Organoids in modelling infectious diseases

Approaches based on animal and two-dimensional (2D) cell culture models cannot ensure reliable results in modeling novel pathogens or in drug testing in the short term; therefore, there is rising interest in platforms such as organoids. To develop a toolbox that can be used successfully to overcome current issues in modeling various infections, it is essential to provide a framework of recent achievements in applying organoids. Organoids have been used to study viruses, bacteria, and protists that cause, for example, respiratory, gastrointestinal, and liver diseases. Their future as models of infection will be associated with improvements in system complexity, including abilities to model tissue structure, a dynamic microenvironment, and coinfection.Teaser.Organoids are a flexible tool for modelling viral, bacterial and protist infections. They can provide fast and reliable information on the biology of pathogens and in drug screening, and thus have become essential in combatting emerging infectious diseases.     

Heparanase-1 is downregulated in chemoradiotherapy orbital rhabdomyosarcoma and relates with tumor growth as well as angiogenesis

AIM:To determine the role of heparanase-1(HPSE-1)in orbital rhabdomyosarcoma(RMS),and to investigate the feasibility of HPSE-1 targeted therapy for RMS.METHODS:Immunohistochemistry was performed to analyze HPSE-1 expression in 51 cases of orbital RMS patients(including 28 cases of embryonal RMS and 23 cases of alveolar RMS),among whom there were 27 treated and 24 untreated with preoperative chemoradiotherapy.In vitro,studies were conducted to examine the effect of HPSE-1 silencing on RMS cell proliferation and tube formation of human umbilical vein endothelial cells(HUVECs).RD cells(an RMS cell line)and HUVECs were infected with HPSE-1 sh RNA lentivirus at a multiplicity of infection(MOI)of 10 and 30 separately.Real-time PCR and Western blot were applied to detect the m RNA and protein expression levels of HPSE-1.Cell viability of treated or control RD cells was evaluated by cell counting kit-8(CCK-8)assay.Matrigel tube formation assay was used to evaluate the effect of HPSE-1 RNAi on the tube formation of HUVECs.RESULTS:Immunohistochemistry showed that the expression rate of HPSE-1 protein was 92.9%in orbital embr yonal RMS and 91.3%in orbital alveolar RMS.Tissue from alveolar orbital RMS did not show relatively stronger staining than that from the embryonal orbital RMS.However,despite the types of RMS,comparing the cases treated chemoradiotherapy with those untreated,we have observed that chemoradiotherapy resulted in weaker staining in patients’tissues.The expression levels of HPSE-1 declined significantly in both the m RNA and protein levels in HPSE-1 sh RNA transfected RD cells.The CCK-8 assay showed that lentivirus-mediated HPSE-1 silencing resulted in significantly reduced RD cells viability in vitro.Silencing HPSE-1 expression also inhibited VEGF-induced tube formation of HUVECs in Matrigel.CONCLUSION:HPSE-1 silencing may be a promising therapy for the inhibition of orbital RMS progression.     

2015—2019年某焦化厂下风向居民血清免疫球蛋白分析

目的： 比较2015—2019年某焦化厂下风向居民不同人群血清免疫球蛋白的含量并分析其变化趋势。方法： 2015—2019年夏季，选取中国北部某焦化厂下风向（1~2 km）两个村庄的常住居民为研究群体，按照一定的纳入排除标准确定研究对象，采集其血液及尿液通过全自动生化分析仪分别检测血清免疫球蛋白（IgG、IgA和IgM）含量及尿肌酐（Cr），并对血清免疫球蛋白含量异常率进行统计分析。尿液中多环芳烃代谢物1-羟基芘的含量采用高效液相色谱-荧光法检测。结果： 2015—2019年某焦化厂下风向居民中，女性血清IgG含量均值在各年份间均高于男性（P<0.01），IgM含量均值在2015年和2016年高于男性（P<0.05）；成人血清IgG和IgA含量均值在各年份间均高于未成年人（P<0.01），IgM含量均值在2016年低于未成年人（P<0.01）。2015—2019年某焦化厂下风向居民血清免疫球蛋白含量异常率总体呈先上升后下降的趋势，血清IgA和IgM在不同年份间的差异具有统计学意义（P<0.01），且2016年成人血清IgG、IgA和IgM含量异常率均高于未成年人（P<0.05），2015年和2016年女性血清IgG含量异常率高于男性（P<0.05）。2015—2019年，该地区居民尿液中多环芳烃代谢产物1-羟基芘的检出水平（用尿肌酐含量校正）中位数依次为0.468、0.797、0.678、0.169和0.021 μg/g。结论： 2015—2019年焦化厂下风向居民血清免疫球蛋白（IgG、IgA和IgM）含量具有一定的性别差异和年龄差异，其异常率总体呈现先上升后下降的趋势。     

β-arrestin1在炎-癌转化中的研究进展

β-arrestin1(ARRB1)作为β-arrestin（ARRB）家族成员，是一类具有多种生物学功能的细胞内支架蛋白。其参与调控G蛋白偶联受体（G protein-coupled receptor，GPCR）和非GPCR介导的信号通路。ARRB1与炎症和癌症密切相关，不仅参与炎症形成，而且通过多种方式调节炎癌转化的进程。因此对ARRB1的生物学特性及其在炎癌转化中作用的研究，将有助于揭示其对人类肿瘤进程干预的潜在价值。     

Evaluation of the effects of temporomandibular joint arthrocentesis with hyaluronic acid injection on mandibular condyles using fractal dimension analysis: A retrospective study

This study aimed to investigate the effects of arthrocentesis with intra-articular hyaluronic acid (HA) injection on mandibular condyles using fractal dimension (FD) analysis.Patients with temporomandibular joint (TMJ) internal derangement (ID) were divided into three groups according to how many times the arthrocentesis with HA injection was performed. FD analysis is a quantitative concept that provides information about trabecular bone microstructures. Regions of interest were selected from bone areas close to the articular surfaces of the right and left condyles on panoramic radiographs, which were taken before the procedure (T0) and at the sixth month (T1) after the procedure. Then, the FD values were calculated. All images were reviewed by the same researcher. A two-way repeated-measures analysis of variance was used to determine whether there was a significant interaction between groups, treatment sides, and time on the FD values.A total of 140 patients, including 118 patients who received bilateral arthrocentesis with HA injection and 22 control patients, were included in the study. The images of 20 randomly selected patients were re-evaluated after 2 weeks. As a result of the correlation analysis, there was no significant difference between the two measurements (P > 0.05). The main effect of time on the FD value was significant [F (1, 136) = 157.879, P < 0.001]. This effect was qualified by a significant time × group interaction effect [F (3, 136) = 18.533, P < 0.001]. The increases in the mean FD values on the right and left sides in all treatment groups between T0 and T1 times were significant (P < 0.001 for all), whereas changes in FD values on the right and left sides between T0 and T1 times were not significant in the control group (P = 0.164 and P = 0.557, respectively). After arthrocentesis with HA injections, the mean FD values increased in the mandibular condyles, depending on time in all treatment groups.Patients with TMJ ID are likely to have radiologically detectable degenerative changes and abnormalities in the condyles. The FD analysis method, which provides quantitative data, is recommended as an adjunct and guide for oral and maxillofacial surgeons in radiological examinations that should be performed together with clinical examination for the follow-up of microstructural changes in the condyle after arthrocentesis with HA injection.     

Cortical mechanisms underlying variability in intermittent theta-burst stimulation-induced plasticity: A TMS-EEG study

ObjectiveTo test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).MethodsIn a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.ResultsThe facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.ConclusionsThe results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.SignificanceThese observations can be used to optimize iTBS investigational and therapeutic applications.     

Functional outcomes and complications after treatment of distal radius fracture in patients sixty years and over: A systematic review and network meta-analysis

AimThis network meta-analysis aims to compare functional outcomes and complications between conservative treatment and surgery for distal radius fractures in patients aged 60 years and over.MethodsWe searched the PubMed, EMBASE, and Web of Science databases for randomized controlled trials (RCTs) assessing the effect of conservative treatment and surgery for distal radius fractures in patients aged 60 years and over. Primary outcomes included grip strength and overall complications. Secondary outcomes included Disabilities of the Arm, Shoulder, and Hand (DASH) scores, Patient-Rated Wrist Evaluation (PRWE) scores, wrist range of motion and forearm rotation, and radiographic assessment. All continuous outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs), and binary outcomes were assessed using odds ratio (OR) with 95% CIs. The surface under the cumulative ranking curve (SUCRA) was used to determine a hierarchy of treatments. Cluster analysis was performed for grouping treatments based on the SUCRA values of primary outcomes.ResultsFourteen RCTs were included to compare conservative treatment, volar lockedplate (VLP), K-wires fixation, and external-fixation. VLP outperformed conservative treatment for 1-year and minimum 2-year grip strength (SMD; 0.28 [0.07 to 0.48] and 0.27 [0.02 to 0.53], respectively). VLP yielded the optimal grip strength at 1-year and minimum 2-year follow-up (SUCRA; 89.8% and 86.7%, respectively). In a subgroup analysis of patients aged 60 to 80 years old, VLP outperformed conservative treatment in DASH and PRWE scores (SMD, 0.33 [0.10, 0.56] and 0.23 [0.01, 0.45], respectively). In addition, VLP had the fewest complications (SUCRA = 84.3%). Cluster analysis suggested that VLP and K-wire fixation were more effective treatment groups.ConclusionEvidence to date demonstrates that VLP provides measurable benefits in grip strength and fewer complications to those 60 years of age and over, and that benefit is not reflected in current practice guidelines. There is a subgroup of patients where K-wire fixation outcomes are similar to those of VLP; defining this subgroup may yield substantial societal benefits.     

Nutraceuticals use and type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM.