Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Aim:

Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.

Methods:

Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg⁻¹·d⁻¹) or PEG-CDs (size: 8.3 nm, 5 mg·kg⁻¹·d⁻¹) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos'' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf.

Results:

Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments.

Conclusion:

CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.     

Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study

Aim:

To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women.

Methods:

A total of 485 healthy postmenopausal Chinese women (63.44±5.04 years) were enrolled in this open-label, 2-year, prospective, community-based trial. The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 μg/d), respectively, for 2 years. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, β-CTX and P1NP were measured, and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups.

Results:

Four hundred and sixty one participants completed this study. Serum levels of 25-hydroxyvitamin D were significantly increased in group C, but not changed in groups A and B at 24-month follow-up. Serum levels of parathyroid hormone, bone turnover marker β-CTX and bone formation marker P1NP were significantly decreased in group C, while serum levels of β-CTX were increased in group A at 24-month follow-up. The participants in group C maintained the grip strength, while those in groups A and B exhibited decreased grip strength at 24-month follow-up. The quality of life for the participants in groups B and C remained consistent, but that in group A was deteriorated at 24-month follow-up.

Conclusion:

Supplementation with calcitriol and calcium modifies the bone turnover marker levels, and maintains muscle strength and quality of life in postmenopausal Chinese women, whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life.     

High Diagnostic Accuracy and Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Malignant Lymph Nodes: A Systematic Review and Meta-Analysis

Digestive Diseases and Sciences - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is increasingly being used for diagnosing lymphadenopathy. We aim to systematically review the...     

The therapeutic effect and safety of the drugs for COVID-19: A systematic review and meta-analysis

Background:Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial.Objective:This study aimed to evaluate the efficiency and safety of the COVID-19 medicine.Methods:Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events.Results:A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79–1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98–1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01–1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63–0.88, P < .05) of COVID-19 medicine is lower than control group.Conclusion:The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.     

The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A protocol for systematic review and meta-analysis

Background:Glucokinase activators are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus (T2DM). Glucokinase activators blind to GK activate the enzyme allosterically. Treatment with different GKAs has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes. We compared the efficacy/safety of glucokinase activators in T2DM patients through a meta-analysis.Methods:We searched PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. Two independent reviewers extracted the information from article. The quality of articles were assessed by 2 independent reviewers using the 5 items of scale proposed by Jadad. We computed the weighted mean difference and 95% confidence interval (CI) for a change from baseline to the study endpoint for glucokinase activators vs placebo. Egger test and Begg test were used to assess the possible publication bias caused by the tendency of published studies to be positive.Results:The present meta-analysis will compare the efficacy and safety of glucokinase activators and placebo for the treatment of T2DM.Conclusions:This meta-analysis will provide advanced evidence on the efficacy and safety of glucokinase activators for the treatment of T2DM.Ethics and dissemination:Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journalPROSPERO registration number:CRD42021220364.     

The necessity or not of the addition of fusion to decompression for lumbar degenerative spondylolisthesis patients: A PRISMA compliant meta-analysis

Background:The new emerging application of decompression combined with fusion comes with a concern of cost performance, however, it is a lack of big data support. We aimed to evaluate the necessity or not of the addition of fusion for decompression in patients with lumbar degenerative spondylolisthesis.Methods:Potential studies were selected from PubMed, Web of Science, and Cochrane Library, and gray relevant studies were manually searched. We set the searching time spanning from the creating date of electronic engines to August 2020. STATA version 11.0 was exerted to process the pooled data.Results:Six RCTs were included in this study. A total of 650 patients were divided into 275 in the decompression group and 375 in the fusion group. No statistic differences were found in the visual analog scales (VAS) score for low back pain (weighted mean difference [WMD], –0.045; 95% confidence interval [CI], –1.259–1.169; P = .942) and leg pain (WMD, 0.075; 95% CI, –1.201–1.35; P = .908), Oswestry Disability Index (ODI) score (WMD, 1.489; 95% CI, –7.232–10.211; P = .738), European Quality of Life-5 Dimensions (EQ-5D) score (WMD, 0.03; 95% CI, –0.05–0.12; P = .43), Odom classification (OR, 0.353; 95% CI 0.113–1.099; P = .072), postoperative complications (OR, 0.437; 95% CI, 0.065–2.949; P = .395), secondary operation (OR, 2.541; 95% CI 0.897–7.198; P = .079), and postoperative degenerative spondylolisthesis (OR = 8.59, P = .27). Subgroup analysis of VAS score on low back pain (OR = 0.77, 95% CI, 0.36–1.65; P = .50) was demonstrated as no significant difference as well.Conclusion:The overall efficacy of the decompression combined with fusion is not revealed to be superior to decompression alone. At the same time, more evidence-based performance is needed to supplement this opinion.     

Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients in Jingzhou,Hubei Province of China

To evaluate the clinical characteristics and liver injury in coronavirus disease 2019 (COVID-19) patients, and analyze the differences between suspected and confirmed COVID-19 patients, this retrospective study was performed on 157 COVID-19 patients and 93 suspected patients who were ultimately excluded from COVID-19 (control patients). Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients were analyzed. Age, male sex, fever, chest tightness and dyspnea were related to the severity of COVID-19. C-reactive protein (CRP) and D-dimer may be predictors of the severity of COVID-19. Computed tomography (CT) played an important role in the screening of COVID-19 and the evaluation of disease severity. Multiple factors may cause liver injury in COVID-19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be more likely to cause liver injury than common respiratory infectious diseases. Age, temperature (T), white blood cell (WBC), lymphocytes (LY), hematocrit (HCT), CRP, and finger pulse oxygen saturation (SpO₂₎ may correlate with liver function impairment and may predict the occurrence and severity of liver function impairment. Some therapeutic drugs (like glucocorticoid) may be involved in the liver function impairment of COVID-19 patients. Most liver function indices improved significantly after active treatment. Although COVID-19 and other common respiratory infectious diseases share some clinical characteristics, COVID-19 has its own characteristics.     

Porcine germline genome engineering

Germline editing, the process by which the genome of an individual is edited in such a way that the change is heritable, has been applied to a wide variety of animals [D. A. Sorrell, A. F. Kolb, Biotechnol. Adv. 23, 431–469 (2005); D. Baltimore et al., Science 348, 36–38 (2015)]. Because of its relevancy in agricultural and biomedical research, the pig genome has been extensively modified using a multitude of technologies [K. Lee, K. Farrell, K. Uh, Reprod. Fertil. Dev. 32, 40–49 (2019); C. Proudfoot, S. Lillico, C. Tait-Burkard, Anim. Front. 9, 6–12 (2019)]. In this perspective, we will focus on using pigs as the model system to review the current methodologies, applications, and challenges of mammalian germline genome editing. We will also discuss the broad implications of animal germline editing and its clinical potential.     

Orexin A Suppresses the Expression of Exosomal PD-L1 in Colon Cancer and Promotes T Cell Activity by Inhibiting JAK2/STAT3 Signaling Pathway

Digestive Diseases and Sciences - Colon cancer, ranked third in cancer related mortality, is the most common malignant cancer of digestive tract. Though immune checkpoint inhibitors show promising...