Programmed cell death protein 1 and vitiligo Lin, Xiran; Meng, Xianmin; Song, Zhiqi
International journal of dermatology,
September 2019, Letnik:
58, Številka:
9
Journal Article
This paper aimed to study the adoption of deep learning (DL) algorithm of oral lesions for segmentation of cone-beam computed tomography (CBCT) images. 90 patients with oral lesions were taken as ...research subjects, and they were grouped into blank, control, and experimental groups, whose images were treated by the manual segmentation method, threshold segmentation algorithm, and full convolutional neural network (FCNN) DL algorithm, respectively. Then, effects of different methods on oral lesion CBCT image recognition and segmentation were analyzed. The results showed that there was no substantial difference in the number of patients with different types of oral lesions among three groups (P>0.05). The accuracy of lesion segmentation in the experimental group was as high as 98.3%, while those of the blank group and control group were 78.4% and 62.1%, respectively. The accuracy of segmentation of CBCT images in the blank group and control group was considerably inferior to the experimental group (P<0.05). The segmentation effect on the lesion and the lesion model in the experimental group and control group was evidently superior to the blank group (P<0.05). In short, the image segmentation accuracy of the FCNN DL method was better than the traditional manual segmentation and threshold segmentation algorithms. Applying the DL segmentation algorithm to CBCT images of oral lesions can accurately identify and segment the lesions.
Autosomal-dominant congenital stromal corneal dystrophy (CSCD) is a human genetic disease characterized by corneal opacities beginning shortly after birth. It is linked to a frameshift mutation in ...decorin, resulting in a C-terminal truncation lacking 33 amino acids that includes the “ear” repeat, a feature specific for small leucine-rich proteoglycans. Our goals are to elucidate the roles of the mutant decorin in CSCD pathophysiology and to decipher the mechanism whereby mutant decorin affects matrix assembly. A novel animal model that recapitulates human CSCD was generated. This transgenic mouse model targets expression of truncated decorin to keratocytes, thereby mimicking the human frameshift mutation. Mutant mice expressed both wild-type and mutant decorin. Corneal opacities were found throughout, with increased severity toward the posterior stroma. The architecture of the lamellae was disrupted with relatively normal lamellae separated by regions of abnormal fibril organization. Within abnormal zones, the interfibrillar spacing and the fibril diameters were increased. Truncated decorin negatively affected the expression of endogenous decorin, biglycan, lumican, and keratocan and positively affected fibromodulin. Our results provide a mechanistic explanation for the generation of corneal opacities in CSCD. Thus, truncated decorin acts in a dominant-negative manner to interfere dually with matrix assembly and binding to receptor tyrosine kinases, thereby causing abnormal expression of endogenous small leucine-rich proteoglycans leading to structural abnormalities within the cornea and vision loss.
The Chinese Space Station Optical Survey (CSS-OS) is a mission to explore the vast universe. This mission will equip a 2-meter space telescope to perform a multi-band NUV-optical large area survey ...(over 40
%
of the sky) and deep survey (
∼
1
%
of the sky) for the cosmological and astronomical goals. Galaxy detection is one of the most important methods to achieve scientific goals. In this paper, we evaluate the galaxy number density for CSS-OS in i band (depth, i ∼ 26 for large area survey and ∼27 for the deep survey, point source, 5
σ
) by the method of image simulation. We also compare galaxies detected by CSS-OS with that of LSST (i ∼ 27, point source, 5
σ
). In our simulation, the HUDF galaxy catalogs are used to create mock images due to long enough integration time which meets the completeness requirements of the galaxy analysis for CSS-OS and LSST. The galaxy surface profile and spectrum are produced by the morphological information, photometric redshift and SEDs from the catalogs. The instrumental features and the environmental condition are also considered to produce the mock galaxy images. The galaxies of CSS-OS and LSST are both extracted by SExtractor from the mock i band image and matched with the original catalog. Through the analysis of the extracted galaxies, we find that the effective galaxy number count is
∼
13
arcmin
−
2
,
∼
40
arcmin
−
2
and
∼
42
arcmin
−
2
for CSS-OS large area survey, CSS-OS deep survey and LSST, respectively. Moreover, CSS-OS shows the advantage in small galaxy detection with high spatial resolution, especially for the deep survey: about 20
%
of the galaxies detected by CSS-OS deep survey are not detected by LSST, and they have a small effective radius of
r
e
<
0.3
″
.
Primary malignant mesothelioma (MM) of spermatic cord is extremely rare. We presented two malignant mesotheliomas involving the spermatic cords; one was primary, one secondary. The secondary one ...represented the direct involvement by a peritoneal MM. No occupational exposure to asbestos was identified in either patient. Both of them presented with a painless inguinal mass. Microscopically the primary MM was epithelioid type with tumor nests infiltrating adjacent adipose tissue, while the secondary MM grew in mixed type. No tumor necrosis was seen in the primary MM, while extensive necrosis was seen in the secondary one. Rare mitotic figure was seen in the primary MM while the mitosis in the secondary tumor was brisk, and with atypical mitosis. Immunohistochemically the tumor cells were positive for calretinin and CK5/6 and negative for BER-EP4 and BRST3 in both cases. The reported cases of primary MM from spermatic cord in English literature were briefly reviewed.
Tuberculosis (TB) is the leading opportunistic infection of people living with human immunodeficiency virus (HIV; PLWH). Cytochrome P450 (CYP) 2B6 and ATP-binding cassette sub-family B member 1 (
) ...are involved in the metabolism and transportation of efavirenz. The study was aimed to investigate the effects of rifampicin,
and
polymorphisms on efavirenz exposure in Chinese PLWH co-infected with TB.
PLWH were screened according to inclusion and exclusion criteria and divided into HIV group and HIV/TB group. Efavirenz plasma concentration (C
) was determined, dose-adjusted concentration (C
/D) was calculated, and genotypes of
516G>T, 785A>G, and
2677G>T, 3435C>T were analyzed.
252 PLWH were enrolled, including 75 co-infected with TB and concomitant with rifampicin. Efavirenz C
and C
/D were both higher in HIV group (1.94 μg/mL, 0.2007 (μg/ml)/(mg/kg/d)) compared with HIV/TB group (1.52 μg/mL, 0.1557 (μg/ml)/(mg/kg/d)) (
= .001). Efavirenz C
/D was significantly higher in patients with variant genotypes of
516G>T and 785A>G (
<.001), and was significantly lower in HIV/TB group compared with HIV group among patients with
516 GG, TT, and 785 AA, AG genotypes (
< .05).
Efavirenz exposure is reduced by co-administration with rifampicin, and related to genetic polymorphisms of
Doxorubicin (DOX) has a cytotoxic effect on many tumor cells; however, its clinical application is limited owing to its strong side effects. Although Doxil® reduces the cardiotoxicity of free DOX, it ...has also introduced a new dose-limiting toxicity. In a previous study, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified onto the surface of DOX-loaded liposomes to target tumor-associated macrophages (TAMs), further improving the efficacy of DOX-loaded liposomes over that of Doxil®. Meanwhile, the good retention characteristics and promising antitumor ability of sphingomyelin/cholesterol (SM/CH) system for water-soluble drugs have attracted wide attention. Therefore, we aimed to use SA-CH as the target and hydrogenated soybean phosphatidylcholine (HSPC) or egg sphingomyelin (ESM) as the membrane material to develop a more stable DOX-loaded liposome with stronger antitumor activity. The liposomes were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency,
in vitro
release, long-term storage, cytotoxicity, cellular uptake, pharmacokinetics, tumor targetability, and
in vivo
antitumor activity. In the liposomes prepared using HSPC/CH, sialic acid (SA) modification considerably increased the accumulation of DOX-loaded liposomes in the tumor, thus exerting a better antitumor effect. However, SA modification in DOX-ESL (SA-CH-modified DOX-loaded liposomes prepared by ESM/CH) destroyed the strong retention effect of the ESM/CH system on DOX, resulting in a reduced antitumor effect. Notably, DOX-ECL (DOX-loaded liposome prepared by ESM/CH) had the optimal storage stability, lowest toxicity, and optimal antitumor effect due to better drug retention properties. Thus, the ESM/CH liposome of DOX is a potential drug delivery system.
Graphical Abstract
Sketch of the effect of two DOX-loaded liposomes with hydrogenated soybean phospholipid (HSPC) and egg sphingomyelin (ESM) as lipid membrane material and surface-modified SA derivative on tumor growth inhibition.
Traditional Chinese medicine Tongxinluo (TXL) has been widely used to treat coronary artery disease in China, since it could reduce myocardial infarct size and ischemia/reperfusion injury in both ...non-diabetic and diabetic conditions. It has been shown that TXL could regulate peroxisome proliferator activated receptor-α (PPAR-α), a positive modulator of angiopoietin-like 4 (Angptl4), in diabetic rats. Endothelial junction substructure components, such as VE-cadherin, are involved in the protection of reperfusion injury. Thus, we hypothesized cell-intrinsic and endothelial-specific Angptl4 mediated the protection of TXL on endothelial barrier under high glucose condition against ischemia/reperfusion-injury via PPAR-α pathway.
Incubated with high glucose medium, the human cardiac microvascular endothelial cells (HCMECs) were then exposed to oxygen-glucose-serum deprivation (2 hours) and restoration (2 hours) stimulation, with or without TXL, insulin, or rhAngptl4 pretreatment.
TXL, insulin, and rhAngptl4 had similar protective effects on the endothelial barrier. TXL treatment reversed the endothelial barrier breakdown in HCMECs significantly as identified by decreasing endothelial permeability, upregulating the expression of JAM-A, VE-cadherin, and integrin-α5 and increasing the membrane location of VE-cadherin and integrin-α5, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with small interfering RNA (siRNA) interference and PPAR-α inhibitor MK886 partially abrogated these beneficial effects of TXL. Western blotting also revealed that similar with insulin, TXL upregulated the expression of Angptl4 in HCMECs, which could be inhibited by Angptl4 siRNA or MK886 exposure. TXL treatment increased PPAR-α activity, which could be diminished by MK886 but not by Angptl4 siRNA.
These data suggest cell-intrinsic and endothelial-specific Angptl4 mediates the protection of TXL against endothelial barrier breakdown during oxygen-glucose-serum deprivation and restoration under high glucose condition partly via the PPAR-α/Angptl4 pathway.
PDF
