Clinical features and prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease in Chinese patients.

OBJECTIVE: The objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD) in Chinese patients. METHODS: Clinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti-MDA5-positive or negative dermatomyositis, and with or without RP-ILD groups. Clinical features and prognostic factors were statistically compared among different groups. RESULTS: The serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ-glutamyl transpeptidase (γ-GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0], Z = 5.528; p < .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0], Z = -2.739, p = .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88, t = -2.542, p = .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77, t = -4.717, p < .001) were lower than those in anti-MDA5-negative counterparts. Among patients with anti-MDA5 antibody (Ab) with RP-ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5], Z = 2.664, p = .008), γ-GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0], Z = 3.136, p = .002) and positive rate of anti-RO-52 Ab (90.9% vs. 50.0%, χ2 = 7.222, p = .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74, t = -3.025, p = .029) was lower than those in their counterparts without RP-ILD. The SF level of anti-MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0], Z = 2.096, p = .030), anti-RO-52 Ab-positive rate ([16/18, 88.9%] vs. [9/16, 56.2%], χ2 = 4.636, p = .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP-ILD and death of patients with anti-MDA5-positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000; p < .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795. CONCLUSIONS: Anti-MDA5-positive dermatomyositis patients are prone to developing RP-ILD. Declined lymphocyte count is a critical risk factor for RP-ILD, probably acting as a simple and effective predictor for Chinese patients with anti-MDA5-positive dermatomyositis.

A catalase inhibitor: Targeting the NADPH-binding site for castration-resistant prostate cancer therapy.

Catalase (CAT) is an important antioxidant enzyme that breaks down H2O2 into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2 Å (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145 cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.

Construction of a genome instability-derived lncRNA-based risk scoring system for the prognosis of hepatocellular carcinoma.

Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, genome instability-associated lncRNAs (GILncRNAs) and their performance in clinical prognostic significance in hepatocellular carcinoma (HCC) are rarely reported. Our study constructed a computational framework integrating somatic mutation information and lncRNA expression profiles of HCC genome and we identified 88 GILncRNAs of HCC. Function enrichment analysis revealed that GILncRNAs were involved in various metabolism processes and genome instability of cancer. A genome instability-derived lncRNA-based gene signature (GILncSig) was constructed using training set data. The performance of GILncSig for outcome prediction was validated in testing set and The Cancer Genome Atlas (TCGA) set. The multivariate cox regression analysis and stratification analysis demonstrated GILncSig could serve as an independent prognostic factor for the overall survival of HCC patients. The time-dependent Receiver Operating Characteristic (ROC) curve illustrated GILncSig outperformed two recently published lncRNA signatures for overall survival prediction. The combination of GILncSig and tumor protein p53 (TP53) mutation status exhibited better prognostic performance in survival evaluation compared to TP53 mutation status alone. AC145343.1 was further validated to be a risk factor for HCC in vitro among GILncSig. Overall, our study provided a novel approach for identification of genome instability-associated lncRNAs and established an independent risk score system for outcome prediction of HCC patients, which provided a new insight for exploring in-depth mechanism and potential therapy strategy.

Interactive effect of sarcopenia and falls on vertebral osteoporotic fracture in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) had higher incidences of sarcopenia, falls, osteoporosis, and vertebral osteoporotic fractures (VOPF). Sarcopenia was associated with longer disease duration, higher disease activity, and more severe RA. The interactive effect of sarcopenia and falls was associated with a higher risk of VOPF in patients with RA. PURPOSE: Whether sarcopenia and falls are a risk factor for vertebral fracture in RA patients has not been demonstrated. This study aimed to explore the incidence of vertebral osteoporotic fracture (VOPF) and its relationship with sarcopenia and falls in RA patients. METHODS: A total of 474 RA patients and 156 controls were enrolled in this study. Anteroposterior and lateral X-ray examinations of the vertebral column (T4-L4) were used for the semiquantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. Skeletal muscle mass was measured by direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA method). RESULTS: RA patients had an increased risk of sarcopenia (62.4% vs 9.0%, x2 = 47.478, P < 0.001), falls (30.2% vs 3.2%), osteoporosis (OP) (33.5% vs 12.8%, x2 = 134.276, P < 0.001), and VOPF (20.3% vs 3.8%, x2 = 47.478, P < 0.001) than controls. Patients with sarcopenia were more likely to have VOPF than RA without sarcopenia (24.0% vs 14.0%, x2 = 6.802, P = 0.009). RA with sarcopenia and prior falls had the highest incidences of VOPF (36.7%). Older age (OR = 1.056, P < 0.001, 95% CI 1.030-1.083), falls (OR = 2.043, P = 0.003, 95% CI 1.238-3.371), OP (OR = 1.819, P = 0.034, 95% CI 1.046-3.163), and usage of glucocorticoids (GCs) (OR = 1.862, P = 0.022, 95% CI 1.093-3.172) were risk factors for VOPF in RA patients, while a higher skeletal muscle index (SMI) was a protective factor (OR = 0.754, P = 0.038, 95% CI 0.578-0.984) for VOPF in RA patients. CONCLUSIONS: The interactive effect of sarcopenia and falls is associated with a higher risk of VOPF in patients with RA.

Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study.

BACKGROUND: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

A Linear Relationship Between a Body Shape Index and Risk of Incident Type 2 Diabetes: A Secondary Analysis Based on a Retrospective Cohort Study in Japan.

PURPOSE: This study aimed to evaluate the association between a body shape index (ABSI) and incident type 2 diabetes and to explore the shape of their relationship in a cohort of Japanese adults. PATIENTS AND METHODS: Data from 15,462 Japanese adults aged 18-79 years attending the NAGALA study (NAfld in the Gifu Area, Longitudinal Analysis) were used. Body weight, height, and waist circumference were measured. Blood samples were measured for serum lipid, glucose, and HbA1c. The risk of incident type 2 diabetes according to ABSI was estimated using multivariate Cox regression models. We examined a potential nonlinear relationship using a smoothing function analysis. Subgroup analyses were conducted according to age, gender, smoking status, alcohol intake, fatty liver, and BMI. RESULTS: After adjusting for potential confounding factors (age, gender, smoking status, alcohol intake, fatty liver, systolic blood pressure, BMI, fasting plasma glucose, HbA1c, HDL-cholesterol, triglycerides), a linear relationship was observed between ABSI and risk of type 2 diabetes. The hazard ratio (HR) and 95% confidence intervals (95% CI) for incident type 2 diabetes with ABSI (10-2 m11/6kg-2/3) were 1.51 (1.13, 2.01) (p=0.005). When ABSI was handled as categorical variable, the HRs and 95% CIs in the quartile 2 to 4 versus the quartile 1 were 0.97 (0.67, 1.41), 1.21 (0.85, 1.72) and 1.30 (0.92, 1.83), respectively (P for trend = 0.046). Subgroup analyses showed that the association stably existed in different subgroups including gender, age, smoking status, alcohol intake, fatty liver, and BMI. CONCLUSION: ABSI was linearly associated with an elevated risk of incident type 2 diabetes across the full range of ABSI, independent of gender, age, smoking status, alcohol intake, fatty liver, SBP, BMI, FPG, HbA1c, HDL-cholesterol, and triglycerides.

Correction to: Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis.

The authors regrets that the original published version of this article contained errors.

Prevalence and risk factors associated with vertebral osteoporotic fractures in patients with rheumatoid arthritis.

OBJECTIVES: To explore the prevalence and risk factors of osteoporosis (OP) and vertebral osteoporotic fracture (VOPF) in patients with rheumatoid arthritis (RA). METHODS: Anteroposterior and lateral X-ray examination of the vertebral column (T4-L4) was used for the semi-quantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: Of 865 RA patients, the prevalence of OP and VOPF was 33.6% and 20.2%, respectively. Patients with OP or VOPF were older, and had longer term use and a larger daily amount and cumulative dose of glucocorticoids (GCs), longer disease duration, and higher Health Assessment Questionnaire (HAQ) scores and Sharp scores than patients without OP or VOPF (P < 0.05). OP was also correlated with higher disease activity. The patients treated with GCs had higher incidences of OP and VOPF than the patients without GCs (P < 0.05). The cutoff values in the area under curve (AUC) of the daily dose or treatment course of GCs-VOPF were 9 mg and 37.5 days. Older age, female sex, and a higher Sharp score were risk factors for OP in RA patients, while higher BMI was a protective factor. Older age and a high GC daily dose were risk factors for VOPF in RA patients. CONCLUSIONS: RA patients have a high prevalence of OP and VOPF. Older age, female sex, lower BMI, and higher activity and severity of RA are closely related with OP. Older age and a higher GC daily dose are risk factors for VOPF in RA patients. Key Points • Older age, female sex, lower BMI, and a higher Sharp score were risk factors for OP in RA patients. • Older age and a high GC daily dose were risk factors for VOPF in RA patients. • OP and VOPF in RA patients were correlated with longer disease duration and higher severity of RA.

Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF. METHODS: This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSH-ACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSH-ACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test. RESULTS: A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models. CONCLUSIONS: COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict short-term prognosis in Chinese patients with HBV-ACLF.

Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-ß.

Mindin, which is a highly conserved extracellular matrix protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes, and immune responses. The aim of the present study was to assess whether mindin contributes to the development of atherosclerosis. A significant up-regulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/- mice after high-fat diet treatment. Mindin-/-ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis. The Mindin-/-ApoE-/- mice exhibited significantly ameliorated atherosclerotic burdens in the entire aorta and aortic root and increased atherosclerotic plaque stability. Moreover, bone marrow transplantation further demonstrated that mindin deficiency in macrophages was largely responsible for the alleviated atherogenesis. The Lyz2-mindin-TG mice exhibited the opposite phenotype. Mindin deficiency enhanced foam cell formation by increasing the expression of cholesterol effectors, including ABCA1 and ABCG1. The mechanistic study indicated that mindin ablation promoted LXR-ß expression via a direct interaction. Importantly, LXR-ß inhibition largely reversed the ameliorating effect of mindin deficiency on foam cell formation and ABCA1 and ABCG1 expression. The present study demonstrated that mindin deficiency serves as a novel mediator that protects against foam cell formation and atherosclerosis by directly interacting with LXR-ß.

Mitochondria: The hub of energy deprivation-induced autophagy.

Macroautophagy/autophagy, a process that is highly conserved from yeast to mammals, delivers unwanted cellular contents to lysosomes or the vacuole for degradation. It has been reported that autophagy is crucial for maintaining glucose homeostasis. However, the mechanism by which energy deprivation induces autophagy is not well established. Recently, we found that Mec1/ATR, originally identified as a sensor of DNA damage, is essential for glucose starvation-induced autophagy. Mec1 is recruited to mitochondria where it is phosphorylated by activated Snf1 in response to glucose starvation. Phosphorylation of Mec1 leads to the assembly of a Snf1-Mec1-Atg1 module on mitochondria, which promotes the association of Atg1 with Atg13. Furthermore, we found that mitochondrial respiration is specifically required for glucose starvation-induced autophagy but not autophagy induced by canonical stimuli. The Snf1-Mec1-Atg1 module is essential for maintaining mitochondrial respiration and regulating glucose starvation-induced autophagy.

Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25µg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude.

Vaccine Serotypes of Streptococcus pneumoniae with High-level Antibiotic Resistance Isolated More Frequently Seven Years After the Licensure of PCV7 in Beijing.

BACKGROUND: Streptococcus pneumoniae 7-valent conjugate vaccine (PCV7) was made available in China in the private sector in September 2008. METHODS: This study investigated the serotype distribution, antibiotic resistance, and molecular characteristics of S. pneumoniae in hospitalized pediatric patients. Pneumococcal isolates were collected from hospitalized children younger than 14 years. Their serotypes were determined using Quellung reactions with antisera; antibiotic resistance against 13 antimicrobials was tested using the E-test method or disc diffusion. The sequence types (STs) were analyzed with multilocus sequence typing. RESULTS: A total of 187 pneumococcal specimens were collected, including 21 invasive and 166 noninvasive isolates. The prevailing serotypes were 19F (31.6%), 19A (19.8%), 23F (11.2%), 6A (9.1%), 14 (9.1%) and 15B (5.9%). The coverage rates of PCV7, PCV10 and PCV13 were 56.2% (105/187), 56.7% (106/187) and 86.1% (161/187), respectively. The overall nonsusceptibility rate against penicillin was 8.0%; however, this rate would have been 91.5% if based on an oral breakpoint. All but one of the isolates were highly resistant to erythromycin. Multidrug resistance was exhibited by 177 (94.7%) isolates. The 5 predominant multilocus sequence typings for all pneumococci were ST271 (24.1%), ST320 (18.2%), ST81 (7.5%), ST876 (7%) and ST3397 (5.3%), which were primarily related to serotypes 19F, 19A, 23F, 14 and 15B, respectively. CC271 was the most frequent antibiotic-resistant complex clone. CONCLUSIONS: The coverage rates of PCVs were high, and the antibiotic resistance rates were of serious concern among hospitalized children. Universal immunization using PCVs would likely prevent episodes of S. pneumoniae diseases and the spread of antibiotic resistance in Beijing.

Chronic adjunction of 1-deoxynojirimycin protects from age-related behavioral and biochemical changes in the SAMP8 mice.

Several studies have indicated that a caloric restriction mimetic or treatment for type 2 diabetes may reverse brain aging. Therefore, we investigated the effect of 1-deoxynojirimycin (DNJ), an alkaloid acting as an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. SAMP8 mice were randomly assigned to a control group labeled "old" or to the 10- or 20-mg/kg/day DNJ groups. The mice in the DNJ groups were administered DNJ orally from 3 to 9 months of age, and then, a "young" control group was added to analyze the age effect. The old controls exhibited significant declines in sensorimotor ability, open-field anxiety, spatial and nonspatial memory abilities, and age-related biochemical changes, including decreased serum insulin level; increased levels of insulin-like growth factor 1 receptor, presynaptic protein synaptotagmin-1, and astrocyte activation; and decreased levels of insulin receptor, brain-derived neurotrophic factor, presynaptic protein syntaxin-1, and acetylation of histones H4 at lysine 8 in the dorsal hippocampus. Significant correlations exist between the age-related behavioral deficits and the serological and histochemical data. Chronic DNJ treatment alleviated these age-related changes, and the 20-mg/kg/day DNJ group showed more significant improvement. Thus, DNJ may have the potential to maintain successful brain aging.

Serotypes, antibiotic susceptibilities, and multi-locus sequence type profiles of Streptococcus agalactiae isolates circulating in Beijing, China.

BACKGROUND: To investigate the serotypes, antibiotic susceptibilities, and multi-locus sequence type (MLST) profiles of Streptococcus agalactiae (S. agalactiae) in Beijing to provide references for the prevention and treatment of S. agalactiae infections. METHODS: All isolates were identified using the CAMP test and the latex-agglutination assay and serotyped using a Strep-B-Latex kit, after which they were assessed for antibiotic susceptibility, macrolide-resistance genes, and MLST profiles. RESULTS: In total, 56 S. agalactiae isolates were identified in 863 pregnant women (6.5%). Serotypes Ia, Ib, II, III, and V were identified, among which types III (32.1%), Ia (17.9%), Ib (16.1%), and V (14.3%) were the predominant serotypes. All isolates were susceptible to penicillin and ceftriaxone. The nonsusceptiblity rates measured for erythromycin, clarithromycin, azithromycin, telithromycin, clindamycin, tetracycline, and levofloxacin were 85.7%, 92.9%, 98.2%, 30.4%, 73.2%, 91%, and 39.3%, respectively. We identified 14 sequence types (STs) for the 56 isolates, among which ST19 (30.4%) was predominant. The rate of fluoroquinolone resistance was higher in serotype III than in the other serotypes. Among the 44 erythromycin-resistant isolates, 32 (72.7%) carried ermB. CONCLUSION: S. agalactiae isolates of the serotypes Ia, Ib, III, and V are common in Beijing. Among the S. agalactiae isolates, the macrolide and clindamycin resistance rates are extremely high. Most of the erythromycin-resistant isolates carry ermB.

Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8.

Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of an insulin system and H4K8ac might be associated with the alleviation.

Chronic acarbose treatment alleviates age-related behavioral and biochemical changes in SAMP8 mice.

The administration of maintaining the homeostasis of insulin/insulin-like growth factor 1 (IGF-1) signaling and/or glucose metabolism may reverse brain aging. In the present study, we investigated the effect of acarbose, an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. The SAMP8 mice were randomly divided into old control group and acarbose-treatment group. The mice in the acarbose group were administered acarbose (20 mg/kg/d, dissolved in drinking water) orally from 3 to 9 months of age when a new group of 3-month-old mice was added as young controls. The results showed that the aged controls exhibited declines in sensorimotor ability, open field anxiety, spatial and non-spatial memory abilities, decreased serum insulin levels, increased IGF-1 receptor and synaptotagmin 1 (Syt1) levels and decreased insulin receptor, brain-derived neurotrophic factor (BDNF) and syntaxin 1 (Stx1) levels in the hippocampal layers. The age-related behavioral deficits correlated with the serological and histochemical data. Chronic acarbose treatment relieved these age-related changes, especially with respect to learning and memory abilities. This protective effect of acarbose on age-related behavioral impairments might be related to changes in the insulin system and the levels of BDNF, IGF-1R, and the pre-synaptic proteins Syt1 and Stx1. In conclusion, long-term treatment with acarbose ameliorated the behavioral deficits and biochemical changes in old SAMP8 mice and promoted successful aging. This study provides insight into the potential of acarbose for the treatment of brain aging.

[Optical Path Difference Analysis and Simulation of Four Typical Rotary Type Interferometer].

The four kinds of the structure characteristics of rotary type interferometer are mainly analyzed from the classical Michelson interferometer structure in the paper. The Optical path difference between the interferometer and the rotation angle is also analyzed. By setting parameters, the four kinds of rotary type optical path difference of the interferometer are simulated based on the optical path difference formula. The rotation velcocity of the four kinds of interferometers is also simulated. By simulation and contrast of the optical path difference, the relationship is intuitively reflect by figure between the optical path difference and the rotation angle. The scope of the rotation angle is discussed within 3% of the velocity errors. It is the very good reference significance to study the structure and properties of the interferometer by analyzing and simulating the optical path difference discussed in the paper.

[Research advance in prevention policies of neonatal group B Streptococcus infection].

Group B Streptococcus (GBS) is responsible for two distinct clinical syndromes in the newborn period categorised as either early- or late-onset GBS disease. Maternal GBS colonization of gastrointestinal tract or vaginal is the major risk factor for GBS diseases. There are two main strategies for identifying women at risk of giving birth to a GBS-infected infant: universal screening strategy and risk-based assessment. In the United States and other countries, the implementation of maternal intrapartum antibiotic prophylaxis policies has significantly reduced the incidence of early-onset neonatal GBS disease, but has little effect on the incidence of late-onset GBS disease. Penicillin is the first choice for antibiotic prophylaxis treatment. GBS strains which are isolated from pregnant women who are allergic to penicillin should undergo antibiotic susceptibility testing. Antibiotic prophylaxis measures have some disadvantages, so researchers should actively develop other precautions to prevent GBS infection.