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Competing Interests: Declaration of competing interests There are no competing interests to disclose.

Significance: The primary role of platelets is to generate a thrombus by platelet activation. Platelet activation relies on calcium mobilization from the endoplasmic reticulum (ER). ER resident proteins, which are externalized upon platelet activation, are essential for the function of platelet surface receptors and intercellular interactions. Recent Advances: The platelet ER is a conduit for changes in cellular function in response to the extracellular milieu. ER homeostasis is maintained by an appropriate redox balance, regulated calcium stores and normal protein folding. Alterations in ER function and ER stress results in ER proteins externalizing to the cell surface, including members of the protein disulfide isomerase family (PDIs) and chaperones. Critical Issues: The platelet ER is central to platelet function, but our understanding of its regulation is incomplete. Previous studies have focused on the function of PDIs in the extracellular space, and much less on their intracellular role. How platelets maintain ER homeostasis and how they direct ER chaperone proteins to facilitate intercellular signalling is unknown. Future Directions: An understanding of ER functions in the platelet is essential as these may determine critical platelet activities such as secretion and adhesion. Studies are necessary to understand the redox reactions of PDIs in the intracellular versus extracellular space, as these differentially affect platelet function. An unresolved question is how platelet ER proteins control calcium release. Regulation of protein folding in the platelet and downstream pathways of ER stress require further evaluation. Targeting the platelet ER may have therapeutic application in metabolic and neoplastic disease.

Ethnopharmacological Relevance: Hepatocellular carcinoma (HCC) is among the most prevalent malignant tumors globally and represents a significant public health issue worldwide. Immune cell dysfunction is the crucial factor for the formation of immunosuppression microenvironment of HCC. Glehnia littoralis (A.Gray) F.Schmidt ex Miq. (Shashen) and Ophiopogon japonicus (Thunb.) Ker Gawl. (Maidong) are classic herb pair in traditional Chinese medicine (TCM) of nourishing Yin, and is widely applied in the treatment of HCC and possesses multiple immunomodulatory functions. However, the role of the Shashen-Maidong herb pair (SS-MD) for the management of HCC and the potential mechanisms has not been explicated., Aim of the Study: The purpose of the research is to investigate the potential mechanism of the SS-MD herb pair for the management of HCC., Materials and Methods: The known components of the SS-MD herb pair were preliminarily identified using UPLC-Q-Orbitrap-MS/MS. The active ingredients of SS-MD herb pair in treating HCC were screened by constructing herb-component-target network, and the key therapeutic targets were explored by constructing a protein-protein interaction (PPI) network. The binding affinity of the key targets and components were validated through molecular docking and molecular dynamics simulations. GO biological function and KEGG pathway analyses were operated to elucidate the potential mechanisms of the SS-MD herb pair for the management of HCC. And the mechanism was verified in the tumor bearing mice model and cell co-culture experiments., Results: Network pharmacology prediction revealed 39 active components and 138 targets of the SS-MD herb pair for the treatment of HCC. KEGG analysis mainly focused on Notch signaling pathway and Apoptosis signaling pathway. The targets were enriched in biological functions of lymphocyte effector function and lymphocyte apoptosis. In vivo and in vitro experiments proved that the SS-MD herb pair can improve the proportion of CD8 + T cells in the HCC immune microenvironment, regulate its subgroup distribution. SS-MD herb pair promoted CD8 + T cells to secrete IL-2, TNF-α, IFN-γ, Granzyme B and Perforin, and inhibited apoptosis by regulating Notch signaling pathway., Conclusions: This study identified the key components, targets, and signaling pathways of the SS-MD herb pair, confirm that SS-MD herb pair play an immunomodulatory role in treating HCC, provides theoretical support for the collaborative treatment of HCC with TCM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no competing interest.

Many real-world complex systems, when hitting a tipping point, undergo irreversible sudden shifts that can eventually take a great toll on humanity and the natural world, such as ecosystem collapses, disease outbreaks, etc. Previous work has adopted approximations to predict the tipping points, but due to the nature of nonlinearity, this may lead to unexpected errors in predicting real-world systems. Here we obtain the rigorous bounds of the tipping points for general nonlinear cooperative networks. Our results offer two rigorous criteria that determine the collapse and survival of such a system. These two criteria are decided by the combined effect of dynamical parameters and interaction topology.

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group ( n =863), FIT group ( n =1 723) and novel risk-adapted screening approach group ( n =1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group ( P <0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group ( P <0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant ( P >0.05). The colonoscopy resource load (95% CI ) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95% CI ) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.

Objective: To investigate the effect of caspase activity and apoptosis inhibitor 1 (CAAP1) on the proliferation, migration and invasion of hepatoma cell SMMC-7721., Methods: pcDNA3/ CAAP 1, the overexpression vector of CAAP 1, and pSilencer 2.1-U6 neo/shR- CAAP 1, the knockdown vector, were constructed and examined. The experiment included 4 groups of SMMC-7721 cells, pcDNA3/ CAAP 1 group, pcDNA3 control group, shR- CAAP 1 group and pSilencer control group. After the SMMC-7721 cells were cultured, the overexpression vector pcDNA3/ CAAP 1 (the pcDNA3/ CAAP 1 group), knockdown vector shR- CAAP 1 (the shR- CAAP 1 group) and their controls (pcDNA3 control group and pSilencer control group) were transfected into SMMC-7721 cells respectively, and the follow-up experiments were carried out 48 h later. The mRNA expression of CAAP 1 in each group was examined with qRT-PCR. The protein expression level of CAAP1 and cleaved Caspase-3 were checked with Western blot. The proliferation of cells was examined with CCK-8. The colony formation ability and the motility of cells in each group were assessed with colony formation assay and wound-healing assay, respectively. The migration and invasion of cells were examined with Transwell cell chamber and the apoptosis of cells was examined with flow cytometry. The data of 75 patients with low expression of CAAP 1 and 295 patients with high expression of CAAP 1 were downloaded from TCGA database and the data of 48 months follow-up were analyzed. Kaplan-Meier survival curve was used to compare the correlation between different levels of CAAP 1 expression and overall survival (OS) of hepatocellular carcinoma (HCC) patients., Results: Double enzyme digestion analysis showed that the overexpression vector pcDNA3/ CAAP 1 and knockdown vector shR- CAAP 1 were constructed successfully. qRT-PCR and Western blot results showed that pcDNA3/ CAAP 1 increased the mRNA and protein expression level of CAAP1 in SMMC-7721 cells (in comparison with the pcDNA3 control group, P <0.05), while shR- CAAP 1 decreased the mRNA and protein expression of CAAP1 (in comparison with the pSilencer control group, P <0.05). Compared with pcDNA3 control group, the proliferation, colony formation ability, motility, migration and invasion of SMMC-7721 cells in the pcDNA3/ CAAP 1 group were increased, while the apoptosis of SMMC-7721 cells was inhibited (all P <0.05). Compared with the pSilencer control group, the proliferation, colony formation ability, motility, migration and invasion ability of SMMC-7721 cells in the shR- CAAP 1 group decreased, while the apoptosis increased (all P <0.05). TCGA database analysis showed that HCC patients with low CAAP 1 expression had better OS than that of HCC patients with high CAAP 1 expression., Conclusion: CAAP1 can promote the proliferation, migration and invasion of SMMC-7721 cells while it inhibit their apoptosis., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: Since December 2019, there have been many cases of viral pneumonia of unknown causes in Wuhan City, Hubei Province. During the period of novel coronavirus, according to the observation of limited autopsy and biopsy pathological results, pulmonary interstitial fibrosis appeared in some pathological changes of lung. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia with unknown etiology and pathological changes limited to the lung. At present, there is still a lack of reevaluation of systematic evaluation of traditional Chinese medicine treatment IPF. Therefore, a systematic re-evaluation of the systematic evaluation of traditional Chinese medicine in the treatment of pulmonary fibrosis may help to understand the effective treatment scheme of traditional Chinese medicine in the treatment of pulmonary fibrosis and provide more reliable evidence for the first-line clinicians to treat novel coronavirus., Methods: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure [CNKI], WangFang Database, Chinese Biomedical Literature Database [CBM], and Chinese Scientific Journal Database [VIP]) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. We will consider SRs and meta-analysis of Traditional Chinese Medicine for the Treatment of pulmonary fibrosis. Two reviewers will identify relevant studies, and then assess the methodological quality by assessment of multiple systematic reviews-2 tool. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report checklist to assess the quality of reports included in the study. In order to better evaluate the systematic evaluation included in this research, risk of bias in systematic review tool is included in this research to evaluate the methodological quality. The quality of evidence of the included systematic reviews was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Primary outcomes include: Clinical total effective rate, curative effect of TCM symptoms, pulmonary function and blood gas analysis., Results: The results of this study will be published in a peer-reviewed journal., Conclusions: We expect to obtain reliable evidence from systematic analysis of traditional Chinese medicine treatment of pulmonary fibrosis in an available and useful document., Registration Number: INPLASY202060029.

Objective: To investigate the acceptance and attitude toward a novel fecal immunochemical test (FIT) in colorectal cancer screening among populations in China. Methods: From May 2018 to May 2019, 2 474 people aged 50-74 years were recruited from five provinces of China (Zhejiang, Anhui, Jiangsu, Hunan and Yunnan). The general demographic characteristics, acceptance of the new FIT technology and operational difficulties through the whole screening process were obtained through questionnaire survey. Multivariate logistic regression model was used to analyze the factors related to difficulties encountered in sampling stool, reading and uploading results. Results: The subjects were (60.0±6.4) years old, and female, high school of above educated, unemployed/retired/other, married and with medical insurance status of "new rural cooperative medical care (NRCMC)" accounted for 61.7% (1 526), 29.0%(718), 34.3% (849), 92.7% (2 293) and 31.3%(775), respectively. The population's acceptance of the FIT technology was 94.8%. In the process of FIT screening, the percentage of occurred difficulties in sampling stool, reading and uploading results were 33.1% (819), 46.4% (1 147) and 62.9% (1 557), respectively. The main difficulties were the uncertainty about whether the sampling operation was standard (28.0%), the inability to accurately judge the result displayed (32.5%) and the need for help without using a smartphone (44.2%). The results of multivariate logistic regression model analysis showed that people aged 65-74 years old and with medical insurance status of "NRCMC" were more likely to encounter difficulties in sampling, and those who were unemployed/retired/other and living with 3 or more family members were less likely to encounter difficulties in sampling. Those aged 65-74 years old, farmers or migrant workers, and those with "NRCMC" were more likely to encounter difficulties in readingresults, and those with 3 or more family members were less likely to encounter difficulties in reading result. Those with "NRCMC" were more likely to encounter difficulties in uploading results, and those with education level of high school or above, living with more than 3 family members were less likely to encounter difficulties in uploading results. Conclusion: The acceptance of the new FIT technology is relatively high among the subjects. Age, education level, occupation, number of family members living together and medical insurance status might be related to difficulties encountered in sampling stool, reading and uploading results, and it can be further strengthened in terms of the technology and characteristics of sub-populations.

A mathematical model considering the transmission of a partially coherent Gaussian Schell-model (GSM) beam in slant turbulence atmosphere of heterodyne detection was established. A closed-form expression of the weighting factor for the partially GSM beam at the receiving end was derived. The effect of the beam mode on the performance of the proposed detection system was theoretically investigated. The results show that the proportion of the fundamental mode and heterodyne efficiency can be optimized by controlling the waist radius of the signal and local oscillator beams. The inner scale of turbulence significantly affects the heterodyne efficiency and normalized M 2 . With a larger mode order, the proportion of the fundamental mode and heterodyne efficiency are lowered.

Objective To investigate the clinical value of serum tumor marker isocitrate dehydrogenase 1(IDH1)in the diagnosis of lung cancer. Methods The general data were collected in lung cancer patients and non-lung cancer patients.The serum level of IDH1 was detected by enzyme-linked immunosorbent assay to evaluate its clinical significance in diagnosing lung cancer. Results The serum IDH1 level was significantly higher in lung cancer patients than in non-lung cancer patients [(7.12±6.98)ng/ml vs. (2.09±1.83)ng/ml, t =11.540, P <0.001].The serum IDH1 level in patients with adenocarcinoma or squamous cell carcinoma was significantly higher than that in patients with small cell lung cancer [(7.91±7.26)ng/ml vs. (2.76±2.27)ng/ml, t =6.345, P <0.001].The sensitivity of IDH1 in detecting lung cancer,stage Ⅰ/Ⅱ lung cancer,and stage Ⅲ/Ⅳ lung cancer was 47.4%,49.1%,and 46.3%,respectively. Conclusions Serum IDH1 has high sensitivities and specificities in the diagnosis and differential diagnosis of non-small cell lung cancer(squamous cell carcinoma and adenocarcinoma)and small cell lung cancer as well as the auxiliary diagnosis of stage Ⅰ and Ⅱ lung cancer.It is a valuable marker for the auxiliary diagnosis of lung cancer.

Aeromonas veronii is a pathogen capable of infecting humans, livestock and aquatic animals, resulting in serious economic losses. In this study, two recombinant Lactobacillus casei expressing flagellin A (FlaA) of A. veronii , Lc-pPG-1-FlaA (surface-displayed) and Lc-pPG-2-FlaA (secretory) were constructed. The immune responses in fish administered with recombinant L. casei were evaluated. The two recombinant L. casei were orally administered to common carp, which stimulated high serum IgM and induced higher ACP, AKP, SOD and LYZ activity. Using qRT-PCR, the expression of IL-10, IL-8, IL-1β, TNF-α and IFN-γ in the tissue of fish immunized with recombinant L. casei was significantly ( p < 0.05) upregulated, which indicated that recombinant L. casei could activate the innate immune system to trigger the cell immune response and inflammatory response. Furthermore, recombinant L. casei was able to survive the intestinal environment and colonize in intestine mucosal. The study showed that after being challenged by A. veronii , fish administered with Lc-pPG-1-FlaA (70%) and Lc-pPG-2-FlaA (50%) had higher survival rates compared to Lc-pPG and PBS, indicating that recombinant L. casei might prevent A. veronii infection by activating the immune system to trigger immune responses. We demonstrated that flagellin as an antigen of vaccine, is acceptable for preventing A. veronii infection in fish. The recombinant L. casei expressing FlaA may be a novel mucosal vaccine for treating and controlling A. veronii .

The incidence of colorectal cancer (colorectal cancer, CRC) in China has increased in recent years, and its mortality rate has become one of the highest among all cancers. CRC also increasingly affects people's health and quality of life, and the workloads of medical doctors have further increased due to the lack of sufficient medical resources in China. The goal of this study was to construct an automated expert system using a deep learning technique to predict the probability of early stage CRC based on the patient's case report and the patient's attributes. Compared with previous prediction methods, which are either based on sophisticated examinations or have high computational complexity, this method is shown to provide valuable information such as suggesting potentially important early signs to assist in early diagnosis, early treatment and prevention of CRC, hence helping medical doctors reduce the workloads of endoscopies and other treatments.

GDP is a classic indicator of the extent of national economic development. Research based on the World Trade Network has found that a country's GDP depends largely on the products it exports. In order to increase the competitiveness of a country and further increase its GDP, a crucial issue is finding the right direction to upgrade the industry so that the country can enhance its competitiveness. The proximity indicator measures the similarity between products and can be used to predict the probability that a country will develop a new industry. On the other hand, the Fitness-Complexity algorithm can help to find the important products and developing countries. In this paper, we find that the maximum of the proximity between a certain product and a country's existing products is highly correlated with the probability that the country exports this new product in the next year. In addition, we find that the more products that are related to a certain product, the higher probability of the emergence of the new product. Finally, we combine the proximity indicator and the Fitness-Complexity algorithm and then attempt to provide a recommendation list of new products that can help developing countries to upgrade their industry. A few examples are given in the end.

Background: Sclerosing peritonitis (SP) is a rare but potentially fatal complication following orthotopic liver transplantation (OLT). The definitive surgical management is via a laparotomy peritonectomy and enterolysis procedure, but this carries risks particularly in the immunosuppressed transplant patient population. The natural history of SP is known from a handful of case reports and series, which mostly report de novo cases arising early on following OLT. The aim of this study was to identify all cases of de novo SP following OLT and the outcomes of management., Methods: Cases of SP post OLT were identified from the Australian National Liver Transplantation Unit (New South Wales) database of all 1393 adult patients., Results: Three cases of SP were diagnosed between 2 and over 9 years post-transplantation. Two patients proceeded to laparotomy and a peritonectomy and enterolysis procedure of the cocooned bowel. The third was managed conservatively due to a relatively indolent course and their medical co-morbidities., Conclusion: SP should be considered in the differential diagnosis in patients post OLT presenting with symptoms of bowel obstruction, even years following transplantation. Surgery may be required in order to achieve a satisfactory outcome in some cases., (© 2017 Royal Australasian College of Surgeons.)

Purpose: Recent developments in electronic technology are making it possible to home monitor the sensitivity of the central visual field using portable devices. We used simulations to investigate whether the higher test frequency afforded by home monitoring improves the early detection of rapid visual field loss in glaucoma and how any benefits might be affected by imperfect compliance or increased variability in the home-monitoring test., Design: Computer simulation, with parameter selection confirmed with a cohort study., Participants: A total of 43 patients with treated glaucoma (both open-angle and closed-angle), ocular hypertension or glaucoma suspects (mean age, 71 years; range, 37-89 years), were followed in the cohort study., Methods: We simulated series (n = 100 000) of visual fields for patients with stable glaucoma and patients with progressing glaucoma for 2 in-clinic (yearly and 6-monthly) and 3 home-monitoring (monthly, fortnightly, and weekly) schedules, each running over a 5-year period. Various percentages of home-monitored fields were omitted at random to simulate reduced compliance, and the variability of the home monitored fields also was manipulated. We used previously published variability characteristics for perimetry and confirmed their appropriateness for a home-monitoring device by measuring the device's retest variability at 2 months in a cohort of 43 patients. The criterion for flagging progression in our simulation was a significant slope of the ordinary least squares regression of a simulated patient's mean deviation (MD) data., Main Outcome Measures: The sensitivity for identifying rapid visual field loss (-2 decibels [dB]/year loss of MD)., Results: Although a sensitivity of 0.8 for rapid field loss was achieved after 2.5 years of 6-monthly testing in the clinic, weekly home monitoring achieved this by 0.9 years despite moderate test compliance of 63%. The improved performance of weekly home monitoring over 6-monthly clinical testing was retained even when home monitoring was assumed to produce more variable test results or be associated with low patient compliance., Conclusions: Detecting rapid visual field progression may be improved using a home-monitoring strategy, even when compliance is imperfect. The cost-benefit of such an approach is yet to be demonstrated, however., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the accuracy and efficiency of Visual Fields Easy (VFE), a free iPad app, for performing suprathreshold perimetric screening., Design: Prospective, cross-sectional validation study., Methods: We performed screening visual fields using a calibrated iPad 2 with the VFE application on 206 subjects (411 eyes): 210 normal (NL), 183 glaucoma (GL), and 18 diabetic retinopathy (DR) at Tilganga Institute of Ophthalmology, Kathmandu, Nepal. We correlated the results with a Humphrey Field Analyzer using 24-2 SITA Standard tests on 373 of these eyes (198 NL, 160 GL, 15 DR)., Results: The number of missed locations on the VFE correlated with mean deviation (MD, r = 0.79), pattern standard deviation (PSD, r = 0.60), and number of locations that were worse than the 95% confidence limits for total deviation (r = 0.51) and pattern deviation (r = 0.68) using SITA Standard. iPad suprathreshold perimetry was able to detect most visual field deficits with moderate (MD of -6 to -12 dB) and advanced (MD worse than -12 dB) loss, but had greater difficulty in detecting early (MD better than -6 dB) loss, primarily owing to an elevated false-positive response rate. The average time to perform the Visual Fields Easy test was 3 minutes, 18 seconds (standard deviation = 16.88 seconds)., Discussion: The Visual Fields Easy test procedure is a portable, fast, effective procedure for detecting moderate and advanced visual field loss. Improvements are currently underway to monitor eye and head tracking during testing, reduce testing time, improve performance, and eliminate the need to touch the video screen surface., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To determine the correlation between the perimetric outcomes from perimetry software Melbourne Rapid Fields (MRF) run on an Apple iPad tablet and those from the Humphrey Field Analyzer (HFA)., Methods: The MRF software was designed with features including variable fixation and fast thresholding using Bayes logic. Here, we report a cross-sectional study on 90 eyes from 90 participants: 12 had normal optic nerves and 78 had glaucoma with various degrees of visual field loss (41 mild and 37 moderate-severe). Exclusion criteria were patients with worse than 20/40 vision or recent intraocular surgery. The visual field outcomes of MRF were compared against those returned from the HFA 24-2 SITA standard. Participants were tested twice on the MRF to establish test-retest repeatability., Results: The test durations were shorter on MRF than HFA (5.7 ± 0.1 vs. 6.3 ± 0.1 minutes, P < 0.001). MRF showed a high level of concordance in its outcomes with HFA (intraclass coefficient [ICC] = 0.93 for mean defect [MD] and 0.86 for pattern deviation [PD]) although the MRF tended to give a less negative MD (1.4 dB bias) compared with the HFA. MRF also showed levels of test-retest reliability comparable to HFA (ICC = 0.93 for MD and 0.89 for PD, 95% limits of agreement -4.5 to 4.3 dB)., Conclusion: The perimetry results from the MRF have a strong correlation to the HFA outcomes. MRF also has test-retest reliability comparable to HFA., Translational Relevance: Portable tablet perimetry may allow accurate assessment of visual field when standard perimetry machines are unavailable or unsuitable.

Objective: To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice., Methods: Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected., Results: Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P < 0.01); levels of TC, TG, LDL-C increased, and HDL-C level decreased in 12- and 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01); the proportion of Mo increased in 4-week-old apoE(-/-) mice (P < 0.05); proportions of Mo and Ly6c(hi) increased in 8-week-old apoE(-/-) mice (P < 0.05). Compared with the blank control group, levels of TC, TG, and LDL-C, proportions of Mo and Ly6c(hi) increased (P < 0.01, P < 0.05), but HDL-C level decreased (P <0. 01) in the control group after intervention. Compared with the control group, body weight gained less in the Western medicine group and the Chinese medicine group (P < 0.05); the proportion of Ly6c(hi) subtype decreased in the Chinese medicine group (P < 0.05)., Conclusions: In development process blood lipids levels in apoE(-/-) mice are not only associated with age. Blood lipids levels induced growth changes in natural immune system are also correlated with age. In early stage of lipids development HJD intervention could correct this special immune disorder in apoE(-/-) mice.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To determine whether monoscopic vs stereoscopic viewing impacts evaluation of optic disc photographs for glaucoma diagnosis in an expert population., Design: Prospective observational study., Methods: Twenty pairs of high-quality monoscopic and stereoscopic photographs of similar size and magnification (ie, 40 images), were selected to demonstrate a range of optic disc features from a total of 197 eyes of 197 patients with glaucoma and normal subjects recruited from a tertiary clinic. These were presented in randomized order via an interactive platform (http://stereo.gone-project.com/). Participants assessed 9 topographic features and estimated glaucoma likelihood for each photograph. Main outcome measures were intra- and inter-observer agreement., Results: There was good intra-observer agreement between monoscopic and stereoscopic assessments of glaucoma likelihood (κw = 0.56). There was also good to substantial agreement for peripapillary atrophy (κw = 0.65), cup shape (κw = 0.65), retinal nerve fiber layer loss (κw = 0.69), vertical cup-to-disc ratio (κw = 0.58), and disc shape (κw = 0.57). However, intra-observer agreement was only fair to moderate for disc tilt, cup depth, and disc size (κw = 0.46-0.49). Inter-observer agreement for glaucoma likelihood in monoscopic photographs (κw = 0.61, 95% confidence interval [CI] = 0.55-0.67) was substantial and not lower than in stereoscopic photographs (κw = 0.59, CI = 0.54-0.65). Monoscopic photographs did not lead to lower levels of inter-observer agreement compared to stereoscopic photographs in the assessment of any optic disc characteristics, for example disc size (mono κw = 0.65, stereo κw = 0.52) and cup-to-disc ratio (mono κw = 0.72, stereo κw = 0.62)., Conclusions: For expert observers in the evaluation of optic disc photographs for glaucoma likelihood, monoscopic optic disc photographs did not appear to represent a significant disadvantage compared to stereoscopic photographs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Importance: Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire., Objectives: To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood., Design, Setting, and Participants: This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010., Interventions: A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood., Main Outcomes and Measures: Agreement (κ and weighted κ) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood., Results: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1% (1.6%) and 23.8% (1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0% (1.2%) and 8.9% (1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs., Conclusions and Relevance: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2.

Advancing age is a major risk factor for many neurodegenerative diseases but the underlying pathophysiology is not clear. We hypothesize that aging impairs the ability of neurons in the central nervous system to recover functionally after injury. To test this in retinal ganglion cells in vivo, we developed an optic nerve "stress test" which monitors the functional capacity of the optic nerve and retina, during and after a subischemic injury induced by intraocular pressure elevation. We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to the potential benefits of therapies that target mitochondria for the protection of the aging retina and optic nerve against injury., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Five propionic acid ionic liquids (PrAILs) [C(n)mim][Pro] (n = 2-6) (1-alkyl-3-methylimidazolium propionate) have been prepared by the neutralization method and characterized by (1)H NMR spectroscopy and differential scanning calorimetry (DSC). Their density, ρ, surface tension, γ, and refractive index, n(D), were measured at (298.15 ± 0.05) K, and the experimental values of parachor for the PrAILs were calculated. Using the parachor values of [C(n)mim](+) obtained by Guan et al., the anionic parachor values of [C(n)mim][Pro] (n = 2-6), [C(2)mim][RBF(3)] (R = N-C(n)H(2n+1) (n = 1-5)), [C(n)mim][Gly] (n = 2-6), and [C(n)mim][PF(3)(CF(2)CF(3))(3)] (n = 1-6) were determined. Then, the parachor, surface tension, and refractive index of the ILs investigated in this work were estimated. The estimated values correlate quite well with the corresponding experimental values.

Purpose: Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG., Methods: Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15)., Results: POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort., Conclusions: POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Mouse models that accumulate high levels of mitochondrial DNA (mtDNA) mutations owing to impairments in mitochondrial polymerase γ (PolG) proofreading function have been shown to develop phenotypes consistent with accelerated aging. As increase in mtDNA mutations and aging are risk factors for neurodegenerative diseases, we sought to determine whether increase in mtDNA mutations renders neurons more vulnerable to injury. We therefore examined the in vivo functional activity of retinal neurons and their ability to cope with stress in transgenic mice harboring a neural-targeted mutant PolG gene with an impaired proofreading capability (Kasahara, et al. (2006) Mol Psychiatry11(6):577-93, 523). We confirmed that the retina of these transgenic mice have increased mtDNA deletions and point mutations and decreased expression of mitochondrial oxidative phosphorylation enzymes. Associated with these changes, the PolG transgenic mice demonstrated accelerated age-related loss in retinal function as measured by dark-adapted electroretinogram, particularly in the inner and middle retina. Furthermore, the retinal ganglion cell-dominant inner retinal function in PolG transgenic mice showed greater vulnerability to injury induced by raised intraocular pressure, an insult known to produce mechanical, metabolic, and oxidative stress in the retina. These findings indicate that an accumulation of mtDNA mutations is associated with impairment in neural function and reduced capacity of neurons to resist external stress in vivo, suggesting a potential mechanism whereby aging central nervous system can become more vulnerable to neurodegeneration., (© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Purpose: The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination., Methods: Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction., Results: Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology., Conclusions: Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.

Background: Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment., Design: Prospective internet-based observational study., Participants: Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries., Methods: Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood., Main Outcome Measures: Inter-observer agreement using kappa (κ) or weighted kappa (κ(w) )., Results: There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κ(w) = 0.63). Inter-observer agreement was high for haemorrhage (κ= 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κ(w) = 0.59-0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood., Conclusions: This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination., (© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.)

Objective: : Video-assisted thoracoscopic (VATS) thymectomy has been practiced in Australia for nearly two decades. Our aim was to assess the complete stable remission and asymptomatic disease rates after VATS thymectomy in nonthymomatous myasthenia gravis. There remains doubt that minimally invasive techniques achieve equal remission rates to open maximal operations. Therefore, we report our outcomes using the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification and Kaplan-Meier analysis and compare the results to the literature., Methods: : A retrospective analysis of 78 consecutive patients undergoing right VATS thymectomy between April 1994 and March 2007 at two Thoracic Surgery Units in Melbourne, Australia, was undertaken. Patients with thymoma were excluded. Therefore, 57 patients were followed-up for a minimum of 12 months to apply the MGFA Clinical Classification. VATS thymectomy was performed by a three-port right side technique., Results: : The complete stable remission rate was 15% at 3 years and 28% at 5 years. The asymptomatic disease rate was 59% at 5 years. Median follow-up was 32 months. No prognostic factors for remission were identified. The overall morbidity rate was 14% (8/57)., Conclusions: : Right VATS thymectomy achieves comparable remission and asymptomatic disease rates to other minimally invasive and open techniques when compared with studies using either MGFA or older criteria.

Background/aims: To evaluate the association between demographical features, serum ALT and HBV DNA and the prevalence of significant fibrosis and inflammation on liver biopsy in patients with chronic hepatitis B., Methods: In this cross-sectional study of patients on St Vincent's Hospital HBV database, patients were classified into three groups on the basis of HBeAg status and HBV DNA level and the prevalence of significant (F2/3/4) fibrosis and (A2/3) inflammation in each group was established. Patients were also divided into HBeAg-positive and -negative groups and examined for the prevalence of significant fibrosis/inflammation in the strata of HBV DNA and ALT. Predictors of significant fibrosis and inflammation in HBeAg-positive and -negative patients were examined by logistic regression., Results: Three hundred and ninety four patients (HBeAg positive=198; HBeAg negative=196) with liver biopsy were identified. Fifty-eight percent of HBeAg-negative patients with HBV DNA >25,000 IU/ml had F2/3/4 fibrosis. HBV DNA and F2/3/4 were positively correlated in HBeAg-negative patients [odds ratio (OR) 1.42, P=0.001] but inversely correlated in HBeAg-positive patients (OR 0.71, P=0.03). HBV DNA was an independent predictor of significant fibrosis in HBeAg negative (P=0.03) but not HBeAg-positive patients. In HBeAg-positive patients, age was the only predictor of significant fibrosis (P=0.001) and ALT the only predictor of significant inflammation (P=0.003). In the whole cohort there was a close positive association between inflammation and fibrosis., Conclusion: Increasing levels of HBV DNA are associated with increasing prevalence of significant fibrosis only in patients with HBeAg-negative CHB.

Low-temperature heat capacities of 2-pyrazinecarboxylic acid (C5H4N2O2)(s) were measured by a precision automated adiabatic calorimeter over the temperature range from 78 to 400 K. A polynomial equation of heat capacities as a function of temperature was fitted by least squares method. Based on the fitted polynomial, the smoothed heat capacities and thermodynamic functions of the compound relative to the standard reference temperature 298.15 K were calculated and tabulated at 10 K intervals. The constant-volume energy of combustion of the compound at T = 298.15 K was measured by a precision rotating-bomb combustion calorimeter to be ΔcU = -(17839.40 ± 7.40) J g-1. The standard molar enthalpy of combustion of the compound was determined to be ΔcH0m = -(2211.39 ± 0.92) KJ mol-1, according to the definition of combustion enthalpy. Finally, the standard molar enthalpy of formation of the compound was calculated to be ΔfH0m = -(327.82 ± 1.13) kJ mol-1 in accordance with Hess law.

Purpose: To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice., Methods: IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure-function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (-4.54, -2.23, and 0.34 log cd x s x m(-2)) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike., Results: The pSTR was most sensitive to IOP elevation with 50% amplitude loss (mu) at 41 mm Hg (mu, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR (-30% +/- 6%, P < 0.001) and OP (-27% +/- 2%, P < 0.001) amplitudes were reduced, whereas other components were unaffected., Conclusions: The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP amplitude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike.

During physiological processes molecules undergo chemical changes involving reducing and oxidizing reactions. A molecule with an unpaired electron can combine with a molecule capable of donating an electron. The donation of an electron is termed as oxidation whereas the gaining of an electron is called reduction. Reduction and oxidation can render the reduced molecule unstable and make it free to react with other molecules to cause damage to cellular and sub-cellular components such as membranes, proteins and DNA. In this paper, we have discussed the formation of reactive oxidant species originating from a variety of sources such as nitric oxide (NO) synthase (NOS), xanthine oxidases (XO), the cyclooxygenases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase isoforms and metal-catalysed reactions. In addition, we present a treatise on the physiological defences such as specialized enzymes and antioxidants that maintain reduction-oxidation (redox) balance. We have also given an account of how enzymes and antioxidants can be exhausted by the excessive production of reactive oxidant species (ROS) resulting in oxidative stress/nitrosative stress, a process that is an important mediator of cell damage. Important aspects of redox imbalance that triggers the activity of a number of signalling pathways including transcription factors activity, a process that is ubiquitous in cardiovascular disease related to ischemia/reperfusion injury have also been presented.

Optical channel waveguides in Nd/Ce codoped YAG laser crystal have been fabricated by using mask-assisted carbon ion implantation. The measured waveguide mode distributions were in good agreement with the calculated modal profiles, which implies the feasibility of designable devices. After thermal annealing treatment at 260 degrees C for 30 min in air, the propagation loss of the waveguide was reduced down to approximately 2 dB/cm at a wavelength of 632.8 nm. The microluminescence spectra of the waveguides show that the fluorescence properties of both Ce and Nd ions (including the energy transfer between them) are not significantly affected by the waveguide formation processing, which indicates a fairly good potential for further laser actions in a compact device.

Horner syndrome is an uncommon but important clinical entity, representing interruption of the sympathetic pathway to the eye and face. Horner syndrome is almost always diagnosed clinically, though pharmacological testing can be used to confirm the diagnosis. Imaging modalities such as PET, CT and MRI are important components of work-up for patients presenting with acquired Horner syndrome. Our patient's presentation with Horner syndrome unmasked the causative superior sulcus squamous cell carcinoma and a coincidental lower lobe adenocarcinoma. Successful radical treatment of these cancers resulted in complete resolution of the syndrome and disease-free survival at 18 months. We review the anatomy and pathophysiology underlying this and other causes of Horner syndrome.