The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System (PI-RADS) for standardizing the diagnosis of prostate cancer (PCa). This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen (PSA) <20 ng/ml.
A total of 133 patients with PSA <20 ng/ml were prospectively recruited. T2-weighted (T2WI) and diffusion-weighted (DWI) magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy. Each patient's peripheral zone was divided into six regions on the images; each region corresponded to two of the 12 biopsy cores. T2WI, DWI, and T2WI + DWI scores were computed according to PI-RADS. The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference standard.
PCa was histologically diagnosed in 169 (21.2%) regions. Increased PI-RADS score correlated positively with increased cancer detection rate. The cancer detection rate for scores 1 to 5 was 2.8%, 15.0%, 34.6%, 52.6%, and 88.9%, respectively, using T2WI and 12.0%, 20.2%, 48.0%, 85.7%, and 93.3%, respectively, using DWI. For T2WI + DWI, the cancer detection rate was 1.5% (score 2), 13.5% (scores 3–4), 41.3% (scores 5–6), 75.9% (scores 7–8), and 92.3% (scores 9–10). The area under the curve for cancer detection was 0.700 (T2WI), 0.735 (DWI) and 0.749 (T2WI + DWI). The sensitivity and specificity were 53.8% and 89.2%, respectively, when using scores 5–6 as the cutoff value for T2WI + DWI.
The PI-RADS score correlates with the PCa detection rate in patients with PSA <20 ng/ml. The summed score of T2WI + DWI has the highest accuracy in detection of PCa. However, the sensitivity should be further improved.
Diagnosis; Magnetic Resonance Imaging; Prostate Cancer; Prostate Imaging Reporting and Data System
Embryo implantation is an essential step for the establishment of pregnancy and dynamically regulated by estrogen and progesterone. NDRG4 (N-myc down-regulated gene 4) is a tumor suppressor that participates in cell survival, tumor invasion and angiogenesis. The objective of this study was to preliminarily explore the role of NDRG4 in embryo implantation. By immunohistochemistry (IHC) and quantitive RT-PCR (qRT-PCR), we found that uterine expression of NDRG4 was increased along with puberal development, and its expression in adult females reached the peak at the estrus stage during the estrus cycle. Furthermore, uterine NDRG4 expression was significantly induced by the treatment of estradiol (E2) both in pre-puberty females and ovariectomized adult females. Uterine expression pattern of NDRG4 during the peri-implantation period in mice was determined by IHC, qRT-PCR and Western blot. It was observed that NDRG4 expression was up-regulated during the implantation process, and its expression level at the implantation sites was significantly higher than that at the inter-implantation sites. Meanwhile, an increased expression in NDRG4 was associated with artificial decidualization as well as the activation of delayed implantation. By qRT-PCR and Western blot, we found that the in vitro decidualization of endometrial stromal cells (ESCs) was accompanied by up-regulation of NDRG4 expression, whereas knockdown of its expression in these cells by siRNA inhibited the decidualization process. In addition, Western blot analysis showed that NDRG4 protein expression was decreased in human villus tissues of recurrent miscarriage (RM) patients compared to normal pregnant women. Collectively, these data suggested that uterine NDRG4 expression could be induced by estrogen, and NDRG4 might play an important role during early pregnancy.
To assess the effects of small incision lenticule extraction (SMILE) surgery on the corneal endothelium at 1d to 1mo postoperatively.
A retrospective, observational study was conducted on 47 patients (47 eyes) who received SMILE surgery. Patients were grouped according to contact lens wear condition. The corneal endothelium was examined preoperatively and at 1d, 1wk and 1mo postoperatively. The corneal endothelium was analyzed for endothelial cell density (ECD), percentage of hexagonal cells, and coefficient of variation (CV) of cell size.
There were no significant decrease in the ECD, percentage of hexagonal cells or increase in CV at 1d, 1wk and 1mo postoperatively (P>0.05). However, there was a small increase of ECD by 2.88% in contact lens wearers (78.26±113.62 cell/mm2, P<0.05).
SMILE has no significant adverse effects on the corneal ECD and morphology during 1mo follow-up time.
myopia; corneal endothelium; refractive surgery
To explore the pathogenesis of rheumatoid arthritis (RA), the different metabolites were screened in synovial fluid by metabolomics.
Synovial fluid from 25 RA patients and 10 normal subjects were analyzed by GC/TOF MS analysis so as to give a broad overview of synovial fluid metabolites. The metabolic profiles of RA patients and normal subjects were compared using multivariate statistical analysis. Different proteins were verified by qPCR and western blot. Different metabolites were verified by colorimetric assay kit in 25 inactive RA patients, 25 active RA patients and 20 normal subjects. The influence of hypoxia-inducible factor (HIF)-1α pathway on catabolism was detected by HIF-1α knockdown.
A subset of 58 metabolites was identified, in which the concentrations of 7 metabolites related to energy metabolism were significantly different as shown by importance in the projection (VIP) (VIP≥1) and Student’s t-test (p<0.05). In the 7 metabolites, the concentration of glucose was decreased, and the concentration of lactic acid was increased in the synovial fluid of RA patients than normal subjects verified by colorimetric assay Kit. Receiver operator characteristic (ROC) analysis shows that the concentration of glucose and lactic acid in synovial fluid could be used as dependable biomarkers for the diagnosis of active RA, provided an AUC of 0.906 and 0.922. Sensitivity and specificity, which were determined by cut-off points, reached 84% and 96% in sensitivity and 95% and 85% in specificity, respectively. The verification of different proteins identified in our previous proteomic study shows that the enzymes of anaerobic catabolism were up-regulated (PFKP and LDHA), and the enzymes of aerobic oxidation and fatty acid oxidation were down-regulated (CS, DLST, PGD, ACSL4, ACADVL and HADHA) in RA patients. The expression of HIF-1α and the enzymes of aerobic oxidation and fatty acid oxidation were decreased and the enzymes of anaerobic catabolism were increased in FLS cells after HIF-1α knockdown.
It was found that enhanced anaerobic catabolism and reduced aerobic oxidation regulated by HIF pathway are newly recognized factors contributing to the progression of RA, and low glucose and high lactic acid concentration in synovial fluid may be the potential biomarker of RA.
N-myc down-regulated gene 2 (NDRG2) is a tumor suppressor involved in cell proliferation and differentiation. The aim of this study was to determine the uterine expression pattern of this gene during early pregnancy in mice.
Uterine NDRG2 mRNA and protein expression levels were determined by RT-PCR and Western blot analyses, respectively, during the peri-implantation period in mice. Immunohistochemical (IHC) analysis was performed to examine the spatial localization of NDRG2 expression in mouse uterine tissues. The in vitro decidualization model of mouse endometrial stromal cells (ESCs) was used to evaluate decidualization of ESCs following NDRG2 knock down by small interfering RNA (siRNA). Statistical significance was analyzed by one-way ANOVA using SPSS 19.0 software.
Uterine NDRG2 gene expression was significantly up-regulated and was predominantly localized to the secondary decidual zone on days 5 and 8 of pregnancy in mice. Its increased expression was associated with artificial decidualization as well as the activation of delayed implantation. Furthermore, uterine NDRG2 expression was induced by estrogen and progesterone treatments. The in vitro decidualization of mouse ESCs was accompanied by up-regulation of NDRG2 expression, and knock down of its expression in these cells by siRNA inhibited the decidualization process.
These results suggest that NDRG2 might play an important role in the process of decidualization during early pregnancy.
NDRG2; Embryo implantation; Decidualization
Current development of high-performance transparent conductive oxide (TCO) films is limited with tradeoff between carrier mobility and concentration since none of them can be improved without sacrificing the other. In this study, we prepare fluorine doped tin oxide (FTO) films by chemical vapor deposition with inclusions of different additives and report that the mobility can be varied from 0.65 to 28.5 cm2 V−1 s−1 without reducing the achieved high carrier concentration of 4 × 1020 cm−3. Such an increase in mobility is shown to be clearly associated with the development of (200) preferred orientation (PO) but concurrent degradation of (110) PO in films. Thus, at a constant high carrier concentration, the electrical conductivity can be improved via carrier mobility simply by PO control. Such a one-step approach avoiding conventional post-deposition treatment is suggested for developing next-generation FTO as well as other TCO films with better than ever conductivities.
We demonstrate 40 dB nonreciprocal transmission at telecommunication wavelengths using an integrated all silicon optical diode. The nonreciprocal transmission ratio is the highest to date for CMOS compatible silicon integrated photonics.
An optical diode transmits forward 10Gbps data with less than 0.5dB power penalty, while suppressing and distorting backward data with a 11dB nominal power penalty. The nonreciprocal transmission is also demonstrated with a silicon modulator.
optical nonreciprocity; micro-resonator
In this study, we examined injury progression after intracerebral haemorrhage (ICH) induced by collagenase in mice using a preclinical 11.7 Tesla MRI system. On T2-weighted MRI, lesion and striatal volumes were increased on day 3 and then decreased from days 7 to 28. On day 3, with an increase in striatal water content, vasogenic oedema in the perihaematomal region presented as increased T2 and increased apparent diffusion coefficient (ADC) signal. With a synchronous change in T2 and ADC signals, microglial activation peaked on day 3 in the same region and decreased over time. Iron deposition appeared on day 3 around the haematoma border but did not change synchronously with ADC signals. Vascular permeability measured by Evans blue extravasation on days 1, 3, and 7 correlated with the T1-gadolinium results, both of which peaked on day 3. On diffusion tensor imaging, white matter injury was prominent in the corpus callosum and internal capsule on day 3 and then partially recovered over time. Our results indicate that the evolution of grey/white matter injury and blood-brain barrier disruption after ICH can be assessed with multimodal MRI, and that perihaematomal vasogenic oedema might be attributable to microglial activation, iron deposition, and blood-brain barrier breakdown.
The cytomegaloviruses (CMVs) are among the most genetically complex mammalian viruses, with viral genomes that often exceed 230 kbp. Manipulation of cytomegalovirus genomes is largely performed using infectious bacterial artificial chromosomes (BACs), which necessitates the maintenance of the viral genome in Escherichia coli and successful reconstitution of virus from permissive cells after transfection of the BAC. Here we describe an alternative strategy for the mutagenesis of guinea pig cytomegalovirus that utilizes clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing to introduce targeted mutations to the viral genome. Transient transfection and drug selection were used to restrict lytic replication of guinea pig cytomegalovirus to cells that express Cas9 and virus-specific guide RNA. The result was highly efficient editing of the viral genome that introduced targeted insertion or deletion mutations to nonessential viral genes. Cotransfection of multiple virus-specific guide RNAs or a homology repair template was used for targeted, markerless deletions of viral sequence or to introduce exogenous sequence by homology-driven repair. As CRISPR/Cas9 mutagenesis occurs directly in infected cells, this methodology avoids selective pressures that may occur during propagation of the viral genome in bacteria and may facilitate genetic manipulation of low-passage or clinical CMV isolates.
IMPORTANCE The cytomegalovirus genome is complex, and viral adaptations to cell culture have complicated the study of infection in vivo. Recombineering of viral bacterial artificial chromosomes enabled the study of recombinant cytomegaloviruses. Here we report the development of an alternative approach using CRISPR/Cas9-based mutagenesis in guinea pig cytomegalovirus, a small-animal model of congenital cytomegalovirus disease. CRISPR/Cas9 mutagenesis can introduce the same types of mutations to the viral genome as bacterial artificial chromosome recombineering but does so directly in virus-infected cells. CRISPR/Cas9 mutagenesis is not dependent on a bacterial intermediate, and defined viral mutants can be recovered after a limited number of viral genome replications, minimizing the risk of spontaneous mutation.
Driven by the increasing demand on handing microwave signals with compact device, low power consumption, high efficiency and high reliability, it is highly desired to generate, distribute, and process microwave signals using photonic integrated circuits. Silicon photonics offers a promising platform facilitating ultracompact microwave photonic signal processing assisted by silicon nanophotonic devices. In this paper, we propose, theoretically analyze and experimentally demonstrate a simple scheme to realize ultracompact rejection ratio tunable notch microwave photonic filter (MPF) based on a silicon photonic crystal (PhC) nanocavity with fixed extinction ratio. Using a conventional modulation scheme with only a single phase modulator (PM), the rejection ratio of the presented MPF can be tuned from about 10 dB to beyond 60 dB. Moreover, the central frequency tunable operation in the high rejection ratio region is also demonstrated in the experiment.
A promising alternative route for the synthesis of three-dimensional Au dendrites was developed by direct electrodeposition from a solution of HAuCl4 containing 3-aminopropyltriethoxysilane (APTS). Ultraviolet-visible spectroscopy, fourier transform infrared spectroscopy and isothermal titration calorimetry were used to study the interaction of APTS in electrolyte. The effect of APTS on the formation of the hierarchical structure of Au dendrites was investigated by cyclic voltammetry, rotating disk electrode, electrochemical impedance spectroscopy and quartz crystal microbalance. The growth directions of the trunks and branches of the Au dendrites can be controlled by sweep-potential electrodeposition to obtain more regular structures. The efficacy of as-synthesised Au dendrites was demonstrated in the enhanced electro-catalytic activity to methanol electro-oxidation and the high sensitivity of glucose detection, which have potential applications in direct-methanol fuel cells and non-enzymatic electrochemical glucose biosensors, respectively.
Recent studies have shown that haloarchaea employ leaderless and Shine-Dalgarno (SD)-less mechanisms for translation initiation of leaderless transcripts with a 5′ untranslated region (5′ UTR) of <10 nucleotides (nt) and leadered transcripts with a 5′ UTR of ≥10 nt, respectively. However, whether the two mechanisms can operate on the same naturally occurring haloarchaeal transcript carrying multiple potential start codons is unknown. In this study, the transcript of the sptA gene (encoding an extracellular serine protease of Natrinema sp. strain J7-2) was experimentally determined and found to contain two potential in-frame AUG codons (AUG1 and AUG2) located 5 and 29 nt, respectively, downstream of the transcription start site. Mutational analysis revealed that both AUGs can function as the translation start codon for production of active SptA, although AUG1 is more efficient than AUG2 for translation initiation. Insertion of a stable stem-loop structure between the two AUGs completely abolished initiation at AUG1 but did not affect initiation at AUG2, indicating that AUG2-initiated translation does not involve ribosome scanning from the 5′ end of the transcript. Furthermore, the efficiency of AUG2-initiated translation was not influenced by an upstream SD-like sequence. In addition, both AUG1 and AUG2 contribute to transcript stability, probably by recruiting ribosomes to protect the transcript against degradation. These data suggest that depending on which of two in-frame start codons is used, the sptA transcript can act as either a leaderless or a leadered transcript for SptA production in haloarchaea.
IMPORTANCE In eukaryotes and bacteria, alternative translation start sites contribute to proteome complexity and can be used as a functional mechanism to increase translation efficiency. However, little is known about alternative translation initiation in archaea. Our results demonstrate that leaderless and SD-less mechanisms can be used for translation initiation of the sptA transcript from two in-frame start codons, raising the possibility that in haloarchaea, alternative translation initiation on one transcript functions to increase translation efficiency and/or contribute to proteome complexity.
High glucose in vivo and in vitro induces neural tube defects (NTDs). CITED2 (CBP/p300-interacting transactivator with ED-rich tail 2) is essential for neural tube closure. We explored the regulatory mechanism underlying CITED2 expression and its relationship with miRNA and endoplasmic reticulum (ER) stress. miR-200b levels were increased by maternal diabetes or high glucose in vitro, and this increase was abrogated by transgenic overexpression of superoxide dismutase 1 (SOD1) or an SOD1 mimetic. CITED2 was the target of miR-200b and was downregulated by high glucose. Two miR-200b binding sites in the 3′-untranslated region of the CITED2 mRNA were required for inhibiting CITED2 expression. The miR-200b mimic and a CITED2 knockdown mimicked the stimulative effect of high glucose on unfolded protein response (UPR) and ER stress, whereas the miR-200b inhibitor and CITED2 overexpression abolished high glucose–induced UPR signaling, ER stress, and apoptosis. The ER stress inhibitor, 4-phenylbutyrate, blocked CITED2 knockdown–induced apoptosis. Furthermore, the miR-200b inhibitor reversed high glucose–induced CITED2 downregulation, ER stress, and NTDs in cultured embryos. Thus, we showed a novel function of miR-200b and CITED2 in high glucose–induced UPR and ER stress, suggesting that miR-200b and CITED2 are critical for ER homeostasis and NTD formation in the developing embryo.
To quantify and predict the economic burden of dementia in China for the periods 1990–2010 and 2020–2030, respectively, and discuss the potential implications for national public health policy.
Using a societal, prevalence-based, gross cost-of-illness approach and data from multiple sources, we estimated or predicted total annual economic costs of dementia in China. We included direct medical costs in outpatient and inpatient settings, direct non-medical costs – e.g. the costs of transportation – and indirect costs due to loss of productivity. We excluded comorbidity-related costs.
The estimated total annual costs of dementia in China increased from 0.9 billion United States dollars (US$) in 1990 to US$ 47.2 billion in 2010 and were predicted to reach US$ 69.0 billion in 2020 and US$ 114.2 billion in 2030. The costs of informal care accounted for 94.4%, 92.9% and 81.3% of the total estimated costs in 1990, 2000 and 2010, respectively. In China, population ageing and the increasing prevalence of dementia were the main drivers for the increasing predicted costs of dementia between 2010 and 2020, and population ageing was the major factor contributing to the growth of dementia costs between 2020 and 2030.
In China, demographic and epidemiological transitions have driven the growth observed in the economic costs of dementia since the 1990s. If the future costs of dementia are to be reduced, China needs a nationwide dementia action plan to develop an integrated health and social care system and to promote primary and secondary prevention.
This study sought to develop a reliable and easy-to-use scoring model to guide the decision to perform postsurgical adjuvant transarterial chemoembolization (PA-TACE) in patients with hepatitis B-related hepatocellular carcinoma (HCC).
The study included 235 consecutive patients with hepatitis B-related HCC undergoing PA-TACE at our medical center. Patients were assigned to 2 sets according to the PA-TACE date: initial (2005–2007; n = 130) and internal validation (2008–2009; n = 105) sets. With the aid of a Cox regression model, we developed a risk-scoring model from the independent predictive factors of our initial set designed as a guide for PA-TACE, and the performance of the model was validated with an internal set. External validation was also performed with an independent dataset (n = 84) to assess the discriminatory power of the scoring model.
In the multivariate analysis, 4 risk factors (an increase in Child-Pugh score of at least 1 point, hepatitis B virus deoxyribonucleic acid [HBV-DNA] level >104 IU/mL, tumor diameter ≥5 cm, and the presence of vascular invasion) were significantly associated with prognosis. These factors were incorporated into a novel clinicopathological scoring model (assessment for PA-TACE [APT] risk-scoring model) ranging from 0 to 8 that was correlated with prognosis. Different survival outcomes were identified in three groups (0–2 points, 3–6 points, and 7–8 points). The risk-scoring model was further confirmed with 2 independent sets.
The novel APT risk-scoring model, merging 4 prognostic factors, may achieve an optimal postsurgical prediction of PA-TACE in HBV-related HCC. The risk for an individual patient with an APT score of ≥7.0 prior to the PA-TACE, who may not profit from further PA-TACE, can be determined, and this may lead to a more appropriate choice of treatment.
adjuvant transarterial chemoembolization; hepatitis B-related hepatocellular carcinoma; postsurgical treatment
Benign prostatic hyperplasia is a common progressive disease in aging men, which leads to a significant impact on daily lives of patients. Continuous bladder irrigation (CBI) is a supplementary option for preventing the adverse events following transurethral resection of the prostate (TURP). Regulation of the flow rate based on the color of drainage bag is significant to prevent the clot formation and retention, which is controlled manually at present. To achieve a better control of flow rate and reduce inappropriate flow rate–related adverse effects, we designed an automatic flow rate controller for CBI applied with wireless sensor and evaluated its clinical efficacy.
The therapeutic efficacy was evaluated in patients receiving the novel automatic bladder irrigation post-TURP in the experimental group compared with controls receiving traditional bladder irrigation in the control group.
A total of 146 patients were randomly divided into 2 groups—the experimental group (n = 76) and the control group (n = 70). The mean irrigation volume of the experimental group (24.2 ± 3.8 L) was significantly lower than that of the controls (54.6 ± 5.4 L) (P < 0.05). Patients treated with automatic irrigation device had significantly decreased incidence of clot retention (8/76) and cystospasm (12/76) compared to controls (21/70; 39/70, P < 0.05). There was no significant difference between the 2 groups with regard to irrigation time (28.6 ± 2.7 vs 29.5 ± 3.4 hours, P = 0.077).
The study suggests that the automatic regulating device applied with wireless sensor for CBI is safe and effective for patients after TURP. However, studies with a large population of patients and a long-term follow-up should be conducted to validate our findings.
automatic regulating device; continuous bladder irrigation; transurethral resection of the prostate; wireless sensor
Background. Esophagogastric variceal hemorrhage leads to challenging situation in chronic kidney disease patients on maintenance hemodialysis. Aims. To determine the safety and efficacy of endoscopic approaches to patients with hemodialysis-dependent concomitant with esophagogastric varices. Methods. Medical records were reviewed from January 1, 2004, to December 31, 2015, in our hospital. Five consecutive hemodialysis-dependent patients with variceal hemorrhage who underwent endoscopic treatments were retrospectively studied. Results. The median age of the patients was 54 years (range 34–67 years) and the median follow-up period was 21.3 months (range 7–134 months). All the patients received a total of three times heparin-free hemodialysis 24 hours before and no more than 24 hours and 72 hours after endoscopic treatment. They successfully had endoscopic variceal ligation, endoscopic injection sclerotherapy, and/or N-butyl cyanoacrylate injection. The short-term efficacy is satisfying and long-term follow-up showed episodes of rebleeding. Conclusions. Endoscopic approaches are the alternative options in the treatment of upper gastroenterology variceal hemorrhage in hemodialysis-dependent patients without severe complications.
CD44 polymorphisms have been previously associated with cancer risk. However, the results between independent studies were inconsistent. Here, a meta-analysis was performed to systematically evaluate associations between CD44 polymorphisms and cancer susceptibility. A comprehensive literature search conducted in PubMed, Embase, and Web of Science databases through August 10, 2016 yielded 11 eligible publications consisting of 5,788 cancer patients and 5,852 controls. Overall, odds ratios (OR) calculated with 95% confidence intervals (CI) identified a significant association between CD44 polymorphism rs13347 and cancer susceptibility under all genetic models. Additionally, the minor allele of polymorphism rs11821102 was associated with a decreased susceptibility to cancer in allele contrast, dominant, and heterozygous models, while no significant association was identified for polymorphisms rs10836347, rs713330, or rs1425802. Subgroup analysis by ethnicity revealed rs13347 was significantly associated with cancer susceptibility for Chinese but not for Indians. Linkage disequilibrium (LD) between different polymorphisms varied across diverse ethnic populations. In conclusion, the results indicate that CD44 polymorphism rs13347 acts as a risk factor for cancer, especially in Chinese, while the minor allele of polymorphism rs11821102 may be associated with a decreased susceptibility to cancer. Nevertheless, further studies on a larger population covering different ethnicities are warranted.
To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria.
The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated.
Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage (VH). No major adverse events were identified.
The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.
panretinal photocoagulation; intravitreal bevacizumab; high-risk proliferative diabetic retinopathy; neovascularization on the disc
A vaccine to prevent congenital cytomegalovirus (CMV) infections is a national priority. Investigational vaccines have targeted the viral glycoprotein B (gB) as an inducer of neutralizing antibodies and phosphoprotein 65 (pp65) as an inducer of cytotoxic T cells. Antibodies to gB neutralize CMV entry into all cell types but their potency is low compared to antibodies that block epithelial cell entry through targeting the pentameric complex (gH/gL/UL128/UL130/UL131). Hence, more potent overall neutralizing responses may result from a vaccine that combines gB with pentameric complex-derived antigens. To assess the ability of pentameric complex subunits to generate epithelial entry neutralizing antibodies, DNA vaccines encoding UL128, UL130, and/or UL131 were formulated with Vaxfectin®, an adjuvant that enhances antibody responses to DNA vaccines. Mice were immunized with individual DNA vaccines or with pair-wise or trivalent combinations. Only the UL130 vaccine induced epithelial entry neutralizing antibodies and no synergy was observed from bi- or trivalent combinations. In rabbits the UL130 vaccine again induced epithelial entry neutralizing antibodies while UL128 or UL131 vaccines did not. To evaluate compatibility of the UL130 vaccine with DNA vaccines encoding gB or pp65, mono-, bi-, or trivalent combinations were evaluated. Fibroblast and epithelial entry neutralizing titers did not differ between rabbits immunized with gB alone vs. gB/UL130, gB/pp65, or gB/UL130/pp65 combinations, indicating a lack of antagonism from coadministration of DNA vaccines. Importantly, gB-induced epithelial entry neutralizing titers were substantially higher than activities induced by UL130, and both fibroblast and epithelial entry neutralizing titers induced by gB alone as well as gB/pp65 or gB/UL130/pp65 combinations were comparable to those observed in sera from humans with naturally-acquired CMV infections. These findings support further development of Vaxfectin®-formulated gB-expressing DNA vaccine for prevention of congenital CMV infections.
cytomegalovirus; vaccine; neutralizing antibody
Huangqin-tang (HQT) is a traditional Chinese medicine (TCM) formula widely used for the treatment of inflammatory bowel disease in China. However, the molecular mechanisms by which HQT protects the colon are unclear. We studied the protective effects of HQT and the underlying mechanisms in an experimental mouse model and in vitro. In vivo, dextran sodium sulphate (DSS)-induced acute and chronic colitis were significantly ameliorated by HQT as gauged by phenotypic, histopathologic and inflammatory manifestations of the disease. Mechanistically, DSS-induced nuclear factor-κB (NF-κB) signalling was inhibited by HQT. Moreover, HQT-treated mice demonstrated significant changes in cell apoptosis, expression of apoptosis-associated genes such as caspase-3, bax, bcl-2, and intestinal permeability. HQT also increased occluding and zonula occludens-1 (ZO-1), inhibited cell proliferation (Ki67), and increased regulatory T cells numbers, protein expression of Foxp3 and IL-10 in the colonic tissue. In vitro, HQT down-regulated production of pro-inflammatory cytokines and supressed the NF-κB signalling pathway in lipopolysaccharides-induced RAW 264.7 macrophages. Our study suggests that HQT plays a critical role in regulating intestinal epithelial cell homeostasis, inflammation and immune response in colitis and offers novel therapeutic options in the management of inflammatory bowel disease.
Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A20−/− and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A20−/− and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A20−/− parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICH-induced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A20−/− parabionts compared with A20−/− mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A20−/− mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IκBα degradation and NF-κB activation were observed in A20−/− mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH.
To evaluate the efficacy and safety of nitrous oxide-sedated endoscopic ultrasound-guided fine needle aspiration.
Enrolled patients were divided randomly into an experimental group (inhalation of nitrous oxide) and a control group (inhalation of pure oxygen) and heart rate, blood oxygen saturation, blood pressure, electrocardiogram (ECG) changes, and the occurrence of complications were monitored and recorded. All patients and physicians completed satisfaction questionnaires about the examination and scored the process using a visual analog scale.
There was no significant difference in heart rate, blood oxygen saturation, blood pressure, ECG changes, or complication rate between the two groups of patients (P > 0.05). However, patient and physician satisfaction were both significantly higher in the nitrous oxide compared with the control group (P < 0.05).
Nitrous oxide-sedation is a safe and effective option for patients undergoing endoscopic ultrasound-guided fine needle aspiration.
Endoscopic ultrasonography; Nitrous oxide; Sedation; Fine needle aspiration