老年翼状胬肉患者翼状胬肉切除与角膜缘干细胞移植联合治疗的疗效观察

摘要 目的：分析评估老年翼状胬肉患者实施翼状胬肉切除与角膜缘干细胞移植联合治疗的临床效果。方法：回顾性纳入的本院2018年08月至2020年07月期间295例翼状胬肉患者（共442只眼）的临床资料,根据术式差异将患者分为联合组（150例,共224只眼）和参照组（145例,共218只眼）,参照组病患仅择取翼状胬肉切除手术,联合组病患于以上基础实施角膜缘干细胞移植术,比较两组病患术前及术后各时间点（1周、1个月、3个月）的BUT、SIt、UCVA、CAD、CAA,统计病患术后3个月的复发情况。结果：两组BUT在术后1周较术前显著缩短（P<0.05）,而在术后1月和3月较术前显著延长（P<0.05）,两组BUT在术后1周对比差别明显（P<0.05）,而其他时间点对比没有明显差别（P>0.05）。两组术前术后SIt对比没有明显差别（P>0.05）,术后1月和3月的两组UCVA均高于术前（P<0.05）,而两组在各时间点UCVA对比没有明显差别（P>0.05）,两组术后各时间点的角膜CAD较术前显著性降低（P<0.05）,而两组角膜CAD在各时间点无明显差别（P>0.05）。两组术后CAA术后3月与术前比较,WR比例显著降低,AR、OA比例显著增加（P<0.05）,而组间对比没有明显差别（P>0.05）。术后复发率联合组（6.67%）与参照组（32.26%）对比有明显差别（P<0.05）。结论：与翼状胬肉切除术比较 ,老年翼状胬肉病患实施翼状胬肉切除与角膜缘干细胞移植术联合治疗对患者早期眼表无较大影响,两种术式均不影响泪液分泌,且能够改善裸眼视力、散光度及轴向,但联合治疗在降低术后复发率方面优势明显。     

L’exploitation de la faune par les groupes humains du Pléniglaciaire supérieur à Eliseevichi 1 (Russie)

The archaeological site of Eliseevichi 1, located in the Dnieper River Basin, was discovered in 1930 by K.M. Polikarpovich. It is contemporary of Epigravettian occupations of the end of the second half of the upper Pleniglacial (20,000–14,000 years BP). As for the sites of the culture of Mezine (Mezine, Mezhirich, Gontsy and Dobranitchevka), it was interpreted as a specialized camp of hunters, mainly for slaughtering woolly mammoths and fur exploitation. Moreover, mammoth bones have been used to build larger structures than in mezinian sites associated with storage pits, as in Timonovka I, Yudinovo, Yourevitchi, Suponevo and Chulatovo. However, Eliseevichi 1 differs from all other sites by the presence of ivory engraved pieces with zigzag patterns and multiple linear features and the presence of platelets with decorations in the form of fish scales (“churingas”) and the high number of chisels. These features make it a unique case in the Desna Valley. To better understand the activities that have been implemented within the site by human groups, particularly the role of different species, we processed to the zooarchaeological study of the faunal remains from the 1935–1936 excavations. The faunal spectrum is restricted, typical of a cold and dry environment, with Mammuthus primigenius, Rangifer tarandus, Canis lupus, Alopex lagopus rossicus and Ursus arctos. Two skulls were previously identified as being those of dogs. According to the taphonomical study we highlighted a quick and deep burying of bones, which were affected by freeze-thaw alternating, without being highly altered and moved by phenomena of cryoturbation. The woolly mammoth was used for its meat and for its ivory. The many remains of canids are characterized by skinning marks and long bones were sawed. The presence of ocher, ashy areas, crude lithic fragments, could be linked to the treatment of skins. The site of Eliseevichi 1 was probably occupied during winter and summer seasons, several times during a long period. It could have two main functions, not as a habitat but as a specialized site of furskin and bone production.     

Immune checkpoint blockade and its combination therapy with small-molecule inhibitors for cancer treatment

Initially understood for its physiological maintenance of self-tolerance, the immune checkpoint molecule has recently been recognized as a promising anti-cancer target. There has been considerable interest in the biology and the action mechanism of the immune checkpoint therapy, and their incorporation with other therapeutic regimens. Recently the small-molecule inhibitor (SMI) has been identified as an attractive combination partner for immune checkpoint inhibitors (ICIs) and is becoming a novel direction for the field of combination drug design. In this review, we provide a systematic discussion of the biology and function of major immune checkpoint molecules, and their interactions with corresponding targeting agents. With both preclinical studies and clinical trials, we especially highlight the ICI + SMI combination, with its recent advances as well as its application challenges.     

The effects of microRNAs in activating neovascularization pathways in diabetic retinopathy

Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus that causes diabetic macular edema and visual loss. DR is categorized, based on the presence of vascular lesions and neovascularization, into non-proliferative and proliferative DR. Vascular changes in DR correlate with the cellular damage and pathological changes in the capillaries of blood-retinal barrier. Several cytokines have been involved in inducing neovascularization. These cytokines activate different signaling pathways which are mainly responsible for the complications of DR. Recently; microRNAs (miRNAs) have been introduced as the key factors in the regulation of the cytokine expression which plays a critical role in neovascularization of retinal cells. Some studies have demonstrated that changing levels of miRNAs have essential role in the pathophysiology of vascular changes in patients with DR. The aim of this study is to identify the effects of miRNAs in the pathogenesis of DR via activating neovascularization pathways.     

Biased T-cell receptor usage is associated with allelic variation in the MHC class II peptide binding groove

 A comprehensive analysis was carried out of the tri-molecular complex of peptide, major histocompatibility class II molecule, and T-cell receptor (TcR) involved in the recognition of the promiscuous HA (306–318) peptide, restricted by one of two closely related HLA-DR alleles, HLA-DRB1*0101 and HLA-DRB1*0103. These two DR molecules differ by only three amino acids at positions 67, 70, and 71, in the third variable region of the DRB1 chain. None of the HA (306–318)-specific T-cell clones restricted by these two DR molecules tolerated amino acid substitution at the peptide-binding position 71, despite the fact that the substitution did not interfere with peptide binding. The majority of the DRB1*0103-restricted clones tolerated substitution of the amino acid at the TcR-contacting position 70, while the DRB1*0101-restricted T cells did not. Biased usage of TRVA and TRVB segments was observed for the DRB1*0103-restricted clones; in contrast, apparently random usage was seen in the DRB1*0101-restricted T cells. Finally, limiting dilution analysis revealed a lower frequency of T cells reactive with the HA peptide in a DRB1*0103 compared with a DRB1*0101 individual. Taken together these data suggest that biased TcR gene usage may reflect a relatively low precursor frequency of T cells, and the need for clonal expansion of a limited set of high avidity T cells. Received: 7 August 1998 / Revised: 19 November 1998     

Numerical simulations of surface plasmon resonance system for monitoring DNA hybridization and detecting protein-lipid film interactions

This paper presents a simple method to extract information about thin organic films from surface plasmon resonance (SPR) spectra. From numerical simulations it was found that a shift (Δθ _SPR) of an absorption peak in the SPR spectrum was directly proportional to the product of the thin organic film thickness and the refractive index difference between the thin organic film and a buffer soaking the sample. It was also found that Δθ _SPR was not sensitive to the thin organic film support of a gold film and a glass cover slip. Relationships between Δθ _SPR and distributions of macromolecule structures, in the thin organic films were theoretically established. Formulae were derived for a homemade SPR system to calculate length, transverse area, density and surface concentration of macromolecules in the thin organic film. The validity of these treatments was checked by precisely measuring the size of a single distearoylphosphatidylcholine molecule on a gold-supported phospholipid film; by quantitatively monitoring hybridization of synthesized oligonucleotides strands based on a biotin/avidin system; and by quantitatively detecting the steric hindrance of rabbit C-reactive protein specifically bound to phospholipid monolayers composed of synthesized lipids. Received: 4 May 1998 / Revised version: 27 July 1998 / Accepted: 27 August 1998     

Immigration and emigration of Burkholderia cepacia and Pseudomonas aeruginosa between and within mixed biofilm communities

AIMS: To investigate the dynamics of binary culture biofilm formation through use of both the Sorbarod model of biofilm growth and the constant depth film fermenter (CDFF). METHODS AND RESULTS: Pseudo steady-state biofilm cultures of laboratory and clinical strains of Pseudomonas aeruginosa, selected on the basis of their ability to produce a Burkholderia cepacia growth-inhibitory substance, were established on Sorbarod filters and challenged with corresponding planktonic grown cultures of B. cepacia. Reverse challenges were also conducted. Both B. cepacia and P. aeruginosa were able to form steady-state monoculture biofilms after 48 h growth. When steady-state biofilms of B. cepacia NTCT 10661 were challenged with planktonically grown P. aeruginosa PAO1 known to produce a B. cepacia growth-inhibitory substance, the immigrant population was rapidly and almost completely bound to the biofilm, displacing B. cepacia. By contrast, established biofilms of P. aeruginosa PAO1 resisted immigration of B. cepacia 10661. Similar experiments conducted with a nongrowth inhibitory substance producing clinical pairing of P. aeruginosa 313113 and B. cepacia 313113 led to the formation of stable, mixed biofilm populations in both instances. Moreover, co-inoculation with these clinical isolates resulted in a stable, mixed steady-state biofilm. Similar observations were made for biofilms generated in CDFFs. In such instances following pan-swapping between two monoculture CDFFs, B. cepacia 313113 was able to integrate into an established P. aeruginosa 313113 biofilm to form a stable binary biofilm. CONCLUSIONS: Establishment of a mixed species community follows a specific sequence of inoculation that may either be due to some degree of match between co-colonizers or that P. aeruginosa predisposes uncolonized sections of the surface to permit B. cepacia colonization. SIGNIFICANCE AND IMPACT OF THE STUDY: Colonization of a surface with one bacterial species confers colonization resistance towards other species. Disinfection of a surface might well increase the probability of pathogen harbourage.     

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel “magnet probe test”. Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.5% tetracycline HCl, as a fluorescent marker, and were compressed using a Carver press. Tablets were coated with a solution consisting of 7% hydroxypropyl methylcellulose (HPMC) phthalate (HP-55), and 0.5% cetyl alcohl in acetone and isopropanol (11:9). The nature of polymer interaction with the tablets and coating was evaluated using CLSM and a designed magnet probe test. CLSM images clearly showed coating efficiency, thickness, and uniformity of film formation, and the extent of drug migration into the film at the coating interfaces of tablets. Among the excipients, MCC demonstrated the best interface for both film formation and uniformity in thickness relative to lactose monohydrate and dibasic calcium phosphate dihydrate. The detachment force of the coating layers from the tablet surfaces, as measured with the developed magnet probe test, was in the order of MCC>lactose monohydrate>dibasic calcium phosphate dihydrate. It was also shown that the designed magnet probe test provides reliable and reproducible results when used for measurement of film adhesion and bonding strength.