Tumor-Associated CD163+ M2 Macrophage Infiltration is Highly Associated with PD-L1 Expression in Cervical Cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. METHODS: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. RESULTS: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p<0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p<0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p<0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD163+ macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). CONCLUSION: CD163+ M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target.

A Survey on Intelligent Screening for Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of vision loss and can be effectively avoided by screening, early diagnosis and treatment. In order to increase the universality and efficiency of DR screening, many efforts have been invested in developing intelligent screening, and there have been great advances. In this paper, we survey DR screening from four perspectives: 1) public color fundus image datasets of DR; 2) DR classification and related lesion-extraction approaches; 3) existing computer-aided systems for DR screening; and 4) existing issues, challenges, and research trends. Our goal is to provide insights for future research directions on DR intelligent screening.

Design and synthesis of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships.

Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound 10d, which exhibits approximate potency on CDK4/6 (IC50 = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound 10d could be a promising candidate and a good starting point as anticancer drugs.

CrGNAT gene regulates excess copper accumulation and tolerance in Chlamydomonas reinhardtii.

Excess copper (Cu) in environment affects the growth and metabolism of plants and green algae. However, the molecular mechanism for regulating plant tolerance to excess Cu is not fully understood. Here, we report a gene CrGNAT enconding an acetyltransferase in Chlamydomonas reinhardtii and identified its role in regulating tolerance to Cu toxicity. Expression of CrGNAT was significantly induced by 75-400µM Cu. The top induction occurred at 100µM. Transgenic algae overexpressing CrGNAT (35S::CrGNAT) in C. reinhardtii showed high tolerance to excess Cu, with improved cell population, chlorophyll accumulation and photosynthesis efficiency, but with low degree of oxidation with regard to reduced hydrogen peroxide, lipid peroxides and non-protein thiol compounds. In contrast, CrGNAT knock-down lines with antisense led to sensitivity to Cu stress. 35S::CrGNAT algae accumulated more Cu and other metals (Zn, Fe, Cu, Mn and Mg) than wild-type, whereas the CrGNAT down-regulated algae (35S::AntiCrGNAT) had moderate levels of Cu and Mn, but no effects on Zn, Fe and Mg accumulation as compared to wild-type. The elevated metal absorption in CrGNAT overexpression algae implies that the metals can be removed from water media. Quantitative RT-PCR analysis revealed that expression of two genes encoding N-lysine histone methyltransferases was repressed in 35S::CrGNAT algae, suggesting that CrGNAT-regulated algal tolerance to Cu toxicity is likely associated with histone methylation and chromatin remodeling. The present work provided an example a basis to develop techniques for environmental restoration of metal-contaminated aquatic ecosystems.

DNA ploidy of cervical epithelial cells should be a cure criterion of high-risk HPV infection in Xinjiang Uygur women.

BACKGROUND: The Uygur women have the highest incidence of cervical cancer in all Chinese ethnic groups. The research was conducted to explore whether DNA ploidy could be the prognostic indicator of human papillomavirus (HPV) infection in Xinjiang Uygur women. METHODS: Case data and cervical exfoliated cell samples from 326 Uygur women. The DNA ploidy was analyzed by flow cytometry. The flow-through hybridization and gene chip (FHGC) for HPV type test then divided the cases into negative HPV group, non high-risk HPV infection group, single high-risk HPV infection group, and multiple high-risk HPV infection group. Lastly, 113 cases from 273 HPV infection cases were followed up. RESULTS: The 16-type HPV had the highest rate in all genotypes infection; 16/18-type HPV mixed infection was the most common type in multiple high-risk HPV infection group. Abnormal DNA ploidy happened along with the seriousness of HPV infection. Compared with the HPV negative group, DNA heteroploid appeared 12.750 times and 22.705 times, respectively, in single high-risk HPV and multiple high-risk HPV infection groups. Followed up 1 year later, the DNA index, S-phase cells' peak percentage and heteroploid of cervical exfoliated cells significantly reduced in single and multiple high-risk HPV infection patients, but in nine patients negative HPV infection and DNA heteroploid still existed. CONCLUSION: The finally cure criterion of high-risk HPV infection should include the negative HPV test and normal DNA ploidy analysis. It was useful to prevent and cure cervical lesions in Xinjiang Uygur women through high-risk HPV test and DNA ploidy analysis. The transient infection and persistent infection in Xinjiang Uygur women should be taken as further research.

[Danhong injection, ligustrazine injection, combined adsorbable biomembranes prevented adhesion of tendons after the repair operation: a clinical research].

OBJECTIVE: To explore the effect and the mechanism of Danhong Injection (DI), Ligustrazine Injection (LI), and adsorbable biomembranes in preventing the adhesion of tendons and tissues. METHODS: Totally 120 patients all suffering from simple flexor digitorum tendon rupture on the hand zone two damaged by sharp weapons were randomly assigned to Group A (Dikang adsorbable biomembrane), Group B (Tianxinfu adsorbable biomembrane), Group C (Tianxinfu adsorbable biomembrane + Ligustrazine group), and Group D (Tianxinfu adsorbable biomembrane + DI group) in accordance with random digit table, 30 cases in each group. Indicators such as total active movement (TAM) of the hand tendon, Minnesota manual dexterity test (MMDT), and finger flex strength test (FFST) were observed. RESULTS: The TAM and the favorable rate were higher in Group C and D than in Group A and B at post-operative 4 and 8 week (P < 0.05, P < 0.01). There was no statistical difference between Group C and D (P > 0.05). Each index of MMDT was lower in Group C and D than in Group A and B (P < 0.05). There was no statistical difference in FFST among all the 4 groups (P > 0.05). CONCLUSIONS: Combined application of LI or DI with Tianxinfu adsorbable biomembranes could effectively prevent the adhesion of tendons. DI showed equivalent effect as LI did. Besides, the combined application was superior in preventing adhesion to using Xintianfu adsorbable biomembrane or Dikan adsorbable biomembrane alone.

HISN3 mediates adaptive response of Chlamydomonas reinhardtii to excess nickel.

Investigation of genes for heavy metal [e.g. nickel (Ni) and zinc (Zn)] absorption and detoxification in green algae is of great importance because some of the metals have become one of the major contaminants in the aquatic ecosystem. In plants, overload of heavy metals modifies many aspects of biological processes. However, the mechanisms by which heavy metals exert detrimental effects are not fully understood. The present study identified a biological role for HISN3 (the gene coding for phosphoribosylformimino-5-aminoimidazole carboxamide ribonucleotide isomerase) in regulating the response of Chlamydomonas reinhardtii, a unicellular green alga, to Ni toxicity. In higher plants, HISN3 encodes an enzyme catalyzing the fourth step in the histidine biosynthesis pathway, but its functional importance is yet to be identified. Transgenic algae overexpressing HISN3 in C. reinhardtii showed high tolerance to excess Ni, with a 48.3-57.4% increase in cell population and moderate histidine accumulation compared with the wild type. HISN3 overexpression improved accumulation of Chl and photosynthesis efficiency, but suppressed Ni-induced generation of reactive oxygen species and lipid peroxides. Interestingly, more Ni and other metals [Zn, iron (Fe), copper (Cu), manganese (Mn) and magnesium (Mg)] were accumulated in HISN3-overexpressing cells than in the wild type. In contrast, RNA interference of HISN3 depressed Ni accumulation but caused cellular sensitivity to Ni. The elevated metal absorption in the HISN3-overexpressing algae implies that the metals can be removed from water media. Thus, our work presents an example for algae genetically designed to improve tolerance to metal toxicity and environmental restoration of metal-contaminated aquatic ecosystems.

[Levels of blood pressure and blood glucose in elderly patients with hypertension and diabetes: association with carotid atherosclerosis].

OBJECTIVE: To explore the association between blood pressure and blood glucose levels and carotid atherosclerosis in elderly patients with essential hypertension and type 2 diabetes mellitus (T2DM). METHODS: A total of 670 patients aged 60 years or over with hypertension and T2DM were recruited and categorized by their systolic blood pressure (SBP): tight control, < 130 mm Hg, usual control, 130 - 139 mm Hg, or uncontrolled, ≥ 140 mm Hg; and by their HbA1c level: tight control < 6.5%, usual control 6.5% - 7.5%, or uncontrolled, ≥ 7.5% respectively. Carotid ultrasonography was performed in all subjects for the evaluations of intima-media thickness (IMT) and plaque. RESULTS: Multiple linear regression analyses revealed that IMT was positively correlated with SBP (ß = 0.215, P = 0.002) and HbA1c (ß = 0.149, P = 0.031), whereas IMT was negatively correlated with high-density lipoprotein cholesterol (ß = -0.196, P = 0.002). According to the multivariate logistic regression analysis, SBP ≥ 140 mm Hg (OR = 1.473, 95%CI 1.044 - 2.078 P = 0.027), HbA1c ≥ 7.5% (OR = 1.445, 95%CI 1.031 - 2.027, P = 0.033) and total cholesterol (OR = 1.014, 95%CI 1.004 - 1.024, P = 0.019) were significant risk factors for carotid artery atherosclerotic plaques whereas high-density lipoprotein cholesterol (OR = 0.895, 95%CI 0.805 - 0.994, P = 0.012) was a protective factor for carotid artery atherosclerotic plaques in elderly patients with hypertension and T2DM. CONCLUSION: There is a significant correlation between the levels of blood pressure, blood glucose and carotid atherosclerosis in elderly patients.