Effect of therapy with blood component (activated autoplasma) on blood glutathione level in patients with vascular abnormalities on the fundus oculi

Thirty-three patients with central chorioretinal dystrophy, 18 with proliferative diabetic retinopathy, and 15 controls without ocular diseases were examined. All patients were treated by blood components. The treatment started with activation of blood plasma platelets. Glutathione was measured in two portions of plasma: intact and containing platelet activation products. The content of glutathione was higher in activated autoplasma of 21 patients with central chorioretinal dystrophy and 6 patients with diabetic retinopathy than in intact plasma by 107 and 72%, respectively. A decrease in glutathione level in activated autoplasma was observed in 1 patient with central chorioretinal dystrophy and in 9 with diabetic retinopathy. Hence, antioxidant defense is decreased in diabetic retinopathy, since glutathione is involved in reduction of organic hydroperoxides.     

Potentialities of autofluorescent spectroscopy in diagnosis of laryngeal and pharyngeal tumors

Laryngeal and pharyngeal mucosa of 50 patients with malignant (n=56%) and benign (n=44%) laryngeal and pharyngeal tumors was examined with autofluorescent spectroscopy using nitrogen laser LGI-505 (337,1 nm). It was found that autofluorescent spectrum of malignant tumors is significantly less intensive than relevant spectrum of healthy mucosa and benign tumors.     

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis(ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However,whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3~(-/-) mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3~(-/-) mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water(AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch(alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3~(-/-) mice.Finally, AEW-induced astrocyte activation was inhibited in Cxcr3~(-/-)mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.     

加速康复外科对结直肠癌患者围术期炎症反应与免疫功能影响的Meta分析

目的:系统评价加速康复外科(ERAS)干预对结直肠癌择期手术患者围术期炎症反应与免疫功能的影响。方法:计算机检索多个国内外数据库中从建库至2018年发表的关于ERAS应用于结直肠癌手术的随机对照试验,检索时限均为从建库至2018年4月。按照Cochrane系统评价方法对纳入研究的进行质量评价和提取资料,采用Rev Man5.3软件进行Meta分析。结果:最终纳入26篇研究,共2420例患者,ERAS组1185例,对照组1235例。描述性分析结果显示,与对照组比较,ERAS组术后炎症因子水平明显降低,恢复时间明显缩短(均P0.05)。合并分析结果显示,ERAS组较对照组术后1、3、7d的CD4+T细胞百分比(WMD=0.85,95%CI=0.21~1.49;WMD=2.85,95%CI=1.76~3.94;WMD=1.52,95%CI=0.42~2.62)、Ig G水平(WMD=0.54,95%CI=0.11~0.97;WMD=1.26,95%CI=0.79~1.74;WMD=0.63,95%CI=0.27~0.99)明显升高,术后1、3d的CD3+T细胞百分比(WMD=1.46,95%CI=0.62~2.30;WMD=2.78,95%CI=1.82~3.73)、Ig A水平(WMD=0.14,95%CI=0.07~0.22;WMD=0.29,95%CI=0.22~0.36)明显升高,术后3d的Ig M水平(WMD=0.11,95%CI=0.06~0.16)明显升高(均P0.05),切口感染(OR=0.52,95%CI=0.31~0.85)、肺部感染(OR=0.40,95%CI=0.21~0.73)、泌尿系统感染(OR=0.15,95%CI=0.04~0.54)、术后肠梗阻(OR=0.34,95%CI=0.13~0.87)以及总并发症的发生率(OR=0.40,95%CI=0.28~0.56)均明显降低(均P0.05)。结论:ERAS可以安全应用于结直肠癌择期手术患者,能够降低结直肠癌患者围术期炎性介质的释放,维护机体的免疫稳定,从而减少并发症发生率,促进术后早期康复。     

机器人辅助和腹腔镜手术治疗直肠癌疗效与安全性比较的Meta分析

目的:系统评价机器人辅助直肠切除术(RP)与腹腔镜直肠切除术(LP)治疗直肠癌的疗效与安全性。方法:计算机检索多个国内外数据库,收集比较RP和LP治疗直肠癌的随机对照试验(RCT),检索时限均从建库至2018年3月28日。两名评价者严格按照纳入与排除标准筛选文献、提取资料,并进行文献质量评价,采用R 3.4.2软件进行Meta分析。结果:共纳入7个随机对照试验,共956例患者,其中RP组474例,LP组482例。Meta分析结果表明,与LP组比较,RP组的手术时间长(MD=28.88,95%CI=3.20～54.55,P=0.028)、中转开腹率低(RR=0.49,95%CI=0.31～0.78,P=0.003)、术后肠道功能恢复快(MD=-0.43,95%CI=-0.74～-0.13,P=0.006)、住院时间略短(MD=-0.95,95%CI=-1.84～-0.06,P=0.037)。在围手术期病死率、并发症发生率、近端及远端切缘距离、淋巴结清扫数目、术后开始流质饮食时间方面两组之间无统计学差异(均P0.05)。结论:RP的围手术期疗效优于LP;目前的数据无法准确判断两者远期疗效的优劣,比较RP与LP的远期疗效,有待高质量的RCT长期随访并记录两组的远期结果。     

Temporal scaling in C. elegans larval development

It is essential that correct temporal order of cellular events is maintained during animal development. During postembryonic development, the rate of development depends on external conditions, such as food availability, diet, and temperature. How timing of cellular events is impacted when the rate of development is changed at the organism level is not known. We used a unique time-lapse microscopy approach to simultaneously measure timing of oscillatory gene expression, hypodermal stem cell divisions, and cuticle shedding in individual Caenorhabditis elegans larvae, as they developed from hatching to adulthood. This revealed strong variability in timing between isogenic individuals under the same conditions. However, this variability obeyed “temporal scaling,” meaning that events occurred at the same time when measured relative to the total duration of development in each individual. We also observed pervasive changes in timing when temperature, diet, or genotype were varied, but with larval development divided in “epochs” that differed in how event timing was impacted. Yet, these variations in timing were still explained by temporal scaling when time was rescaled by the duration of the respective epochs in each individual. Surprisingly, timing obeyed temporal scaling even in mutants lacking lin-42/Period, presumed a core regulator of timing of larval development, that exhibited strongly delayed, heterogeneous timing. However, shifting conditions middevelopment perturbed temporal scaling and changed event order in a highly condition-specific manner, indicating that a complex machinery is responsible for temporal scaling under constant conditions.

Numerous cellular events that occur during animal development, such as cell division, cell movement, and gene expression, must be tightly coordinated in time to allow formation of a functional organism with a correctly established body plan. However, despite our increasing understanding of the regulation of developmental timing (1–3), how cells in developing organisms measure time and execute events in the correct temporal order remains poorly understood. Moreover, the rate of postembryonic development in animals is affected by external conditions, such as food availability, diet, and temperature. For example, severe dietary restriction extends the duration of larval development in the nematode worm Caenorhabditis elegans as much as tenfold, without apparent defects in development (4). How the timing of individual developmental events is adjusted in response to such changes in the organism-level rate of development is not known.This question about developmental timing has a parallel in the context of spatial patterning during development. It has been shown that spatial gene expression patterns often scale with organ or embryo size, that is, with the spatial pattern adjusted in each individual organ or embryo so that the spatial features occurred at the same position relative to its overall size (5–8). For example, in Drosophila embryos, gap genes are expressed in bands along the anteroposterior body axis (9, 10). These bands have highly stereotypical positions relative to the embryo’s size, even though this size shows significant variability between individuals (6). Moreover, embryos of closely related species that vary greatly in size exhibit the same number of bands with similar position relative to the size of the embryo (6). Here, we examine whether, analogous to scaling of spatial patterns in development, the timing of development exhibits temporal scaling, meaning that, when the organism-level rate of development is changed, the timing of individual events is adjusted so that they still occur at the same time, when measured relative to the total duration of development. Such a mechanism would ensure the correct synchrony of developmental events even when organism-level timing is changed in an unpredictable manner by shifts in external conditions.Due to its invariant cell lineage and highly stereotypical development, C. elegans is an ideal model for studying developmental timing. Its postembryonic development consists of four larval stages (L1 to L4) that are separated by a molting event, where a new cuticle is synthesized, and the old cuticle is shed (11). After the final L4 molt, animals enter adulthood. There is a clear periodic aspect to C. elegans development, with molts occurring every ~10 h at 25 °C. Moreover, larval stages are accompanied by oscillatory expression of ∼20% of genes, with peaks occurring once per larval stage (12–14).Molecular mechanisms that have been proposed for regulation of developmental timing include oscillators, that encode time in periodic changes in protein level, and “hourglass” mechanisms, that record time in the steady accumulation or degradation of proteins (15). Developmental timing has been extensively studied in C. elegans, leading to the discovery of heterochronic genes (2, 3). Heterochronic genes such as lin-14 and lin-28 show expression levels that decrease during larval development, suggestive of an hourglass mechanism (16, 17). Indeed, mutations that perturb the lin-14 and lin-28 temporal expression patterns lead to timing defects, with the identity of events in one larval stage switched with those of a later stage or repeated in subsequent stages (18). At the same time, these mutations otherwise have only limited impact on developmental timing on the organism level, for example, the duration of larval stages. In contrast, the heterochronic gene lin-42 is expressed in an oscillatory manner during development, peaking once every larval stage. In lin-42 mutants, developmental timing is severely perturbed, with strong animal-to-animal variability in larval stage duration (19). The body-wide, oscillatory expression dynamics of lin-42, together with its impact on larval stage duration, makes lin-42 an interesting candidate for a global regulator of developmental timing. Intriguingly, lin-42 is a homolog of Period, an important component of the circadian clock in Drosophila and higher organisms (20). Hence, it has been speculated that lin-42 forms part of an oscillator-based timer that allows cells and organs to read out developmental time (11).How timing of individual events is impacted by changes in the organism-level rate of development is poorly characterized. Timing of C. elegans larval development is often measured at the population level, by examining the developmental stage of animals sampled from age-synchronized populations. This approach has limited time resolution and does not allow measuring timing of multiple events within the same individual. The latter is a particular problem for mutants such as lin-42, where developmental synchrony between individual animals is lost. However, the alternative approach of following individual animals was, until recently, performed by hand, limiting the number of animals that could be examined. We have recently developed a microscopy approach that allows automated imaging of individual C. elegans larvae during their entire development and at single-cell resolution (21), making it possible to measure the timing of cellular events in many individual larvae. Here, we used this approach to simultaneously measure the timing of three recurring developmental events (oscillatory expression of a molting cycle gene, hypodermal stem cell divisions, and cuticle shedding) in individual C. elegans larvae, both upon changes in environmental conditions (temperature and diet) and in mutants that increased the duration of larval development up to threefold.Our measurements uncovered strong variability in event timing between individuals, as compared to duration of larval development, even in isogenic animals under identical environmental conditions. Strikingly, this variability obeyed temporal scaling, meaning that events occurred at the same time when rescaled by the total duration of development in each individual. Moreover, changes in average timing between populations that differ in genotype or environmental conditions were not always explained by a simple change in the overall rate of development of the organism. Instead, we found that larval development is divided into distinct epochs, which are sequences of events that, upon variation in conditions or genotype, exhibit changes in timing that are identical, and differ from changes in timing observed for events in other epochs. Yet, this variation in timing between populations also obeys temporal scaling, provided that event times were rescaled by the duration of individual epochs, rather than total duration of development. Surprisingly, we found this was even the case for lin-42 mutants, suggesting that, while lin-42 is crucial for setting the duration of larval stages, it is dispensable for controlling event timing relative to each larval stage. However, condition shifts during larval development perturbed temporal scaling and inverted event order, in a manner that depended on the type of shift. This hints that a complex machinery, potentially requiring coordination of different timing mechanisms, is responsible for temporal scaling under constant conditions.Overall, our results show that the broad variation observed between individuals, environmental conditions, and genotypes in the timing of cellular events during C. elegans postembryonic development can be captured by the simple concept of temporal scaling, thereby revealing a precise adaptation of cell-level timing to changes in the organism-level rate of development. These observations raise the important question of how temporal scaling is implemented by the molecular mechanisms that control timing of larval development.     

Comparative effectiveness of oral antibiotics,probiotics, prebiotics,and synbiotics in the prevention of postoperative infections in patients undergoing colorectal surgery: A network meta‐analysis

Oral antibiotics (OAB), probiotics, prebiotics, and synbiotics are reported to be effective for preventing postoperative infection following colorectal surgery, but the comparative effectiveness between them has not been studied. To compare these interventions through a network meta‐analysis. Ovid Medline, Embase, and the Cochrane Controlled Register of Trials (CENTRAL) were searched from inception to January 1, 2022 without any language restriction. Two reviewers independently screened the retrieved articles, assessed risk of bias, and extracted information from the included randomised controlled trials (RCTs). The primary outcome was infection rate, and the secondary outcome was anastomotic leakage rate. 4322 records were retrieved after literature search, and 20 RCTs recruiting 3726 participants were finally included. The analysis showed that usual care (UC) + Synbiotics ranked the most effective treatment (SUCRA = 0.968), UC + OAB ranked the second (SUCRA = 0.797), and UC + IAB ranked the third (SUCRA = 0.678) for preventing postoperative infection rate, but only UC + OAB achieved statistical significance. UC + OAB was the most effective treatment (SUCRA = 0.927) for preventing anastomotic leakage rate. Our study confirmed that preoperative administration of OAB was associated with lower infection rate and anastomotic leakage rate than placebo and UC alone. However, the beneficial effect of probiotics and synbiotics should still be investigated by large‐scale randomised controlled trials.