The effect and safety of atropine on delaying the progression of myopia has been extensively studied, but its optimal dose is still unclear. Therefore, the purpose of this meta-analysis is to ...systematically evaluate the safety and effectiveness of atropine in controlling the progression of myopia, and to explore the relationship between the dose of atropine and the effectiveness of controlling the progression of myopia.
This work was done through the data searched from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, a meta-analysis was performed using Revman5.3 software.
A total of 10 randomized controlled trials (RCTs) were included. Myopia progression was mitigated greater in the atropine treatment group than that in the control group, with MD = - 0.80, 95% CI (- 0.94, - 0.66) during the whole observation period. There was a statistical difference among 0.05, 0.5, and 1.0% atropine (P = 0.004). In addition, less axial elongation was shown, with MD = - 0.26, 95% CI (- 0.33, - 0.18) during the whole observation period.
The effectiveness of atropine in controlling the progression of myopia was dose related. A 0.05% atropine was likely to be the optimal dose.
The skin is an important protective barrier for human. The epithelial barrier is destroyed following a skin injury, thereby increasing the susceptibility of bacterial infections. After the skin is ...burned, the standard-of-care for burn wounds is minimizing trauma to the regenerating epidermis and dermis during gauze dressing changes. However, the use of conventional dressings for deep partial- and full-thickness burns always heal slowly. There are several wound dressings currently on the market that are used to cover the wound skin and promote healing. Peptide hydrogels show several beneficial properties. FEFEFKFK (F is phenylalanyl, K is lysinyl and E is glutamyl) can self-assemble to form a self-assembled peptide hydrogel (SAPH) with a nanofiber structure and has great potential in regenerative medicine. The FEFEFKFK-based SAPH (F-SAPH) was explored to be used as a wound dressing. First, there was no difference in the oxygen permeability and moisture permeability detected between F-SAPH and commercially available Comfeel®. In vitro data indicated good biocompatibility of F-SAPH. F-SAPH did not affect cell proliferation and differentiation, nor did it cause inflammatory reaction. In scald models without application of drugs, exogenous cytokines, or cells, F-SAPH reduced the inflammatory reaction, accelerated collagen deposition and epidermal regeneration, thereby promoting wound healing. In summary, F-SAPH acted as an excellent carrier for cell growth through biological simulation of extracellular matrix and retains various beneficial components secreted by cells, thereby contributing to the repair of damaged skin.
Alternative polyadenylation (APA) is emerging as a major post-transcriptional mechanism for gene regulation, and dysregulation of APA contributes to several human diseases. However, the functional ...consequences of APA in human cancer are not fully understood. Particularly, there is no large-scale analysis in cancer cell lines.
We characterized the global APA profiles of 6398 patient samples across 17 cancer types from The Cancer Genome Atlas and 739 cancer cell lines from the Cancer Cell Line Encyclopedia. We built a linear regression model to explore the correlation between APA factors and APA events across different cancer types. We used Spearman correlation to assess the effects of APA events on drug sensitivity and the Wilcoxon rank-sum test or Cox proportional hazards model to identify clinically relevant APA events.
We revealed a striking global 3'UTR shortening in cancer cell lines compared with tumor samples. Our analysis further suggested PABPN1 as the master regulator in regulating APA profile across different cancer types. Furthermore, we showed that APA events could affect drug sensitivity, especially of drugs targeting chromatin modifiers. Finally, we identified 1971 clinically relevant APA events, as well as alterations of APA in clinically actionable genes, suggesting that analysis of the complexity of APA profiles could have clinical utility.
Our study highlights important roles for APA in human cancer, including reshaping cellular pathways and regulating specific gene expression, exemplifying the complex interplay between APA and other biological processes and yielding new insights into the action mechanism of cancer drugs.
Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents ...may exhibit non-monotonic patterns in their dose–response relationships. Using a trial with two biological agents as an example, we propose a dose finding design to identify the biologically optimal dose combination, which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change point model is used to reflect the fact that the dose–toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose–efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the design proposed has desirable operating characteristics in identifying the biologically optimal dose combination under various patterns of dose–toxicity and dose–efficacy relationships.
To describe the clinical characteristics and the outcomes of strabismus surgery for acute acquired comitant esotropia (AACE).
Medical records of 45 AACE patients were retrospectively analyzed. The ...insertion location of medial rectus was compared between the AACE patients and comitant exotropic patients. The location was also compared with those measured in other studies. Surgical outcome measurements included amount of deviation and level of binocularity at last follow-up.
The distance from medial rectus to limbus was shorter in AACE patients than in patients with comitant exotropia. The distance was also shorter in AACE patients than patients in other studies. Out of the 45 patients, 2 had neurological diseases. Neostigmine test was negative in all patients. The age at onset of AACE was 5-47 years (mean 19.1 ± 7.3 years), one patient was 5 years (2.2%), 20 patients were 11-17 years (44.5%) and the other 24 patients were 18-47 years old (53.3%). The mean cycloplegic refraction was - 4.1 ± 3.0 diopters (D) and 41 patients were myopic (91%). The angle of deviation was 40.5 ± 19.5 prism diopters (PD) at distance and 35.6 ± 19.9PD at near preoperatively. The angle was 0.8 ± 1.6 PD at distance and 0.7 ± 1.8 PD at near postoperatively. Diplopia resolved in patients who underwent strabismus surgery, with no recurrence during the follow-up period. Thirty patients had stereopsis postoperatively.
AACE seems to occur mostly in older children and adults and myopes. The distance from the insertion to limbus of medial rectus was shorter in patients with AACE. Good results can be achieved by strabismus surgery.
Preeclampsia is associated with the insufficient invasion of trophoblasts. NF-κB is a transcription factor in almost all mammalian cells and has been validated to be upregulated in the maternal ...circulation and placenta of women with preeclampsia. MiR-518a-5p is also overexpressed in pre-eclamptic placenta. The present study was designed to explore whether NF-κB can transcriptionally activate miR-518a-5p and investigate the influences of miR-518a-5p on the viability, apoptosis, migration, and invasion of HTR8/SVneo trophoblast. In situ hybridization and real time polymerase chain reaction were used to reveal miR-518a-5p expression in placenta tissues and HTR8/SVneo cells, respectively. Cell migration and invasion were detected using Transwell inserts. Our findings indicated that NF-κB p52, p50, and p65 can bind to miR-518a-5p gene promoter. MiR-518a-5p further influences the levels of p50 and p65 but not p52. HTR8/SVneo cell viability and apoptosis were not influenced by miR-518a-5p. However, miR-518a-5p represses the migratory/invasive capacities of HTR8/SVneo cell and decreased gelatinolytic activity of MMP2 and MMP9, which was reversed by an NF-κB inhibitor. To sum up, miR-518a-5p is induced by NF-κB and represses trophoblast cell migration and invasion by the NF-κB pathway.
Resveratrol (RV) is associated with protection against oxidative stress to improve health, however the effect of RV in layers under oxidative stress (OS) is limited. The objective of this experiment ...was to investigate the negative effect of OS and protective effects of RV against OS in laying hens. 40 Lohmann layers (25-wk-old; BW = 1.44±0.10 kg) were allocated to four treatments in a 2 × 2 factorial arrangement with either RV (0 or 600 mg/kg) or intraperitoneal injection of tert-butyl hydroperoxide (tBHP) (0 or 800 μmol/kg BW) for 31 days. The results shown that the hens challenged with tBHP presented lower egg-laying rate, feed intake, feed efficiency and higher defective egg rate (P(tBHP)<0.05). The RV were also observed to attenuated egg laying rate and feed intake reduction together with decreased broken egg rate under t-BHP challenge (P(Interaction)≤0.01). The tBHP challenged layer demonstrated lower intestinal morphology (villus height in duodenum and jejunum), lower antioxidant enzymes activities total superoxidase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and glutathione (GSH) levels and higher malondialdehyde (MDA) level (P(tBHP)<0.05). Dietary RV increased jejunal SOD, GSH-Px and T-AOC activities, and reduced MDA concentration (P(RV) ≤0.05). Layers under tBHP challenge up-regulated mRNA expression of pro-inflammatory cytokine interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and nuclear factor NF-κB (P(tBHP)<0.05) in jejunum. Dietary RV supplementation down-regulated mRNA gene expression of IL-1β, IL-6, TNF-α and NF-κB (P(RV) ≤0.05). Dietary RV up-regulated mRNA expression of jejunal barrier-related proteins (claudin-1, claudin-2, mucin-1, and occludin) and ovarian reproductive hormone receptor steroidogenic acute regulatory protein (StAR), androgen receptor (AR), estrogen receptor 1 (ESR1), and activin a receptor type 1 (ACVR1) (P(RV) ≤0.05). Overall, the results indicate that tBHP induced oxidative stress to result in reducing production performance, intestinal health and induced ovarian inflammation; whereas dietary RV was able to maintain intestinal health and mitigate the negative impact of tBHP challenge on production performance and ovarian function.
To compare the efficacy and safety of subthreshold micropulse (STMP) laser photocoagulation and half-dose photodynamic therapy (PDT) in the treatment of acute central serous chorioretinopathy (CSC).
...A total of 39 acute CSC patients were included. 18 patients were treated with STMP laser and 21 patients were treated with half-dose PDT. The main outcome measures were best-corrected visual acuity (BCVA) according to Early Treatment Diabetic Retinopathy Study (ETDRS) chart, the proportion of eyes with complete resolution of subretinal fluid, the number of treatments, and the retinal sensitivity by microperimetry during the 12-month study period.
The mean number of treatments during the 12-month period was 1.6 in STMP group and 1.3 in half-dose PDT group, respectively (P = 0.174). The proportion of eyes with complete resolution of subretinal fluid was 83.3% in STMP group compared with 90.5% in half-dose PDT group at 12-month (P = 0.647). The mean BCVA at 12-month after treatment was 75.28 ± 12.58 for STMP group and 76.62 ± 11.57 for half-dose PDT group, respectively (P = 0.731). No statistically significant difference was found in the mean retinal sensitivity between the two groups during the 12 months follow-up (P = 0.701 at 3 months; P = 0.725 at 6 months; P = 0.695 at 12 months).
Subthreshold micropulse Laser Photocoagulation is as effective as half-dose PDT for acute CSC, while minimizing the damage effect on retinal.
Much progress has been made in the area of adaptive designs for clinical trials. However, little has been done regarding adaptive designs to identify optimal treatment strategies in animal studies. ...Motivated by an animal study of a novel strategy for treating strokes, we propose a Bayesian multi-stage cost-effectiveness design to simultaneously identify the optimal dose and determine the therapeutic treatment window for administrating the experimental agent. We consider a non-monotonic pattern for the dose–schedule–efficacy relationship and develop an adaptive shrinkage algorithm to assign more cohorts to admissible strategies. We conduct simulation studies to evaluate the performance of the proposed design by comparing it with two standard designs. These simulation studies show that the proposed design yields a significantly higher probability of selecting the optimal strategy, while it is generally more efficient and practical in terms of resource usage.
Background. In China, little is known regarding the differences between children with Henoch-Schonlein purpura (HSP) and Henoch-Schonlein purpura nephritis (HSPN) concerning their gut microbiota. ...Methods. We recruited 25 children with HSP, 25 children with HSPN, and 25 healthy children to investigate the differences. Fecal samples were collected and analyzed by sequencing the V3-V4 region of the 16S rRNA gene. The diversity of the fecal gut microbiota was compared between the patient groups. Results. Rarefaction curves showed that the gut microbial diversity between the three groups differed significantly (P=0.0224). The top five most abundant gut microbial genera were Bacteroides, Faecalibacterium, Prevotella, Ruminococcaceae, and Megamonas in children with HSP; Bacteroides, Faecalibacterium, Prevotella, Bifidobacterium, and Ruminococcaceae in children with HSPN; and Bacteroides, Prevotella, Faecalibacterium, Ruminococcaceae, and Bifidobacterium in healthy children. Children with HSP had the lowest Bifidobacterium abundance among the three groups (P<0.05). Children with HSPN had a lower abundance of Akkermansia than children with HSP (P<0.05), whereas children with HSPN had a higher Alistipes abundance than children with HSP (P<0.05). Fecal microbial community composition did not differ significantly between groups (ANOSIM, R=−0.002, P=0.46). Despite the small sample size, our results indicate that children with HSP or HSPN displayed dysbiosis of the gut microbiota. Conclusion. This study provides valuable insights that will benefit the development of future microbe-based therapies to improve clinical outcomes or prevent the incidence of HSP or HSPN in children.