CD4 counts. Patients with anal cancer who smoke have worse overall survival than non-smoking patients. HIV infection does not appear to affect anal cancer outcomes.

Drug eluting stents for symptomatic intracranial and vertebral artery stenosis.

The use of bare metal stents (BMS) to prevent recurrent stroke due to stenosis of the cerebral vasculature is associated with high rates of restenosis. Drug-eluting stents (DES) may decrease this risk. We evaluated the performance of DES in a cohort of patients treated at our institution.Consecutive patients treated with DES were identified by a case log and billing records; data regarding procedural details, clinical outcome and angiographic follow-up was obtained by retrospective chart review.Twenty-six patients (27 vessels; 14 vertebral origin (VO); 13 intracranial) were treated. Stenosis was reduced from mean 81% to 8% at the VO and 80% to 2% intracranially. No strokes occurred in the first 24 hours after stenting or at any time point in the VO group during a mean follow-up period of nine months. Among patients with intracranial stents, stroke with permanent disability occurred within 30 days in 1/12 (8%) and after 30 days in 1/11 (9%) with clinical follow-up (mean follow-up, 14 months). Follow-up catheter angiography was obtained in 14/14 (100%) in the VO group at mean eight months and in 8/11 surviving patients (73%) at a mean of ten months after stenting in the intracranial group. The restenosis rate was 21% at the VO (3/14) and 38% (3/8) for intracranial stents. Restenosis at the VO was less frequent than might have been expected from reports utilizing BMS, however, overall restenosis rates appeared higher than previously reported for patients with intracranial DES and comparable with restenosis rates for intracranial BMS.

Femoral artery complications associated with the Mynx closure device.

BACKGROUND AND PURPOSE: Devices to close a femoral arteriotomy are frequently used after catheterization for interventional radiology and cardiac procedures to decrease the time to hemostasis and ambulation and, potentially, to decrease local complications. The Mynx vascular closure device uses a sealant designed to occlude the access tract, resulting in hemostasis. MATERIALS AND METHODS: We retrospectively reviewed all cases in which the Mynx device was used and for which follow-up angiography was available. A total of 146 devices were deployed in 135 patients. A follow-up vascular study visualizing the femoral artery was performed in 26 patients (27 studies). RESULTS: There were 5 (5/27, 18%) cases of intravascular Mynx sealant on follow-up vascular imaging. Three pseudoaneurysms (3/27, 11%) were identified. CONCLUSIONS: In this small study, intravascular sealant and pseudoaneurysms were found frequently after femoral arterial closure with the Mynx vascular closure device.

The porphyrin-fullerene nanoparticles to promote the ATP overproduction in myocardium: 25Mg2+-magnetic isotope effect.

This is a first case ever reported on the fullerene-based low toxic nanocationite particles (porphyrin adducts of cyclohexyl fullerene-C(60)) designed for targeted delivery of the paramagnetic magnesium stable isotope to the heart muscle providing a sharp clinical effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 h after a single injection (0.03-0.1 LD(50)). A whole principle of this therapy is novel: (25)Mg(2+)-magnetic isotope effect selectively stimulates the ATP overproduction in the oxygen-depleted cells due to (25)Mg(2+) released by the nanoparticles. Being membranotropic cationites, these "smart nanoparticles" release the overactivating paramagnetic cations only in response to the metabolic acidic shift. The resulting positive changes in the heart cell energy metabolism may help to prevent and/or treat the local myocardial hypoxic disorders and, hence, protect the heart muscle from a serious damage in a vast variety of the hypoxia-caused clinical situations including both doxorubicin and 1-methylnicotineamide cardiotoxic side effects. Both pharmacokinetics and pharmacodynamics of the drug proposed make it suitable for safe and efficient administration in either single or multi-injection (acute or chronic) therapeutic schemes.

Cyclopeptide alkaloids from stems of Paliurus ramossisimus.

Three 13-membered cyclopeptide alkaloids, paliurines G, H and I, together with six known alkaloids, nummularine H, daechuine-S3, paliurines A-C and F, were isolated from the stem of Paliurus ramossisimus by a combination of centrifugal partition chromatography and preparative TLC. Their structures were characterized and established on the basis of spectral analysis. A preliminary study indicated that nummularine H could shorten the methohexital induced sleeping time.

Chemical constituents from Drypetes littoralis.

Chemical investigation of Drypetes littoralis yielded three new tricyclic diterpenes, drypetenones A, B, and C (1--3), and one new xanthone (4). Spectral analyses and chemical correlations established the structures as 10S-12-hydroxy-11-methoxy-13-methylpodocarpa-1,5,8,11,13-pentaene-3,7-dione, (1), 10S-12-hydroxy-11-methoxy-13-methylpodocarpa-5,8,11,13-tetraene-3,7-dione (2), 10S-12-hydroxy-6,11-dimethoxy-13-methylpodocarpa-1,5,8,11,13-pentaene-3,7-dione (3), and 1-hydroxy-7-hydroxymethyl-6-methoxyxanthone (4). Complete (13)C NMR assignment of boehmenan D (5) is also made.

Characterization of the murine Lbx2 promoter, identification of the human homologue, and evaluation as a candidate for Alström syndrome.

The murine Lbx2 gene is a member of the ladybird family of homeobox genes, which is expressed in the developing urogenital system, eye, and brain. Using transgenic mice, we demonstrate that 9 kb of the 5' flanking region of mouse Lbx2 is able to direct expression of a reporter gene in a tissue-specific manner recapitulating the endogenous expression pattern. This regulatory region provides a novel reagent allowing for transgenic expression in the developing urogenital ridge. In addition, we describe the identification of the human homologue, LBX2. Comparison of the human LBX2 and mouse Lbx2 sequences upstream of the coding regions reveals sequence conservation suggesting conserved regulatory regions. Both the human LBX2 and the mouse Lbx2 genes have similar genomic structures and are composed of two exons separated by an intron. We mapped the mouse Lbx2 gene to 35 cM on chromosome 6 and the human LBX2 gene to a homologous region of chromosome 2p13. This is a candidate region for several inherited disorders, including Alström syndrome, a disorder that includes ocular, urogenital, and renal abnormalities. Given the expression pattern of Lbx2, the chromosomal location in humans, and the potential function of mammalian ladybird genes, we have begun to analyze patients with ocular disorders and those with Alström syndrome for mutations in LBX2. Although polymorphisms were identified, our results indicate that mutations in the coding region of LBX2 do not account for Alström syndrome in the six kindreds analyzed.

Cyclopeptide alkaloids from Paliurus ramossisimus.

Seven zizyphine A-type cyclopeptide alkaloids were isolated from the roots of Paliurus ramossisimus by the combination of centrifugal partition chromatography and conventional separation methods. The novel structures of paliurines A-F (1-6) were characterized and established on the basis of MS and elaborate NMR spectral analyses. Terminal dipeptide stereochemistry was confirmed by correlation with the synthetic dipeptides via comparison of their (13)C NMR data.

Lbx2, a novel murine homeobox gene related to the Drosophila ladybird genes is expressed in the developing urogenital system, eye and brain.

We describe the cloning, expression pattern, and genomic organization of Lbx2, a murine homologue of the Drosophila and mammalian ladybird genes. Lbx2 includes a homeodomain motif most closely related to those of Lbx1 and the Drosophila ladybird proteins. Lbx2 transcripts are first detected at E10.5 when they are located in the gonadal component of the urogenital ridge. Expression of Lbx2 dramatically increases by E11.5 in the urogenital ridges, and in the cranial surface ectoderm. At later stages, Lbx2 transcripts are expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands. From E14.5 to birth, Lbx2 expression is evident in the developing retinal neuroepithelium and the vibrissa.

Transgenic rescue of congenital heart disease and spina bifida in Splotch mice.

Pax3-deficient Splotch mice display neural tube defects and an array of neural crest related abnormalities including defects in the cardiac outflow tract, dorsal root ganglia and pigmentation. Pax3 is expressed in neural crest cells that emerge from the dorsal neural tube. Pax3 is also expressed in the somites, through which neural crest cells migrate, where it is required for hypaxial muscle development. Homozygous mutant Splotch embryos die by embryonic day 14. We have utilized the proximal 1.6 kb Pax3 promoter and upstream regulatory elements to engineer transgenic mice reproducing endogenous Pax3 expression in neural tube and neural crest, but not the somite. Over expression of Pax3 in these tissues reveals no discernible phenotype. Breeding of transgenic mice onto a Splotch background demonstrates that neural tube and neural crest expression of Pax3 is sufficient to rescue neural tube closure, cardiac development and other neural crest related defects. Transgenic Splotch mice survive until birth at which time they succumb to respiratory failure secondary to absence of a muscular diaphragm. Limb muscles are also absent. These results indicate that regulatory elements sufficient for functional expression of Pax3 required for cardiac development and neural tube closure are contained within the region 1.6 kb upstream of the Pax3 transcriptional start site. In addition, the single Pax3 isoform used for this transgene is sufficient to execute these developmental processes. Although the extracellular matrix and the environment of the somites through which neural crest migrates is known to influence neural crest behavior, our results indicate that Pax3-deficient somites are capable of supporting proper neural crest migration and function suggesting a cell autonomous role for Pax3 in neural crest.

Antiviral tannins from two Phyllanthus species.

Seven ellagitannins isolated from Phyllanthus myrtifolius and P. urinaria (Euphorbiaceae) have been shown, for the first time, to be active against Epstein-Barr virus DNA polymerase (EBV-DP) at the microM level. All these compounds have the same moiety of a corilagin, and differ from each other by different substitutions at C-2 and C-4 of the glucose core. SAR analysis and molecular modeling reveal that the essential pharmacophore of these tannins resides in the corilagin moiety. The outer complex carboxylic acid moieties appear to act only as auxopharmacore.