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In this paper, the solutions of the matrix equation are discussed by employing the Hermite matrix, and some new results are gained. The necessary and sufficient conditions of having their Hermite matrix solution for the matrix equation XAX = A and X* AX= A and the general solutions have been also obtained. In addition, the conditions in the theorem of Yang Changlan and Wang Longbo's paper are weakened, and the results obtained by Jameson and Yang Changlan etc. are generalized. [ABSTRACT FROM AUTHOR]

Abstract: Zirconium diborides (ZrB2) porous ceramics were synthesized by the Spark Plasma Sintering-Reactive Synthesis (SPS–RS) technique using ZrO2 and B4C as precursors which undergo solid state reaction that lead to pore formation. Phase analysis of the products indicated that the reaction started between 1200°C and 1300°C and was carried out at 1600°C within 10min under SPS conditions, which was consistent with the thermodynamic calculations. The as-prepared ZrB2 porous ceramics had a relatively smaller crystallite size (~1μm), a lower oxygen content (~1.04wt.%) and a relative density of 29.9%. The oxygen impurities decreased with the sintering temperature and holding time. In addition, the measured results showed that the reaction was carried out within 10min holding time at the temperature of 1600°C and the synthesized ZrB2 products had high purity in comparison to commercial ZrB2 powder product. [Copyright &y& Elsevier]

Abstract: In this study, various nanoscale metal oxide catalysts, such as CeO2, TiO2, Fe2O3, Co3O4, and SiO2, were added to the LiBH4/2LiNH2/MgH2 system by using high-energy ball milling. Temperature programmed desorption and MS results showed that the Li–Mg–B–N–H/oxide mixtures were able to dehydrogenate at much lower temperatures. The order of the catalytic effect of the studied oxides was Fe2O3 >Co3O4 >CeO2 >TiO2 >SiO2. The onset dehydrogenation temperature was below 70°C for the samples doped with Fe2O3 and Co3O4 with 10wt.%. More than 5.4wt.% hydrogen was released at 140°C. X-ray diffraction indicated that the addition of metal oxides inhibited the formation of Mg(NH2)2 during ball milling processes. It is thought that the changing of the ball milling products results from the interaction of oxide ions in metal oxide catalysts with hydrogen atoms in MgH2. The catalytic effect depends on the activation capability of oxygen species in metal oxides on hydrogen atoms in hydrides. [Copyright &y& Elsevier]

This paper uses two game-theory models, where monetary policy is first ineffective and then effective, to illustrate a delegation scheme that makes consistent policy optimal and controllable. The delegation scheme produces the minimization of both the social and the central bank loss functions. Minimizing the social loss function generates optimality conditions. Minimizing the central bank loss function produces controllability conditions. Optimality conditions depend on specific models, and controllability conditions do not. We propose a concept of consistent targets, which refer to the targets that satisfy both optimality and controllability conditions. Consistent policy proves optimal and controllable in both example models when the government delegates consistent targets to the central bank. [ABSTRACT FROM AUTHOR]

Pure YB4 powder was synthesized via the reaction of Y2 O3 with B4 C under a vacuum pressure within the range of 20-50 Pa using spark plasma sintering ( SPS) route. The effect of temperature and the molar ratio of the starting materials was studied. The role of the YBO3, an intermediate product, in the synthesis of YB4 was investigated. For preparation of high purity YB4, the molar proportion of B4 C to Y2 O3 should not be higher than the stoichiometric ratio (15/7). YBO3 can be removed through decomposing to Y2 O3 and B2 O3 or reacting with B4 C to form YB4 and B2 O3 at a temperature above 1650°C. The little residual impurities, such as Y2 O3 and YBO3, can be removed by hydrochloric acid washing. Thus, a high purity YB4 powder has been synthesized. The oxygen content of the obtained YB4 is about 0.007% and the particle size is in the range of 3-10 μm. [ABSTRACT FROM AUTHOR]

Prcis: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae., Purpose: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract., Patients and Methods: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications., Results: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044)., Conclusions: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to assess the current status of early enteral nutrition (EN) support among patients diagnosed with acute pancreatitis (AP) and analyze the factors influencing its duration. The findings aimed to provide guidance for the development of tailored EN support protocols for pancreatitis patients., Methods: A convenience sampling method was employed, and 51 patients diagnosed with acute pancreatitis (AP) were enrolled from the Gastroenterology Department of Zhoushan Hospital between May 2020 and June 2021. Data analysis included the categorization of patients based on their early enteral nutrition (EN) support duration, followed by thorough statistical analysis, including logistic regression, to identify the factors impacting EN duration., Results: The mean duration of early EN support among AP patients was (93.57 ± 43.29) hours. A mere 13.73% of patients initiated EN within 48 hours of admission. Upon categorizing patients by the median duration of EN support, multiple logistic regression analysis revealed several significant risk factors influencing the duration of EN in AP patients, including patient age, underlying medical conditions, severity of pancreatitis, nutritional status, and blood lipase levels (P < .05)., Conclusion: The study highlights the significant influence of disease severity and patients' functional status on the duration of early EN support in AP cases. It emphasizes the importance of a comprehensive patient assessment by medical professionals to determine the optimal timing for initiating EN support.

Background: Although moderate weight loss improves outcomes of type 2 diabetes mellitus (T2DM) in young and middle-aged adults, there is a lack of high-quality evidence to support the strong relationship between obesity and T2DM in older people. This study aims to investigate whether the association of obesity with T2DM changes with aging., Methods: In this cross-sectional study, we recruited 63,180 Chinses and US subjects from 3 datasets. Subjects were divided into young & middle-aged (≤59 years), young-old (60-75 years), and old-old (≥75 years). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for the association between obesity and T2DM, stratified by common confounders. A sliding-window based algorithm and restricted cubic splines were used to smoothly estimate the changes with aging., Results: The OR (95% CI) for the associations between general obesity and T2DM were decreased from the young & middle-aged group (OR, 5.91; 95% CI, 5.33-6.56) to the young-old group (OR, 3.98; 95% CI, 3.56-4.45) and then to the old-old group (OR, 3.06; 95% CI, 2.57-3.66). The trend for this reduced association with aging persisted after stratification by obesity type, region, gender, recruiting time, hypertension, and hyperlipidemia in both Chinese and Americans. We also identified a weakened gender disparity for this association between the young & middle-aged subjects (P for disparity < 0.001) and the old-old group (P for disparity = ~ 0.36)., Conclusions: The obesity-T2DM association is clearly reduced with aging, which indicates that the elderly may gain fewer potential benefits in weight lose than the younger patients. Considering this attenuated association, as well as the increased incidence of geriatric syndrome in the elderly, clinicians should comprehensively balance the benefits and side effects of weight loss in geriatric T2DM interventions., (© 2022. The Author(s).)

Retinal ganglion cells (RGCs) axons are the signal carriers of visual information between retina and brain. Therefore, they play one of the important roles affected in many optic neurodegenerative diseases like glaucoma. Among the genetic risks associated with glaucoma, the E50K mutation in the Optineurin (OPTN) gene are known to result in glaucoma in the absence of increased intraocular pressure (IOP), whereas the relevant pathological mechanism and neurological issues remain to be further investigated. In this study, the OPTN (E50K) mutant mouse model was established through CRISPR/Cas9-mediated genome editing, and aging-related RGCs loss and the visual dysfunction were identified. In E50K mice 16 months old, the axonal transport decreased comparing to wild-type (WT) mice at the same age. Furthermore, results of electron microscopy demonstrated significant morphological anomaly of mitochondria in RGCs axons of young E50K mice 3 months old, and these changes were aggravated with age. These indicated that the damaged mitochondria-associated dysfunction of RGCs axon should play an etiological role in glaucoma as an age-related outcome of OPTN (E50K) mutation. The findings of this study have potential implications for the targeted prevention and treatment of NTG., (© 2022. The Author(s).)

Human longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer's disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1 + and Sca-1 - cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1 + and Sca-1 - chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1 + cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1 + cells from young healthy mice had greater paracrine trophic effects than Sca-1 - cells and Sca-1 + cells from young OPTN E50K mice. In addition, Sca-1 + chimaeras demonstrated better visual functions than Sca-1 - chimaeras and untreated OPTN E50K mice. More Sca-1 + cells than Sca-1 - cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1 + cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.

The glaucoma-associated E50K mutation in optineurin (OPTN) is known to affect autophagy and cause the apoptosis of retinal ganglion cells (RGCs), but the pathogenic mechanism remains unclear. In this study, we investigated whether the OPTN (E50K) mutation caused TDP-43 aggregation by disrupting autophagy in vivo and in vitro. OPTN (E50K) mutant mice were generated and analysed for genotype and phenotype. Adeno-associated virus type 2 vectors containing either GFP only, GFP-tagged wild-type OPTN or GFP-tagged E50K-mutated OPTN were used to transfect R28 cells. Loss of RGCs decreased retinal thickness and visual impairment were observed in OPTN (E50K) mice compared with WT mice. Moreover, overexpression of E50K OPTN induced R28 cell apoptosis. Increased p62/SQSTM1 and LC3-II levels indicated that autophagic flux was inhibited and contributed to TDP-43 aggregation in vivo and in vitro. We found that rapamycin effectively reduced the aggregation of TDP-43 in OPTN (E50K) mice and decreased the protein levels of p62/SQSTM1 and the autophagic marker LC3-II. Moreover, rapamycin increased the RGC number and visual function of E50K mice. In addition, we also observed increased cytoplasmic TDP-43 in the spinal cord and motor dysfunction in 24-month-old OPTN (E50K) mice, indicating that TDP-43 accumulation may be the common pathological mechanism of glaucoma and amyotrophic lateral sclerosis (ALS). In conclusion, the disruption of autophagy by OPTN (E50K) affected the degradation of TDP-43 and may play an important role in OPTN (E50K)-mediated glaucomatous retinal neurodegeneration.

Patients with type-2 diabetes mellitus (T2DM) display chronic low-grade inflammation induced by activation of the innate immune system. Toll-like receptor (TLR)4 is a pattern recognition receptor that plays a vital part in activation of the innate immune system. Results from animal and computer-simulation studies have demonstrated that targeting TLR4 to block the TLR4-nuclear factor-kappa B (NF-κB) pathway reduces the inflammatory response and complications associated with T2DM. Therefore, TLR4-targeted therapy has broad prospects. Here, we reviewed the role of TLR4 in inflammation during chronic hyperglycemia in T2DM and its therapeutic prospects., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Wang et al.)

Background: Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population., Methods: We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m 2 ) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia , obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia -obesity associations., Results: The median abundance of Akkermansia was 0.08% (interquartile range: 0.006-0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk ( P  = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94-1.39), 0.94 (0.77-1.15), 0.70 (0.56-0.85) and 0.79 (0.64-0.96) after adjusting for age and sex ( P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03-0.62) and 0.77 (0.64-0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging., Conclusion: High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Branched-chain amino acids (BCAAs) and telomere length are biologically associated with healthy aging. However, the association between them and their interaction on frailty remain unclear in humans. Here, a cross-sectional study based on residents from Guangxi longevity county was conducted to investigate the association of serum BCAAs, peripheral leukocyte telomere length (LTL) and frailty. A total of 1,034 subjects aged 20 to 110 years were recruited in the study. The real-time qPCR method and a targeted metabolomics approach based on isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) method were used for measurement of LTL and BCAAs, respectively. A frailty score defined as the proportion of accumulated deficits based on 24 aging-related items was used assess the health status of elderly subjects. First, we found that a higher concentration of BCAAs was significantly associated with longer LTL only in middle-aged subjects, independent of age and BMI (P < 0.05). In the oldest-old subjects, we identified a significantly inverse association between BCAAs and frailty score (P < 0.001), even after adjustment for age and BMI (P < 0.05). Additionally, we recognized a statistically significant synergetic interaction between BCAAs and LTL on frailty score in the oldest-old subjects by the general linear model (P = 0.042), although we did not find any significant association between LTL and frailty score. In summary, our findings suggest a potentially protective effect of circulating BCAAs on LTL and frailty based on the subjects from longevity county in East Asia and indicate a potential synergetic interaction between BCAAs and LTL in healthy aging.

Human longevity involves genetic, nutritional, environmental and many other factors playing a key role in healthy aging. Previous studies have shown that mineral metabolism and homeostasis are associated with lifespan extension. However, the majority of them have focused on a limited number of elements and ignored the complex relationship between them. In this study, we carried out a network-based approach to investigate the urinary ionome of nonagenarians and centenarians (longevity group) when compared with their biologically unrelated and younger family members (control group) from a Han Chinese population. Several differentially changed elements were identified, almost all of which showed an elevated level in the longevity group. Correlation analysis of the ionome revealed significant element-element interactions in each group. We then divided each group into distinct subgroups according to age ranges, and built the elemental correlation network for each of them. Significant elemental correlations and correlation changes involving all examined elements were identified within or between different subgroups, implying a highly dynamic and complex crosstalk among the elements during human life. Finally, more similar elemental patterns were observed between extremely old and middle-aged people. Overall, our data reveal new relationship between urinary minerals and human longevity, which may extend our understanding of the mechanism of healthy aging., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: FAT4 functions as a tumor suppressor, and previous findings have demonstrated that FAT4 can inhibit the epithelial-to-mesenchymal transition (EMT) and the proliferation of gastric cancer cells. However, few studies have investigated the role of FAT4 in the development of colorectal cancer (CRC). The current study aimed to detect the role of FAT4 in the invasion, migration, proliferation and autophagy of CRC and elucidate the probable molecular mechanisms through which FAT4 interacts with these processes., Methods: Transwell invasion assays, MTT assays, transmission electron microscopy, immunohistochemistry and western blotting were performed to evaluate the migration, invasion, proliferation and autophagy abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through a western blotting analysis. In addition, the function of FAT4 in vivo was assessed using a tumor xenograft model., Results: FAT4 expression in CRC tissues was weaker than that in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of FAT4 on autophagy and the EMT were partially attributed to the PI3K-AKT signaling pathway. The results in vivo also showed that FAT4 modulated CRC tumorigenesis., Conclusion: FAT4 can regulate the activity of PI3K to promote autophagy and inhibit the EMT in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3β signaling pathways.

Aims: β-Adrenergic receptors (ADRBs) play a pivotal role in cardiovascular disease. Recently, genetic polymorphisms of ADRB1 and ADRB2 have been suggested to be associated with cardiovascular events and all-cause mortality in coronary artery disease (CAD) patients, but the results of relevant studies are inconsistent and controversial. Therefore, we performed a meta-analysis to investigate the association between ADRB1 and ADRB2 polymorphisms with cardiovascular events and all-cause mortality in CAD patients., Materials and Methods: The PubMed, Ovid, EMBASE, Cochrane, and CINAHL databases were searched for eligible studies published before April 2018. A total of 5495 patients from eight studies were included in our meta-analysis., Results: We found that CAD patients harboring the ADRB2 rs1042714 Glu27 allele exhibited a positive association with cardiovascular events (risk ratio [RR] = 1.31, 95% confidence interval [CI]: 1.08-1.58, p = 0.006), but not with all-cause mortality (RR = 0.97, 95% CI: 0.70-1.35, p = 0.859), compared with patients who were Gln27 homozygotes. No other significant associations were observed between ADRB1 (rs1801252, rs1801253), ADRB2 (rs1042713, rs1800888) polymorphisms and cardiovascular events or all-cause mortality in CAD patients., Conclusion: This study suggests that the identified ADRB2 polymorphism could influence the outcomes of CAD patients, showing important clinical value.

An E50K substitution in the transcription factor optineurin (OPTN) induces primary open-angle glaucoma (POAG). To explore the potential role of microRNAs (miRNAs) in E50K OPTN-induced POAG, miRNA expression profiling was performed on retinal samples from OPTN (E50K) transgenic and wild-type mice. The retinas were collected from 30 transgenic and 30 wild-type mice, and miRNA expression was evaluated using a genome-wide miRNA microarray. miRNAs that were differentially expressed in retinal samples from OPTN (E50K) transgenic mice were identified and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additional gene ontology and signaling pathway analyses were performed using bioinformatics tools. A total of 48 miRNAs exhibited increased or decreased expression in the retinas from OPTN (E50K) transgenic mice when compared with the expression in the retinas from wild-type mice. A total of 5 miRNAs with increased expression in OPTN (E50K) transgenic mice could be grouped into one cluster as they belong to the miR-8 family and may act as regulators in the development of POAG in OPTN (E50K) transgenic mice. RT-qPCR results confirmed significantly increased expression of miR-141 in the retinas of OPTN (E50K) transgenic mice as compared to wild-type mice. In conclusion, these results show that certain miRNAs are differentially expressed in the retinas of OPTN (E50K) transgenic mice and may play roles in the pathogenesis of POAG induced by OPTN (E50K).

Purpose: Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men., Methods: We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed., Results: We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486)., Conclusion: Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.

Purpose: T lymphocyte immune responses are controlled by both co-stimulatory and co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator (BTLA) are all co-inhibitory molecules that negatively regulate the activation of T cells. In this study, we investigated the relationship between ten tagging SNPs in three co-inhibitory molecule genes and colorectal cancer (CRC)., Methods: We conducted a hospital-based case-control study consisting of 601 cases with CRC and 627 CRC-free individuals from the Heilongjiang Province of China., Results: The rs7421861 CT genotype was significantly associated with the risk of colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95% CI 1.012-1.706, P = 0.041). The rs2705535 TT genotype was associated with the risk of rectal cancer [OR 1.819 (1.093-3.027), P = 0.021]. There was statistical interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically and antagonistically interacted with soybeans, pork and alcohol intake and were associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with CRC risk (OR 1.221 P = 0.034)., Conclusions: These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.

Purpose: Given that mismatch repair (MMR) system plays an important role in recognizing and removing insertion/deletion mutations which occur during DNA replication, common variants associated with impaired MMR system may thus increase risk of colorectal cancer (CRC). Therefore, we aimed to demonstrate the associations between common variants in two MMR genes (hMLH1 and hMSH2) and CRC risk., Methods: We genotyped 10 intronic/promoter single-nucleotide polymorphisms (SNPs) of hMLH1 and hMSH2 in 451 CRC patients and 630 controls. Associations between genotypes and CRC risk were estimated using odds ratios and 95 % confidence intervals. Gene-gene interactions, as well as gene-environment interactions on CRC risk were also investigated., Results: We found that IVS15-214T>C and IVS11 + 107A>G of hMSH2 were significantly associated with CRC risk. In dominant model, variant carriers of the two SNPs could decrease risk of CRC by 31 % (ORadj = 0.69, 95 % CI 0.53-0.91, p < 0.01) and 33 % (ORadj = 0.67, 95 % CI 0.47-0.95, p = 0.02), respectively. In addition, IVS7-212T>A, IVS11+183A>G and IVS8+719T>C of hMSH2 were associated with the susceptibility to colon cancer rather than rectal cancer. ATTTGGGT and TCTTAGAC haplotypes were associated with 44 and 45 % decreased risk of CRC, respectively, while ATTTGAGT and TTTCAGAC haplotypes were associated with 1.37-fold and 2.49-fold increased risk of CRC, respectively. There was a significant three-way gene-gene interaction among hMSH2 IVS11+107A>G, IVS11+183A>G and IVS8+719T>C (p < 0.01). Significant gene-environment interactions were observed between hMSH2 IVS15-214T>C and IVS11+107A>G and cereals consumption (both with p < 0.01)., Conclusions: Our findings suggested that intronic SNPs, gene-gene and gene-environment interactions in hMSH2 might be associated with susceptibility to CRC.

Objective: To observe the characteristics of serum protein in patients with benign paroxysmal positional vertigo (BPPV) during the symptomatic period., Method: Fifty-five patients with BPPV and 58 control subjects were enrolled in the study. All the patients underwent the Dixe-Hallpike and Roll maneuver to confirm the type of BPPV. The average time of onset was (1.0 ± 0.8)days in the group of BPPV. The clinical features and the laboratory tests of serum protein electrophoresis, blood counts, and liver and kidney function were performed in both groups., Result: The levels of serum albumin (Alb), α1 globulin, α2 globulin and β globulin of BPPV group did not differ statistically in the two groups (P > 0.05); The γ-globulin levels were significantly higher in patients with BPPV than in controls (P < 0.05)., Conclusion: The γ-globulin levels are increased when BPPV is attacking.

To investigate whether Annexin 1 can protect a retinal ganglion cells line (RGC-5) from apoptosis as induced by serum deprivation. Annexin 1 location in RGC-5 cells was determined using an indirect immunofluorescent assay. Expression of Annexin 1 in RGC-5 cultures deprived of serum for 0, 2 days was semi-quantified by western blot and RT-PCR. Effects of varying concentrations of the Annexin 1 peptide fragment, Ac2-26, on the survival of the RGC-5 cells was determined, and apoptotic cells were quantified by flow cytometry. Immunoblot and RT-PCR analysis was preformed to identify caspase 3, bax and bcl-2 in RGC extracts. Annexin 1 was localized in the cytoplasm of RGC-5 cells and the expression of Annexin 1, caspase 3 and bax was upregulated in serum-deprived RGC-5 cells. Ac2-26 attenuated the apoptosis resulting from serum deprivation of RGC-5 in a concentration-dependent manner, decreased caspase 3 and bax levels and produced an increase of bcl-2 in cell lysates. Annexin 1, in specific the peptide fragment Ac2-26, may play an important role in decreasing apoptosis in serum-deprived RGC-5 cells.

Purpose: To identify a potential pathogenic mutation in a four-generation Chinese family with X-linked congenital nystagmus (XLCN)., Methods: Routine clinical examination and ophthalmic evaluation were performed on normal controls, two patients and two healthy members of the family. Genomic DNA was prepared from the peripheral blood of members of the family and from 50 normal controls. All coding exons and the intronic boundaries of the four-point-one (4.1), ezrin, radixin, moesin (FERM) domain-containing 7 (FRMD7) gene were amplified using polymerase chain reaction (PCR) followed by direct sequencing., Results: A previously unreported splicing mutation, c.163-1 G→T transversion (c.163-1 G>T), was detected preceding exon3 of FRMD7 in the patients but not in the unaffected family members and 50 unrelated healthy individuals., Conclusions: We identified a novel mutation (c.163-1 G→T) of FRMD7 in this Chinese family with XLCN. Our finding is the first report related to c.163-1 G→T mutation in FRMD7. The result expands the mutation spectrum of FRMD7 in association with congenital nystagmus.

Purpose: The paired box gene 6 (PAX6) on human chromosome 11p13 is an essential transcription factor for eye formation in animals. Mutations in PAX6 can lead to varieties of autosomal-dominant ocular malformations with aniridia as the major clinical signs. Known genetic alterations causing haplo-insufficiency of PAX6 include nonsense mutations, frame-shift mutations, splicing errors, or genomic deletions. The purpose of this study was to identify genetic defects as the underlying cause of familial aniridia in a large Chinese family., Methods: All exons of PAX6 in the proband were sequenced by the Sanger sequencing technique. The genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH). Quantitative real-time PCR was applied to verify the abnormal aCGH findings in the proband and to test five other family members., Results: There were no detectable pathogenic mutations in the exons of PAX6 in the proband. The aCGH analysis showed two copies of PAX6 but revealed a 566 kb hemizygous deletion of chromosome 11p13, including four annotated genes doublecortin domain containing 1 (DCDC1), DnaJ homolog subfamily C member 24 (DNAJC24), IMP1 inner mitochondrial membrane(IMMP1L), andelongation factor protein 4 (ELP4) downstream of PAX6. Quantitative real-time PCR verified the deletion in the proband and further identified the deletion in a blind fashion in four affected family members but not in the one with a normal phenotype., Conclusions: The 566 kb hemizygous deletion of chromosome 11p13 downstream of PAX6 should be the cause of the familial aniridia in this Chinese family, although two copies of PAX6 are intact. aCGH evaluation should be applied if there is a negative result for the mutation detection of PAX6 in patients with aniridia.

Purpose: To identify the mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome (MFS)., Methods: Patients and family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of six individuals in the family and 170 healthy Chinese individuals. All of the 65 coding exons and their flanking intronic boundaries of FBN1 were amplified in the proband by polymerase chain reaction and followed by direct sequencing. The mutation identified in the proband was screened in the other family members and the 170 healthy Chinese individuals by direct sequencing. Protein conservation analysis was performed in six species using an online ClustalW tool. Protein structure was modeled based on the Protein data bank and mutated in DeepView v4.0.1 to predict the functional consequences of the mutation., Results: A novel heterozygous c.3703T>C change in exon 29 of FBN1 was detected in the proband, which resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was also present in two family members but absent in the other, unaffected family members and the 170 healthy Chinese individuals. The mutant residue located in the calcium binding epidermal growth factor-like#15 domain is highly conserved among mammalian species and could probably induce conformation change of the domain., Conclusions: We indentified a novel p.S1235P mutation in FBN1, which is the causative mutation for MFS in this family. Our result expands the mutation spectrum of FBN1 and contributes to the study of the molecular pathogenesis of Marfan syndrome.

Purpose: To identify the genetic mutation associated with distinct cases of open-angle glaucoma noted in a Chinese family., Methods: Clinical examination and pedigree analysis were undertaken in a family with a large number of primary open-angle glaucoma cases. Venous blood samples were drawn from six affected and six unaffected subjects in the family. Genomic DNA was extracted. Linkage to the optineurin gene (OPTN) locus was not excluded. Potential mutation in OPTN was screened by polymerase chain reaction (PCR) analysis of its exon regions and direct sequencing., Results: A missense mutation, A1274G, in exon 10 of OPTN was identified in affected patients of the family. The corresponding amino acid change was Lys322Glu. This mutation was not found in unaffected family members of the family or in 87 unrelated normal controls., Conclusions: A novel mutation of a Lys322Glu change in OPTN is responsible for this familial case of primary open-angle glaucoma observed in northeastern China.

Purpose: The PAX6 gene encodes a transcriptional regulator involved in oculogenesis and other developmental processes such as aniridia, a congenital condition characterized by the underdevelopment of the eye's iris. Aniridia may be broadly divided into hereditary and sporadic forms. The function of the PAX6 gene in these two forms of aniridia is still poorly defined. Therefore, we carried out a mutation analysis of the PAX6 gene in northeastern Chinese families with aniridia to identify the role of the PAX6 gene in hereditary aniridia., Methods: Five aniridia patients from two northeastern Chinese families (Family 1 and Family 2) underwent full ophthalmologic examinations. Genomic DNA was prepared from venous leukocytes from these five patients, 10 non-carriers in these two families, as well as 100 healthy normal controls. The coding regions of PAX6 were analyzed by PCR amplification, direct sequencing and allele-specific cloning sequencing. RESULTS We identified two novel PAX6 mutations. The first is a 9 base pair (bp) deletion in exon 5 (c.483del9) that makes a PAX6 protein with de novo in-frame deletions of aspartic acid, isoleucine, and serine at the amino acid codon positions 41-43. The second is a heterozygous mutation (IVS10+1G>A) located at the boundary of exon 10 and intron 10., Conclusions: We identified two novel PAX6 mutations in familial aniridia from northeastern China, an ethnic group that is not well-studied. The genetic analysis confirms that these two novel mutations in PAX6 are capable of causing the classic aniridia phenotype. Therefore, by studying human familial aniridia cases, we demonstrated that PAX6 plays a role in hereditary aniridia.