Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects.

BACKGROUND: SHEN26, an oral broad-spectrum antiviral drug, possesses potent preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a favorable safety profile. METHODS: We report safety, tolerability, and pharmacokinetic data from a randomized, double-blind, placebo-controlled phase I study of SHEN26. Eighty-six healthy subjects were enrolled in the three studies: a single ascending-dose study (SAD), a multiple ascending-dose study (MAD), and a food-effect study (FE). RESULTS: In the SAD trial, the maximum observed plasma concentration (Cmax) and area under the curve (AUC) of the SHEN26 rapid metabolite SHEN26-69-0 increased approximately dose-proportionally in the 50-400 mg fasting dose range. In the 800 mg dose group, standard meals increased the Cmax and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of Cmax and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (Tmax) and increased the Cmax and AUC of SHEN26-69-0 compared with fasting administration. Most treatment-related adverse events were mild and resolved without treatment. CONCLUSION: SHEN26 demonstrated satisfactory safety and tolerability in healthy subjects, which supports the continued study of SHEN26 against SARS-CoV-2. TRIAL REGISTRATION: The trial is registered in ClinicalTrials.gov (CT. gov identifier: NCT05504746).

Curcumin Inhibits the Growth of Hepatocellular Carcinoma via the MARCH1-mediated Modulation of JAK2/STAT3 Signaling.

BACKGROUND: Curcumin has been reported to have anti-hepatocellular carcinoma (HCC) effects, but the underlying mechanism is not well known. OBJECTIVES: To investigate whether membrane-associated RING-CH 1 (MARCH1) is involved in the curcumin-induced growth suppression in HCC and its underlying molecular mechanism. A few recent patents for curcumin for cancer are also reviewed in this article. METHODS: The effect of curcumin on growth inhibition of HCC cells was analyzed through in vitro and in vivo experiments, and the expression levels of MARCH1, Bcl-2, VEGF, cyclin B1, cyclin D1, and JAK2/STAT3 signaling molecules were measured in HCC cells and the xenograft tumors in nude mice. Cell transfection with MARCH1 siRNAs or expression plasmid was used to explore the role of MARCH1 in the curcumin-induced growth inhibition of HCC cells. RESULTS: Curcumin inhibited cell proliferation, promoted apoptosis, and arrested the cell cycle at the G2/M phase in HCC cells with the decrease of Bcl-2, VEGF, cyclin B1, and cyclin D1 expression as well as JAK2 and STAT3 phosphorylation, resulting in the growth suppression of HCC cells. MARCH1 is highly expressed in HCC cells, and its expression was downregulated after curcumin treatment in a dose-dependent manner. The knockdown of MARCH1 by siRNA decreased the phosphorylation levels of JAK2 and STAT3 and inhibited the growth of HCC cells. In contrast, opposite results were observed when HCC cells overexpressed MARCH1. A xenograft tumor model in nude mice also showed that curcumin downregulated MARCH1 expression and decelerated the growth of transplanted HCC with the downregulation of JAK2/STAT3 signaling and functional molecules. The ADC value of MRI analysis showed that curcumin slowed down the progression of HCC. CONCLUSION: Our results demonstrated that curcumin may inhibit the activation of JAK2/STAT3 signaling pathway by downregulating MARCH1 expression, resulting in the growth suppression of HCC. MARCH1 may be a novel target of curcumin in HCC treatment.

Isolation, identification, and induced differentiation of satellite cells from skeletal muscle of adult tree shrews.

A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an "S"-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.

Generation of a gene-corrected isogenic iPSC cell line from an X-linked retinoschisis patient with a hemizygous mutation c.304C > T (p.R102W) in RS1 gene.

X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS.

Corneal biomechanics after small incision lenticule extraction and femtosecond laser in situ keratomileusis: A systematic review and meta-analysis.

BACKGROUND: Small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK) have been extensively studied as the main surgical methods for corneal refractive surgery. However, there is no consensus on whether SMILE is superior to FS-LASIK in corneal biomechanics. Therefore, this systematic review and meta-analysis used the results of ocular response analyzer and corvis ST to explore whether SMILE is superior to FS-LASIK in corneal biomechanics. METHODS: The literature was searched in PubMed, EMBASE, and Controlled Trials Register databases. The Cochrane Collaboration's "risk of bias" tool was used to evaluate the quality of the included randomized clinical trials, and the Newcastle-Ottawa Scale was used to evaluate the included non-randomized controlled trials. The results were analyzed using Revman 5.3. RESULTS: Sixteen studies (3 randomized clinical trials and 13 non-randomized controlled trials) were included in this meta-analysis. There was no statistical difference in corneal biomechanics between SMILE and FS-LASIK in corneal hysteresis [mean difference (MD), 0.20; 95% confidence interval (CI): -0.09, 0.49; P = .18] and corneal resistant factor (MD, 0.31; 95% CI: -0.09, 0.71; P = .13), A1 time (MD, -0.02; 95% CI: -0.11, 0.07; P = .66), A1 length (MD, 0.01; 95% CI: -0.01, 0.03; P = .42), A1 velocity (MD, 0.00; 95% CI: -0.01, 0.01; P = .85), A2 velocity (MD, -0.01; 95% CI: -0.11, 0.09; P = .86), HC time (MD, 0.12; 95% CI: -0.13, 0.38; P = .35), The stiffness parameter at first applanation (MD, -7.91; 95% CI: -17.96, 2.14; P = .12), The ratio between the deformation amplitude 2 mm away from apex and the apical deformation (MD, 0.01; 95% CI: -0.26, 0.27; P = .96). CONCLUSION: A comprehensive assessment of the parameters of ocular response analyzer and corvis ST showed that SMILE is not superior to LASIK in corneal biomechanics 3 months post-surgery.

Review of research on migration, distribution, biological effects, and analytical methods of microfibers in the environment.

Microplastics have been proven to be one of the critical environmental pollution issues. Moreover, microfibers, the most prominent form of microplastics in the environment, have likewise attracted the attention of various countries. With the increase in global population and industrialization, the production and use of fibers continue to increase yearly. As a result, a large number of microfibers are formed. If fiber products are not used or handled correctly, it will cause direct/indirect severe microfiber environmental pollution. Microfibers will be further broken into smaller fiber fragments when they enter the natural environment. Presently, researchers have conducted extensive research in the identification of microfibers, laying the foundation for further resourcefulness research. This work used bibliometric analysis to review the microfiber contamination researches systematically. First, the primary sources of microfibers and the influencing factors are analyzed. We aim to summarize the influence of the clothing fiber preparation and care processes on microfiber formation. Then, this work elaborated on the migration in/between water, atmosphere, and terrestrial environments. We also discussed the effects of microfiber on ecosystems. Finally, microfibers' current and foreseeable effective treatment, disposal, and resource utilization methods were explained. This paper will provide a structured reference for future microfiber research.

Multi-Scale Feature Fusion Convolutional Neural Network for Indoor Small Target Detection.

The development of object detection technology makes it possible for robots to interact with people and the environment, but the changeable application scenarios make the detection accuracy of small and medium objects in the practical application of object detection technology low. In this paper, based on multi-scale feature fusion of indoor small target detection method, using the device to collect different indoor images with angle, light, and shade conditions, and use the image enhancement technology to set up and amplify a date set, with indoor scenarios and the SSD algorithm in target detection layer and its adjacent features fusion. The Faster R-CNN, YOLOv5, SSD, and SSD target detection models based on multi-scale feature fusion were trained on an indoor scene data set based on transfer learning. The experimental results show that multi-scale feature fusion can improve the detection accuracy of all kinds of objects, especially for objects with a relatively small scale. In addition, although the detection speed of the improved SSD algorithm decreases, it is faster than the Faster R-CNN, which better achieves the balance between target detection accuracy and speed.

Dysbiosis and Implication of the Gut Microbiota in Diabetic Retinopathy.

The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The α and ß diversities in both the DM and DR groups were reduced compared with those in the HC group. Blautia was the most abundant genus, especially in the DM group. In addition, increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia-Shigella, Faecalibacterium, Eubacterium_hallii_group and Clostridium genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, Pasteurellaceae, which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.

Focus properties of cosh-Gaussian beams with the power-exponent-phase vortex.

Vector diffraction theory is used to investigate the focusing properties of cosh-Gaussian beams with the power-exponent-phase vortex. The effects of the decentered parameter, the power order, and the topological charge on the normalized intensity distribution are examined. Results show that intensity distribution in the focal region can be altered significantly by the topological charge, the power order, and the decentered parameter. The pattern of the optical intensity slowly enlarges with the increase of topological charge. The strongest intensity part of the annulus rotates by the changing topological charge. As the power order increases, the intensity distribution is more concentrated. As the decentered parameter increases, there occur multiple relatively strong intensity peaks, and the entire focus pattern extends outward. Some optical gradient force distributions are investigated to illuminate the applications of these alterable foci patterns.

Expression and clinical value of lncRNA MALAT1 and lncRNA ANRIL in glaucoma patients.

Expression and clinical value of long non-coding RNA (lncRNA) MALAT1 and lncRNA ANRIL in glaucoma patients were investigated. Altogether 86 glaucoma patients who were diagnosed (study group) and 86 people who underwent physical examinations and were confirmed to be healthy (control group) in the Hospital of Chengdu University of Traditional Chinese Medicine from January 2016 to June 2018 were enrolled. Expression of the serum lncRNA MALAT1, lncRNA ANRIL, pigment epithelium-derived factor (PEDF), homocysteine (Hcy), and inflammatory cytokines [interleukin-12 (IL-12), interleukin-4 (IL-4) and interferon-γ (IFN-γ)] was detected. The clinical significance of lncRNA MALAT1 and lncRNA ANRIL was analyzed. Compared with those in the control group, patients in the study group had significantly lower expression of serum lncRNA MALAT1 and lncRNA ANRIL (P<0.05), significantly lower expression of serum PEDF and IL-12 (P<0.05), and significantly higher expression of serum Hcy and IL-4 (P<0.05), without significant difference in the expression of serum IFN-γ between the two groups (P>0.05). Serum lncRNA MALAT1 and lncRNA ANRIL were positively correlated with PEDF and IL-12 (P<0.05), but negatively correlated with Hcy and IL-4 (P<0.05). The diagnostic value of the combined detection of lncRNA MALAT1 and lncRNA ANRIL was higher than that of lncRNA MALAT1 alone and lncRNA ANRIL alone. The expression of lncRNA MALAT1 and lncRNA ANRIL was significantly related to the pathological staging of the patients (P<0.05), not the sex, age, body mass index (BMI), types, and presence or absence of myopia (P>0.05). lncRNA MALAT1 and lncRNA ANRIL are poorly expressed in the serum of glaucoma patients and related to the patients' conditions. Their combined detection has high diagnostic value for the disease. Therefore, they may be used as new molecular targets for the diagnosis and severity evaluation of glaucoma patients.

Effective tensor approach for simulating the propagation of partially coherent Hermite-sinh-Gaussian beams through an ABCD optical system in turbulent atmosphere.

An efficient tensor approach is used to simulate the propagation of partially coherent Hermite-sinh-Gaussian (H-ShG) beams through an ABCD optical system in a turbulent atmosphere. Analytical expressions for the average intensity are derived. The properties of the average intensity of the beam are studied numerically. It is found that the average intensity distribution of the beam is almost independent of the structure constant of turbulence when the spatial coherence length is very small and the beam with larger spatial coherence length is less affected by the turbulent atmosphere. Moreover, the transition from an H-ShG beam into a Gaussian beam becomes quicker with smaller beam order and smaller Sh parameters.

Air tamponade in retinal detachment surgery followed by ultra-widefield fundus imaging system.

AIM: To report the surgical result of pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD) by ultra-widefield fundus imaging system. METHODS: Of 25 consecutive patients (25 eyes) with fresh primary RRD and causative retinal break and vitreous traction were presented. All the patients underwent PPV with air tamponade. Visual acuity (VA) was examined postoperatively and images were captured by ultra-widefield scanning laser ophthalmoscope system (Optos). RESULTS: Initial reattachment was achieved in 25 cases (100%). The air volume was >60% on the postoperative day (POD) 1. The ultra-widefield images showed that the retina was reattached in all air-filled eyes postoperatively. The retinal break and laser burns in the superior were detected in 22 of 25 eyes (88%). A missed retinal hole was found under intravitreal air bubble in 1 case (4%). The air volume was range from 40% to 60% on POD 3. A double-layered image was seen in 25 of 25 eyes with intravitreal gas. Retinal breaks and laser burns around were seen in the intravitreal air. On POD 7, small bubble without effect was seen in 6 cases (24%) and bubble was completely disappeared in 4 cases (16%). Small oval bubble in the superior area was observed in 15 cases (60%). There were no missed and new retinal breaks and no retinal detachment in all cases on the POD 14 and 1mo and last follow-up. Air disappeared completely on a mean of 9.84d postoperatively. The mean final postoperative best-corrected visual acuity (BCVA) was 0.35 logMAR. Mean final postoperative BCVA improved significantly relative to mean preoperative (P<0.05). Final VA of 0.3 logMAR or better was seen in 13 eyes. CONCLUSION: PPV with air tamponade is an effective management for fresh RRD with superior retinal breaks. The ultra-widefield fundus imaging can detect postoperative retinal breaks in air-filled eyes. It would be a useful facility for follow-up after PPV with air tamponade. Facedown position and acquired visual rehabilitation may be shorten.

[Effects of subcutaneous embedding of thumb-tack needle on tear film in patients with dry eye].

OBJECTIVE: To observe the effects of subcutaneous embedding of thumb-tack needle combined with mytear and simple mytear on tear film in patients with dry eye. METHODS: Eighty patients of dry eye (160 eyes) were randomly divided into an observation group and a control group, 40 cases in each group. The 0.1% sodium hyaluronate eye drop (alice) was applied in the control group, four times per day for two weeks. On the basis of the control group, the subcutaneous embedding of thumb-tack needle was used at ① Cuanzhu (BL 2), Sizhukong (SJ 23), Sibai (ST 2), ② Yintang (EX-HN 3), Yuyao (EX-HN 4), Taiyang (EX-HN 5). The two groups of acupoints were used alternately. The thumb-tack needle was placed for 2 to 3 days, once a week for two weeks. The subjective symptom score, Schirmer Ⅰ test (SⅠT), tear break-up time (BUT) and corneal fluorescein staining (CFS) were compared before treatment, after treatment and during 2-week follow-up visit in the two groups. The effects of the two groups were compared. RESULTS: Compared before treatment, the subjective symptom score and CFS were reduced but SⅠT and BUT were increased after treatment and during follow-up visit in the two groups (all P<0.05), which in the observation group were superior to those in the control group (all P<0.05). The total effective rate was 90.0% (36/40) in the observation group, which was superior to 85.0% (34/40) in the control group (P<0.05). CONCLUSION: The subcutaneous embedding of thumb-tack needle could increase the amount of SIT, prolong BUT and repair pathological damage of cornea, which could relieve the symptoms of dry eye and improve visual quality.

Generation of an iPS cell line via a non-integrative method using urine-derived cells from a patient with USH2A-associated retinitis pigmentosa.

We have established an induced pluripotent stem (iPS) cell line using urine-derived cells from a 27-year-old male patient with retinitis pigmentosa associated with point mutations in the USH2A gene. Feeder-free culture conditions and the integration-free CytoTune™-iPS 2.0 Sendai Reprogramming Kit were used.

Reduced Macular Vascular Density in Myopic Eyes.

BACKGROUND: Morphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography. METHODS: This cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis. RESULTS: Both superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (ß = -0.850 and 0.460, respectively) and deep (ß = -0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (ß = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in optic disc region had no difference among the three groups, and it was not associated with AL, spherical equivalent, or RNFL thickness. CONCLUSION: Our results suggested that with the increase of myopia, the vascular density decreased in macular region, but not in optic disc region.

Associated factors for visibility and width of retrobulbar subarachnoid space on swept-source optical coherence tomography in high myopia.

Subarachnoid space (SAS) around optic nerve can be visible with swept-source optical coherence tomography (SS-OCT). However, the relevant factors for its visibility and width have not been reported. In this prospective study, 193 eyes with high myopia were evaluated by SS-OCT. The relationship between age, gender, axial length, optic disc area, parapapillary atrophy (PPA) area, peripapillary choroidal thickness with the visibility and width of SAS were assessed. The results showed that SAS was observed in 125 (64.8%) and not observed in 68 (35.2%) eyes. Visibility of SAS is associated with long axial length, high myopia, thin choroid, large PPA and large optic disc areas. Among these associations, PPA area was the only independent factor (b = 0.177, p < 0.001). The width of SAS was associated with thin choroid, long axial length, large optic disc area and large PPA area. Multivariant analysis showed that optic disc area and PPA area were independent factors for the width of SAS (b = 30.8, p = 0.016 and 16.2, p < 0.001 respectively). These results suggested that SAS was extended into the peripapillary region possibly due to extension of posterior sclera in high myopia.

New Biogeographic insight into Bauhinia s.l. (Leguminosae): integration from fossil records and molecular analyses.

BACKGROUND: Given that most species that have ever existed on earth are extinct, it stands to reason that the evolutionary history can be better understood with fossil taxa. Bauhinia is a typical genus of pantropical intercontinental disjunction among the Asian, African, and American continents. Geographic distribution patterns are better recognized when fossil records and molecular sequences are combined in the analyses. Here, we describe a new macrofossil species of Bauhinia from the Upper Miocene Xiaolongtan Formation in Wenshan County, Southeast Yunnan, China, and elucidate the biogeographic significance through the analyses of molecules and fossils. RESULTS: Morphometric analysis demonstrates that the leaf shapes of B. acuminata, B. championii, B. chalcophylla, B. purpurea, and B. podopetala closely resemble the leaf shapes of the new finding fossil. Phylogenetic relationships among the Bauhinia species were reconstructed using maximum parsimony and Bayesian inference, which inferred that species in Bauhinia species are well-resolved into three main groups. Divergence times were estimated by the Bayesian Markov chain Monte Carlo (MCMC) method under a relaxed clock, and inferred that the stem diversification time of Bauhinia was ca. 62.7 Ma. The Asian lineage first diverged at ca. 59.8 Ma, followed by divergence of the Africa lineage starting during the late Eocene, whereas that of the neotropical lineage starting during the middle Miocene. CONCLUSIONS: Hypotheses relying on vicariance or continental history to explain pantropical disjunct distributions are dismissed because they require mostly Palaeogene and older tectonic events. We suggest that Bauhinia originated in the middle Paleocene in Laurasia, probably in Asia, implying a possible Tethys Seaway origin or an "Out of Tropical Asia", and dispersal of legumes. Its present pantropical disjunction resulted from disruption of the boreotropical flora by climatic cooling after the Paleocene-Eocene Thermal Maximum (PETM). North Atlantic land bridges (NALB) seem the most plausible route for migration of Bauhinia from Asia to America; and additional aspects of the Bauhinia species distribution are explained by migration and long distance dispersal (LDD) from Eurasia to the African and American continents.

[Protein and mRNA expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of leukemia patients and its correlation with clinical features].

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.

The influence of high glucose on the Cip/Kip family expression profiles in HRECs.

Neovascularization is the main characteristic of the proliferative stage of diabetic retinopathy. It has been proven that cell cycle regulation is involved in angiogenesis. The cell cycle regulators, Cip/Kip protein family, belong to the cyclin-dependent kinase inhibitors, are versatile proteins, and except for their function in cell cycle regulation, they also participate in transcription, apoptosis and migration. The expression profiles of the Cip/Kip family in human retina microvascular endothelial cells (HRECs) under normal or high glucose conditions has not been described before. This study was undertaken to determine the expression profiles of the Cip/Kip family proteins, e.g., proteins which are influenced by high glucose and in what manner. Western blot and immunofluorescence analyses were used to investigate the protein expression profiles. Only p21(cip1) and p27(kip1) were detected in HRECs, and they were located in the nucleus. P21(cip1) protein abundance was higher than p27(kip1) in HRECs. Incubation of HRECs in medium containing 30 mM D-glucose for 48 h resulted in downregulation of p21(cip1) protein expression, but had no influence on p27(kip1) protein levels or p21(cip1) mRNA abundance. These results were accompanied by cell cycle G1 phase exit and a lower cell survival rate. Our data show for the first time that high glucose changes the Cip/Kip family expression profiles in HRECs, which may be the foundation for the investigation of the role of the Cip/Kip family in the pathogenesis of diabetic retinopathy.