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Proton therapy is a rapidly progressing modality with a significant impact on lung cancer treatment. However, there are concerns about the subsequent effects of secondary radiation in out-of-field organs. Thus, the present study aimed to evaluate the risk of subsequent secondary cancers within non-target organs during proton therapy for lung cancer. A Monte Carlo model of the International Commission on Radiological Protection (ICRP) 110 male phantom was employed to calculate the absorbed dose associated with secondary photons and neutrons within out-of-field organs for different tumor locations. The risk of induced secondary cancers was then estimated using the Biological Effects of Ionizing Radiation Committee (BEIR) VII and National Council on Radiation Protection and Measurements (NCRP) 116 risk models. Organs close to the tumor, such as the heart, esophagus, thymus, and liver, received the highest equivalent doses. The calculated equivalent doses increased as the tumor depth increased from 4-8 cm to 12-16 cm. The contribution of neutrons to the total equivalent dose was dominant (up to 90%) in most of the organs studied. The calculated risks of secondary cancers were higher in the liver and esophagus compared with other organs when using the BEIR risk model. The maximum risk value was obtained for the left lung when the NCRP 116 risk model was used. Furthermore, the estimated risks of secondary malignancies increased with the tumor depth using both risk models. The calculated risks of radiation-induced secondary cancers were relatively lower than the baseline cancer risks. However, extra attention is warranted to minimize subsequent secondary cancers after proton therapy for lung cancer., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below the manuscript title certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach., Material and Methods: A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure., Results: The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm 2 to 8 × 10 cm 2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages., Conclusion: Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied., Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI., Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023., Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI., Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively)., Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08)., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Aims: Heart failure (HF) is a progressive disease with recurrent hospitalizations and high mortality. However, the mechanisms underlying HF remain unclear. The present study aimed to explore the regulatory mechanism of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1)/Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1) axis in HF., Methods: The HF rat models and hypertrophy cell models were established. The characteristic parameters of the heart were detected by echocardiography. A multichannel physiological signal acquisition system was used to detect the hemodynamic parameters. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HDAC3, DNMT1, and SHP-1 mRNAs, while Western blot was applied to analyze the expression of proteins. Masson staining was used to analyze the degree of collagen fiber infiltration. TdT-mediated DUTP nick end labeling (TUNEL) staining was performed to analyze the apoptosis of myocardial tissue cells. Co-immunoprecipitation (co-IP) was conducted to study the interaction between HDAC3 and DNMT1. Flow cytometry was used to analyze the apoptosis., Key Findings: HDAC3 and DNMT1 were highly expressed in HF rat and hypertrophy cell models. HDAC3 modified DNMT1 through deacetylation to inhibit ubiquitination-mediated degradation, which promoted the expression of DNMT1. DNMT1 inhibited SHP-1 expression via methylation in the promoter region. In summary, HDAC3 modified DNMT1 by deacetylation to suppress SHP-1 expression, which in turn led to the development of cardiomyocyte hypertrophy-induced HF., Significance: This study provided potential therapeutic targets for HF treatment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to compare the salivary biochemical indices between caries-free individuals and those with early childhood caries (ECC), and construct a saliva-based caries diagnostic model by analyzing the correlation between salivary biochemical indices and caries severity., Methods: A total of 120 children aged 4-6 years were selected and divided into two groups: individuals with ECC (C group, n =60) and healthy children (H group, n =60). Salivary samples were collected to compare the pH, total protein, and ion concentrations between the two groups. The correlation between the salivary biochemical indices and caries severity was examined, and an ECC diagnostic model was established., Results: The NO 3 - concentration significantly decreased in the C group, whereas the Cl - , Br - , NH 4 + , and Mg 2+ concentrations significantly increased in the C group ( P <0.05). In addition, the salivary caries severity had a significantly negative correlation with the NO 3 - concentration but had a positive correlation with Br - , Cl - , and NH 4 + concentrations ( P <0.05). The ECC diagnostic model based on salivary biochemical indices could yield satisfactory results in terms of distinguishing the C and H groups with over 85% accuracy., Conclusions: Salivary biochemical indices can contribute to the diagnosis and risk assessment of ECC.

Hansenia Turcz., Haplosphaera Hand.-Mazz. and Sinodielsia H.Wolff are three Apiaceae genera endemic to the Hengduan Mountains and the Himalayas, which usually inhabit elevations greater than 2000 m. The phylogenetic relationships between and within the genera were uncertain, especially the placement of Hap. himalayensis and S. microloba . Therefore, we aimed to conduct comparative (simple sequence repeat (SSR) structure, codon usage bias, nucleotide diversity (Pi) and inverted repeat (IR) boundaries) and phylogenetic analyses of Hansenia , Haplosphaera and Sinodielsia (also compared with Chamaesium and Bupleurum ) to reduce uncertainties in intergeneric and interspecific relationships. We newly assembled eight plastid genomes from Hansenia , Haplosphaera and Sinodielsia species, and analyzed them with two plastid genomes from GenBank of Hap. phaea, S. yunnanensis . Phylogenetic analyses used these ten genomes and another 22 plastid genome sequences of Apiaceae. We found that the newly assembled eight genomes ranged from 155,435 bp to 157,797 bp in length and all had a typical quadripartite structure. Fifty-five to 75 SSRs were found in Hansenia , Haplosphaera and Sinodielsia species, and the most abundant SSR was mononucleotide, which accounted for 58.47% of Hansenia , 60.21% of Haplosphaera and 48.01% of Sinodielsia. There was no evident divergence of codon usage frequency between the three genera, where codons ranged from 21,134 to 21,254. The Pi analysis showed that trnE(UUC)-trnT(GGU) , trnH(GUG)-psbA and trnE(UUC)-trnT(GGU) spacer regions had the highest Pi values in the plastid genomes of Hansenia (0.01889), Haplosphaera (0.04333) and Sinodielsia (0.01222), respectively. The ndhG-ndhI spacer regions were found in all three genera to have higher diversity values (Pi values: 0.01028-0.2), and thus may provide potential DNA barcodes in phylogenetic analysis. IR boundary analysis showed that the length of rps19 and ycf1 genes entering IRs were usually stable in the same genus. Our phylogenetic tree demonstrated that Hap. himalayensis is sister to Han. weberbaueriana ; meanwhile, Haplosphaera and Hansenia are nested together in the East Asia clade, and S. microloba is nested within individuals of S. yunnanensis in the Acronema clade. This study will enrich the complete plastid genome dataset of the Apiaceae genera and has provided a new insight into phylogeny reconstruction using complete plastid genomes of Hansenia , Haplosphaera and Sinodielsia .

To validate the GATE Monte Carlo simulation code and to investigate the lateral scattering of proton pencil beams in the major body tissue elements in the therapeutic energy range. In this study, GATE Monte Carlo simulation code was used to compute absorbed dose and fluence of protons in a water cubic phantom for the clinical energy range. To apply the suitable physics model for simulation, different physics lists were investigated. The present research also investigated the optimal value of the water ionization potential as a simulation parameter. Thereafter, the lateral beam profile of proton pencil beams were simulated at different energies and depths in body tissue elements. The range results obtained using the QGSP&#95;BIC&#95;EMY physics showed the best compatibility with the NIST database data. Moreover, it was found that the 76 eV is the optimal value for the water ionization potential. In the next step, it was shown that the beam halo can be described by adding a supplementary Gaussian function to the standard single-Gaussian model, which currently is used by treatment planning systems (TPS)., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: The purpose of this study was to investigate the crosstalk effects between adjacent pixels in a thin silicon detector with 50 um thickness., Background: There are some limitations in the applications of detectors in hadron therapy. So it is necessary to have a detector with concurrent excellent time and resolution. In this work, the GEANT4 toolkit was applied to estimate the best value for energy cutoff in the thin silicon detector in order to optimize the detector., Materials and Methods: GEANT4 toolkit was applied to simulate the transport and interactions of particles. Calculations were performed for a thin silicon detector (2 cm × 2 cm×0.005 cm) irradiated by proton and carbon ion beams. A two-dimensional array of silicon pixels in the x-y plane with 100 um × 100 um × 50 um dimensions build the whole detector. In the end, the ROOT package is used to interpret and analyze the results., Results: It is seen that by the presence of energy cutoff, pixels with small deposited energy are ignored. The best values for energy cutoff are 0.01 MeV and 0.7 MeV for proton and carbon ion beams, respectively. By applying these energy cutoff values, efficiency and purity values are maximized and also minimum output errors are achieved., Conclusions: The results are reasonable, good and useful to optimize the geometry of future silicon detectors in order to be used as beam monitoring in hadron therapy applications., (© 2019 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

Background: Patients with ST-segment elevation myocardial infarction (STEMI) who present without typical chest pain are associated with a poor outcome. However, whether angiographic characteristics are related to a higher risk of mortality in this population is unclear. This study aimed to investigate whether the higher mortality risk in patients with STEMI without chest pain could be explained by their "high-risk" angiographic characteristics., Methods: We used data of 12,145 patients with STEMI who was registered in China Acute Myocardial Infarction registry from January 2013 to September 2014. We compared the infarct-related artery (IRA), thrombolysis in myocardial infarction (TIMI) flow grade in the IRA, and other angiographic characteristics between patients without and those with chest pain. Multivariable logistic regression model was used to identify independent risk factor of in-hospital mortality., Results: The 2922 (24.1%) patients with STEMI presented without typical chest pain. These patients had a higher TIMI flow grade (mean TIMI flow grade: 1.00 vs. 0.94, P = 0.02) and a lower rate of IRA disease of the left anterior descending artery (44.6% vs. 51.2%, χ = 35.63, P < 0.01) than did those with typical chest pain. Patients without chest pain were older, more likely to have diabetes, longer time to hospital and higher Killip classification, and less likely to receive optimal medication treatment and primary percutaneous coronary intervention and higher In-hospital mortality (3.3% vs. 2.2%, χ = 10.57, P < 0.01). After adjusting for multi-variables, presentation without chest pain was still an independent predictor of in-hospital death among patients with STEMI (adjusted odds ratio: 1.36, 95% confidence interval: 1.02-1.83)., Conclusions: Presentation without chest pain is common and associated with a higher in-hospital mortality risk in patients with acute myocardial infarction. Our results indicate that their poor prognosis is associated with baseline patient characteristics and delayed treatment, but not angiographic lesion characteristics., Clinical Trial Registration: NCT01874691, https://clinicaltrials.gov.

Tongoloa silaifolia , known as a traditional Chinese medicine Taibaisanqi, is a perennial herb of Apiaceae. In this study, the complete chloroplast genome of T. silaifolia was determined through Illumina sequencing method. The chloroplast genome of T. silaifolia was 161,122 bp in length and contained a pair of IR regions (30,824 bp) separated by a small single-copy region (17,553 bp) and a large single-copy region (81,921 bp). This chloroplast genome is encoded with 137 genes including 92 CDS, 37 tRNA genes, and 8 rRNA genes. The overall GC content of T. silaifolia cp genome is 37.7%. By phylogenetic analysis using maximum likelihood method, T. silaifolia showed the closest relationship with Chuanminshen violaceum and Hansenia species., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To compare the efficacy and safety of active transfer of plaque (ATP) versus provisional stenting (PS) with drug-eluting stents (DES) for the treatment of coronary bifurcation lesions. Methods: A total of 1 136 patients with bifurcation lesions hospitalized in 6 selected hospitals between January 2010 and January 2014 were included in this prospective observational trial, patients were divided into either ATP ( n= 560) or PS group ( n= 576) accordingly. The primary endpoint was target lesion revascularization within 1 year, and the second endpoints were all-cause death, cardiogenic death, myocardial infarction, stent thrombosis, stroke, recurrent angina within 1 year. Results: There were no significant differences in age, sex, hypertension, diabetes, hyperlipidemia and smoking history between the two groups ( P> 0.05). The incidence of TIMI blood flow <3 grade in the side branch (1.6%(9/560) vs. 7.5% (43/576), P< 0.01), acute occlusion of the side branch (1.3%(7/560) vs. 7.1%(41/576), P< 0.01) and implanted stents of side branch (1.8%(10/560) vs. 7.8% (45/576), P< 0.01) were significantly lower in the ATP group than those in the PS group. During the one year follow up, the rate of target lesion revascularization was similar between ATP group and PS group (4.6%(26/560) vs. 4.0%(23/576), P= 0.66). Conclusions: The effectiveness and safetyof ATP techniquein the patients with coronary bifurcation lesions is comparable to the PS technique. However, ATP technique is superior to PS technique on effectively reducing the incidence of implanted stents in the side branch.

Aim: To compare the benefits and potential harms of routine phacoemulsification (phaco) alone and combined surgery with goniosynechialysis (GSL) for angle-closure glaucoma (ACG) and coexisting lens opacity, as shown in different randomized controlled trials (RCTs)., Methods: A systematic review was conducted searching several databases including PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov from the inception to September 2018 for RCTs with data published on the effects and safety of phaco and intraocular lens implantation combined with GSL or routine cataract surgery alone. Several studies were recruited which reported data at baselines and postoperative follow-up, including the mean values of postoperative intraocular pressure (IOP) and mean numbers of anti-glaucoma medications using postoperatively. The numbers of complications happening were also included. Fixed-effect and random-effect models were applied, and the quality of evidence was evaluated., Results: Analysis of the seven included RCTs, with a total number of 321 participants (358 eyes) diagnosed with ACG and cataract, received a solo procedure (phaco group) or a combined surgery (phaco-GSL group) randomly, and follow-up periods ranging from 2 to 12mo postoperatively. The involved studies showed that the mean value of IOP between the two groups at 3 (four studies, one study follow-up at 2mo postoperative was included), 6, 12mo postoperative were not significantly different. Only two studies reported the change in IOP value at 12mo compared with baseline but showed no significant differences between the two interventions. Although three studies did not have the significant difference in the number of medications using to reduce IOP at 3mo postoperatively, two studies reported that the participants using fewer anti-glaucoma medications at 12mo postoperative in the phaco group than in the phaco-GSL surgery group., Conclusion: The analysis provides a low to moderate-quality evidence that phaco-GSL surgery lead to an equivalent IOP-lowering effect. The phaco-GSL surgery may not help patients to reduce the consumption of anti-glaucoma eyedrops in the long period. The results of this analysis suggested that additional GSL may not be necessary for primary angle closure glaucoma (PACG) patients. Further studies, especially RCTs with more participants and longer follow-up time were needed to provide more sufficient data.

Background: Diabetic retinopathy (DR) is currently the leading cause of blindness and visual disability in adults with diabetes mellitus (DM). Neovascularization has been identified as an important clinical property in DR, however, the exact mechanisms in DR neovascularization are still unclear and need further elucidation. Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of long non-coding RNA (lncRNA)-metastasis associated lung adenocarcinoma transcript 1 (MALAT1), miR-125b and vascular endothelial-cadherin (VE-cadherin) in human retina microvascular endothelial cells (hRMECs) treated with high glucose (HG). Luciferase assay was used to detect interaction of MALAT1 with miR-125b and miR-125b with VE-cadherin. MTT assay, transwell assay, tube formation assay and vascular permeability assay were conducted to detect the cell viability, migration tube formation ability and permeability of hRMECs, respectively. ELISA was used to examine the release of VE-cadherin and vascular endothelial growth factor (VEGF). Western blotting was used to access the protein expression of VE-cadherin, VEGF, β-catenin, matrix metalloproteinase (MMP) 2 (MMP2) and MMP9. Results: MALAT1 and VE-cadherin were up-regulated while miR-125b was down-regulated in hRMECs treated with HG. MALAT1 could competitively bind to miR-125b against VE-cadherin at the site of 3'-untranslated region (3'-UTR), leading to the up-regulation of VE-cadherin. Knockdown of MALAT1 inhibited the proliferation, migration, tube formation and vascular permeability of hRMECs induced by HG through up-regulating miR-125b. Furthermore, we found the deletion of MALAT1 suppressed the VE-cadherin/β-catenin complex and neovascularization related proteins expression, which was up-regulated by HG. Conclusion: Knockdown of MALAT1 inhibited cell proliferation, migration and angiogenesis of hRMECs via suppressing the VE-cadherin/β-catenin complex through targeting miR-125b. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for DR., (© 2019 The Author(s).)

Aim: To investigate the regulation and mechanisms of periostin expression in retinal Müller glia, and to explore the relevance to retinal neovascularization., Methods: The oxygen-induced retinopathy (OIR) mouse model and the human Moorfield/Institute of Ophthalmology-Müller 1 (MIO-M1) cell line were used in the study. Immunofluorescence staining was used to determine the distribution and expression of periostin and a Müller glial cell marker glutamine synthetase (GS). Cytokines TNF-α and IFN-γ were added to stimulate the MIO-M1 cells. ShRNA was used to knockdown periostin expression in MIO-M1 cells. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess the mRNA expression of periostin., Results: Immunofluorescence staining showed that periostin was expressed by MIO-M1 Müller glia. GS-positive Müller glia and periostin increased in OIR retinas, and were partially overlaid. The stimulation of TNF-α and IFN-γ reduced the mRNA expression of periostin significantly and dose-dependently in MIO-M1 cells. Knockdown of periostin reduced mRNA expression of vascular endothelial growth factor A (VEGFA) in MIO-M1 cells, while VEGFA expression was not changed in periostin knock-out OIR retinas., Conclusion: Müller glia could be one of the main sources of periostin in the retina, and might contribute to the pathogenesis of retinal neovascularization. Proinflammatory cytokines TNF-α and IFN-γ attenuate the periostin expression in retinal Müller glia, which provides a potential and novel method in treating retinal neovascular diseases.

The present review describes recent advances in application of accommodating intraocular lenses (AIOLs). Standard monofocal intraocular lenses (MIOLs) only correct distance vision, while AIOLs are designed to allow both good distance vision and near vision, which is achieved through the contraction and relaxation of ciliary muscles by providing transformation of the axial movement or curvature of the lens. Thus, AIOLs may be a better choice for those patients who demand a higher level of visual performance. Since techniques to analyze the performance of AIOLs have not been standardized, and there is a variety of both subjective and objective methods, it is hard to measure the performance of these intraocular lenses. By evaluating advantages and disadvantages of various AIOLs, and introducing techniques for measurement the performance postoperative, this paper can provide some relative information on choosing the type of AIOLs in the clinic.

Objective: To compare the salivary microbial profiles of healthy subjects and those with severe early childhood caries (S-ECC) by using high-throughput sequencing., Methods: Salivary samples were obtained from children with S-ECC (group C, n=24) and healthy children (group H, n=24). Total metagenomic DNA was extracted, and DNA amplicons of the V1-V3 hypervariable region of the 16S rRNA gene were generated and subjected to 454 sequencing. The characteristics of oral microbial communities from the two groups were compared based on microbial diversity and taxonomy assignment., Results: First, the microbial richness was significantly higher in group C than group H (P<0.05). Second, the microbial community structure was significantly different for the groups H and C (P<0.01). In addition, caries microbiota was significantly conserved in group C (P<0.001). High expression of suspected cariogenic microorganisms in group C (P<0.1) and health related microorganisms in group H (P<0.1) were identified. Finally, models of caries risk assessment were proposed to distinguish caries from healthy subjects with over 70% accuracy., Conclusions: Salivary microbiota and certain taxa, such as caries-associated taxa (Prevotella), may be useful to screen/assess the children's risk of developing caries.

We describe the male of Sinhomidia bicolor for the first time noting a morphological difference from the female. A new species, Sinhomidia guangxiensis sp. nov. is described and illustrated. The new species differs from S. bicolor by the appendages lacking scales, the mucronal basal spine reaching the apex of subapical tooth, the number of chaetae on the trochanteral organ and the distribution of macrochaetae on Th. II, Abd I and Abd II. A key to Sinhomidia species and a diagnostic table to separate male and female S. bicolor and the new species are provided.

Aim: The aim of this study is to evaluate the effect of soft tissue composition on dose distribution and spread-out Bragg peak (SOBP) characteristics in proton therapy., Subjects and Methods: Proton beams with nominal energies of 70, 120 and 210 MeV were considered. The soft tissues and tissue equivalent materials implemented in this study are: 9-component soft tissue, 4-component soft tissue, adipose tissue, muscle (skeletal), lung tissue, breast tissue, A-150 tissue equivalent plastic, perspex and water. Each material was separately defined inside a 20 cm × 20 cm × 40 cm phantom. A multilayer phantom was evaluated as well. The effect of tissue composition on the relative dose in SOBP region (relative to the dose in SOBP region in water), range of SOBP, length of SOBP, and uniformity index of SOBP was evaluated., Results: Various soft tissues and tissue equivalent materials have shown different dose level in SOBPs, ranges of SOBPs, lengths of SOBPs and uniformity indices., Conclusions: Based on the obtained results, various soft tissues and tissue equivalent materials have quite different SOBP characteristics. Since in clinical practice with proton therapy, only the range of SOBP is corrected for various tissues, omission of the above effects may result in major discrepancies in proton beam radiotherapy. To improve treatment accuracy, it is necessary to introduce such effects in treatment planning in proton therapy.

Background: The assessment of RBE quantity in the treatment of cancer tumors with proton beams in treatment planning systems (TPS) is of high significance. Given the significance of the issue and the studies conducted in the literature, this quantity is fixed and is taken as equal to 1.1., Objective: The main objective of this study was to assess RBE quantity of proton beams and their variations in different depths of the tumor. This dependency makes RBE values used in TPS no longer be fixed as they depend on the depth of the tumor and therefore this dependency causes some changes in the physical dose profile., Materials and Methods: The energy spectrum of protons was measured at various depths of the tumor using proton beam simulations and well as the complete simulation of a cell to a pair of DNA bases through Monte Carlo GEANT4. The resulting energy spectrum was used to estimate the number of double-strand breaks generated in cells. Finally, RBE values were calculated in terms of the penetration depth in the tumor., Results and Conclusion: The simulation results show that the RBE value not fixed terms of the depth of the tumor and it differs from the clinical value of 1.1 at the end of the dose profile and this will lead to a non-uniform absorbed dose profile. Therefore, to create a uniform impact dose area, deep-finishing systems need to be designed by taking into account deep RBE values., Competing Interests: Conflict of interests: None

Aim: The purpose of this work was to estimate the dependency between the produced positron emitters and the proton dose distribution as well as the dependency between points of annihilation and the proton dose distribution., Background: One important feature of proton therapy is that, through the non-elastic nuclear interaction of protons with the target nuclei such as 12 C, 14 N and 16 O, it produces a small number of positron-emitting radioisotopes along the beam-path. These radioisotopes allow imaging the Bragg peak position which is related to the proton dose distribution by using positron emission tomography., Methods: In this study, the GEANT4 toolkit was applied to simulate a soft and bone tissue phantom in proton therapy to evaluate the positron emitter productions and the actual annihilation points of β + . Simulation was done by delivering pencil and spread-out Bragg peak (SOBP) proton beams., Results: The findings showed that ( 15 O, 11 C, 13 N) and ( 11 C, 15 O, 38 K, 30 P, 39 Ca, 13 N) are the most suitable positron emitters in the soft and bone tissue respectively. By increasing the proton energy, the distance between the peak of annihilation profile and Bragg peak is almost constant, but the distance between the Bragg peak position and positron annihilation point peak in bone tissue is smaller than that in the soft tissue. The peak of β + activity distribution becomes sharper at higher proton energies., Conclusions: There is a good relationship between the positions of positron annihilation profile and positron emitters radioactive decay. Also, GEANT4 is a powerful and suitable tool for simulation of nuclear interactions and positron emitters in tissues.

Background: In radiation therapy with ion beams, lateral distributions of absorbed dose in the tissue are important. Heavy ion therapy, such as carbon-ion therapy, is a novel technique of high-precision external radiotherapy which has advantages over proton therapy in terms of dose locality and biological effectiveness., Methods: In this study, we used Monte Carlo method-based Geant4 toolkit to simulate and calculate the effects of energy, shape and type of ion beams incident upon water on multiple scattering processes. Nuclear reactions have been taken into account in our calculation. A verification of this approach by comparing experimental data and Monte Carlo methods will be presented in an upcoming paper., Results: Increasing particle energies, the width of the Bragg curve becomes larger but with increasing mass of particles, the width of the Bragg curve decreases. This is one of the advantages of carbon-ion therapy to treat with proton. The transverse scattering of dose distribution is increased with energy at the end of heavy ion beam range. It can also be seen that the amount of the dose scattering for carbon-ion beam is less than that of proton beam, up to about 160mm depth in water., Conclusion: The distortion of Bragg peak profiles, due to lateral scattering of carbon-ion, is less than proton. Although carbon-ions are primarily scattered less than protons, the corresponding dose distributions, especially the lateral dose, are not much less.

Adenosine receptors (AR) play an important role in the regulation processes for body temperature and vigilance states. During our previous studies, we noticed that aminophylline (a non-selective, blood-brain-barrier penetrably AR antagonist) could attenuate the effects of YZG-330 [(2R,3S,4R,5R)-2-(hydroxymethyl-5-(6-(((R)-1-phenylpropyl)amino)-9H-purin-9-yl)tetrahydrofuran-3, 4-diol] on lowering the body temperature. Hereby, we focused ourselves on the character of thermal regulation effect of YZG-330 in mice and tried to specify the receptor subtype via giving typical adenosine receptor antagonists. The results showed that both of the magnitude and lasting time of the effect that YZG-330 played on decreasing body temperature are in a dose-dependent manner: within the next 3 hour after intragastric administration (ig) of 0.25, 1 or 4 mg . kg-1 YZG-330, the extreme values on body temperature decreasing were (1.2 ± 0.3) °C, (3.6 ± 0.4) °C (P<0.001) and (7.4±0.5) °C (P<0.001), separately; whereas the duration that body temperature below 34 °C were 0, (10±5) and (153±4) min, separately. Adenosine A1 receptor (A1R) antagonist (DPCPX) could effectively reverse YZG-330's effect on decreasing body temperature, with intraperitoneal administration of DPCPX (5 mg . kg-1) 20 min prior than YZG-330 (4 mg.kg-1, ig), the extreme value on body temperature decreasing was (3.5 ± 0.7) °C (P<0.001), the duration that body temperature below 34 °C was (8±6) min (P<0.001). However, adenosine A2a receptor antagonist, SCH-58261, did not show any influence on the effects of YZG-330 at all. Combined with the fact that 8-SPT (a non-selective, blood-brain-barrier impenetrably AR antagonist) did not reverse the effect of YZG-330, we come to the conclusion that central-adenosine A, receptor plays a significant role on the thermal regulation effect of YZG-330.

Aim: Evaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy., Background: Radiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak., Materials and Methods: A slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code., Results: By using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined., Conclusions: It was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy "leaked" from the head by secondary photons and neutrons to be around 1%.

Uveitis is one of the most important causes of blindness worldwide. Its etiology and pathogenesis are complicated and have not been well understood. The treatment for uveitis is predominantly based on steroids and immunosuppressants. However, systemic side effects limit their clinical application. With the advancement of molecular biology, some intravitreal implants and biologic agents have been used for the treatment of uveitis. Additionally, novel techniques such as gene therapy and RNA interference are being studied for using as uveitis therapy. This paper reviews recent advances in uveitis treatment.

Objective: To determine whether alpha lipoic acid (LA) can effectively protect lenses from hydrogen peroxide (H2O2)-induced cataract., Methods: Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2, 0.2 mM of H2O2 plus 0.5 mM, 1.0 mM, or 2.0 mM of LA for 24 h. Cataract was assessed using cross line grey scale measurement. Superoxide dismutase (SOD), glutathione (GSH-Px), lactate dehydrogenase (LDH), and malondialdehyde (MDA) activity or level in lens homogenates was measured. Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay., Results: A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens' epithelial cells, but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis. Furthermore, 0.2 mM of H2O2 significantly decreased SOD, GSH-Px, and LDH activity and significant increased MDA level in the lens, but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2. One mM of LA was found to be the most effective., Conclusions: LA can protect lens from H2O2-induced cataract. LA exerts protective effects through inhibition of lens' epithelial cell apoptosis and activation of anti-oxidative enzymes., (Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

Context: Antidepressant effects of various plants are generally attributed to their anti-inflammation and antioxidant activities. Cynanchum auriculatum Royle ex Wight (Asclepiadaceae) is a traditional medicinal plant in China and India used for immunological regulation, anti-inflammation, and antioxidant purposes. However knowledge about its antidepressant activity has been poorly investigated., Objective: To investigate the antidepressant activities of the total glycosides of C. auriculatum (TGC) and its CHCl₃/MeOH (10:1) fractions (TGC-D and TGC-E) in mice., Materials and Methods: TGC, TGC-D and TGC-E (20, 40 and 80 mg/kg) were intragastrically administered to mice twice a day for 5 days. The tail suspension test, forced swimming test, and locomotor activity test in mice were used to evaluate the effect of C. auriculatum. The inhibition of [³H]-serotonin reuptake in rat brain synaptosomes was detected to investigate their mechanism., Results: TGC, TGC-D and TGC-E (80 mg/kg) decreased the immobility time by 61.7, 64.5, and 61.9% in tail suspension test. TGC (80 mg/kg), TGC-D (80 mg/kg) and TGC-E (20 mg/kg) decreased the immobility time by 32.6, 47.3, and 48.7% in forced swimming test. TGC (80 mg/kg) and TGC-E (20 and 40 mg/kg) decreased the crossing distances by 28.8, 29.5, and 36.2% in locomotor activity test. TGC, TGC-D and TGC-E (10 mg/L) inhibited serotonin reuptake by 7.4, 4.5, and 71.1% in rat brain synaptosomes, and IC₅₀ value of TGC-E was 5.2 mg/L., Discussion and Conclusion: TGC, TGC-D and TGC-E have potential antidepressant activities. The antidepressive effect of TGC-E maybe attributed partly by the inhibiting effect on serotonin reuptake.

The introduction of selective laser trabeculoplasty (SLT) provided a new choice for the reduction of intraocular pressure (IOP) in eyes with open angle glaucoma (OAG) and ocular hypertension (OHT). SLT was demonstrated equally as effective as topical medical therapy and argon laser trabeculoplasty (ALT) to lower IOP. It is a potentially repeatable procedure because of the lack of coagulation damage to the trabecular meshwork (TM) and also effect in patients with previously failed ALT. SLT can be used to treat patients with OAG, pseudoexfoliation glaucoma, pigmentary glaucoma, normal-tension glaucoma, OHT, juvenile glaucoma, pseudophakic and aphakic glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or are noncompliant with medications, while not interfering with the success of future surgery. Its safety profiles include mild and transient inflammation, ocular pain and a small risk of moderate IOP elevations after the procedure. SLT is a safe and effective means of IOP reduction in eyes with OAG and OHT.

Descemet's membrane detachment (DMD) can be a potentially serious complication of intraocular surgery or ocular trauma. The cause is not very clear. We are trying to remind an awareness of the spectrum of DMD resulting from trabeculectomy by presenting a case of extensive DMD after trabeculectomy which was successfully repaired.

Purpose: Posterior capsular opacification (PCO) is caused partially by the migration of lens epithelial cells. To date, the mechanism of the migration is largely unknown. The purpose of this study was to investigate the effect of platelet-derived growth factor (PDGF)-triggered signaling pathways and its downstream effectors in the migration of lens epithelial cells., Methods: In vitro scratch-wound healing and transwell migration assays were used to measure the migration of lens epithelial cells. The activation of PDGFR beta, phosphatidylinositol 3-kinas (PI3K)/protein kinase B (Akt) and mitogen activation protein kinase (MAPK) pathways, the impact of PDGF stimulation on the expression of cell protrusion molecules, and the stabilization of beta-catenin were measured by western blotting. The translocation of beta-catenin was detected using indirect immunofluorescence., Results: PDGF was found to enhance cell migration, which depended on the PI3K/Akt pathway. The activation of the PI3K/Akt pathway by the PDGF/PDGFR beta axis induced the up regulation of cell protrusion molecules and stabilization and translocation of beta-catenin, contributing to enhanced cell migration., Conclusion: Data from this study directly linked the central PI3K/Akt pathway to lens epithelial cell migration and pointed to new avenues for therapeutic intervention in PCO.

Objective: To find a reasonable method for treating and preventing fibrinous membrane after intraocular lens (IOL) implantation by using diclofenac sodium or dionine topically., Methods: Forty-eight eyes of twenty-four adult pure bred New Zealand rabbits were divided into three groups randomly. Group A: rabits received diclofenac sodium eyedrops; Group B: rabbits received dionine eyedrops; Group C: controlled. All the eyes received lens extraction combined with posterior chamber intraocular lens implantation. The fibrinous membrane was observed after 1, 3, 5, 7, 14, 21 and 30 days postoperatively., Results: The fibrinous membran in Group A was less than that of Group B and Group C, (P < 0.05); the difference between group B and group C on fibrinous membrance was also statistically significant (P < 0.05)., Conclusion: The study suggests that both diclofenac sodium and the dionine eyedrops can treat fibrinous membrane after IOL implantation. The effect of diclofenac sodium is better than that of dionine.

Objective: The effects of diclofenac sodium(DFNa) combined with dionine in cases with fibrin exudation membrane on intraocular lens (IOL) were studied., Methods: Thirty-two eyes, derived from sixteen adult pure bred New Zealand rabbits, were divided at random into two groups after extracapsular lens extraction with posterior chamber IOL implantation: (1) rabbits received DFNa eyedrops combined with dionine eyedrops; (2) rabbits received Pred forte eyedrops. The sum of fibrinous exudation membrane on IOL was observed on 1, 3, 5, 7, 14, 21, 30d postoperation., Results: The fibrin exudations in the DFNa combined with dionine group is less than the pred forte group (P > 0.05)., Conclusion: DFNa combined with dionine is effective in treating fibrin exudation membrane after extracapsular lens extraction and IOL implantation, and it is more effective than the pred forte.