[Effects of celastrol on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease].

Objective: To investigate the effect of celastrol (CEL) on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease (NAFLD). Methods: Eighteen male C57BL/6J mice were randomly divided into normal control (NC, n=6), high-fat diet (HFD, n=6) and celastrol group (HFD+CEL, n=6). The normal control group was fed with regular diet, and the high-fat diet and celastrol group were fed with high-fat diet for 12 weeks. After successful modeling, celastrol group were injected with 100 µg⋅kg-1⋅d-1 celastrol intraperitoneally for 4 weeks, and NC and HFD group were injected intraperitoneally with the same doses of normal saline. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in mouse after 4-weeks of intervention. HE and Oil Red O staining were used to observe the pathomorphological changes and lipid droplet deposition in mouse liver, and the findings were scored according to NAFLD activity score (NAS). Western blot was used to detect the expression levels of liver microtubule associated protein 1 light chain 3 (LC3), P62, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activated transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), cleaved Caspase-3(cleaved caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax).TUNEL staining was used to observe the apoptosis of hepatocytes. One-way analysis of variance was used for the intergroup comparison. Results: Serum levels of ALT (68.71±8.57) U/L, AST (209.63±28.64) U/L, TG (0.97±0.14) mmol/L, TC (4.12±0.64) mmol/L, and LDL -C (0.40±0.06) mmol/L were lower in celastrol group mouse than HFD group [(110.19±10.79) U/L, (399.72±73.47) U/L, (1.44±0.13) mmol/L, (5.65±0.54) mmol /L, (0.61±0.07) mmol/L] (P<0.05); while the serum HDL-C level (1.29±0.17) mmol/L was higher in celastrol than HFD group (0.72±0.13) mmol/L (P<0.05). HE and Oil Red O staining showed that lipid deposition and intralobular inflammation were apparent in the liver tissue of HFD group mouse, and the NAS score was significantly increased, while the hepatocyte steatosis and intralobular inflammation were alleviated after celastrol intervention, and the NAS score was decreased significantly (P<0.05). Compared with HFD group, the ratio of LC3II/I was significantly increased in the liver of celastrol group mouse, and the P62 was significantly decreased (P<0.05). Meanwhile, the expression level of GRP78, p-PERK/PERK , ATF4, and CHOP was significantly lower in celastrol than HFD group (P<0.05). In addition, the expressions of cleaved caspase-3 and Bax were significantly lower in celastrol than HFD group, and the expression of Bcl-2 was significantly increased (P<0.05). At the same time, the apoptosis rate of hepatocytes was also significantly lower in celastrol than HFD group (P<0.05). Conclusion: Celastrol can effectively alleviate the lipid deposition, protect hepatocytes and delay the progression of non-alcoholic fatty liver disease in mouse liver with non-alcoholic fatty liver disease. In addition, its mechanism of action may be related to the induction of autophagy, inhibition of endoplasmic reticulum stress PERK/ATF4/CHOP pathway and its mediated apoptosis.

What happens to cancer survivors attending a structured cancer survivorship clinic? Symptoms, quality of life and lifestyle changes over the first year at the Sydney Cancer Survivorship Centre clinic.

BACKGROUND: Sydney Cancer Survivorship Centre (SCSC) clinic provides multidisciplinary care after primary adjuvant treatment, with ~ 40% of attendees continuing follow-up with SCSC. METHODS: SCSC survivors completed measures of symptoms, quality-of-life and lifestyle factors at initial visit (T1), first follow-up (T2) and 1 year (T3). Analyses used mixed effect models, adjusted for age, sex and tumour type. RESULTS: Data from 206 survivors (2013-2019) were included: 51% male; median age 63 years; tumour types colorectal 68%, breast 12%, upper gastrointestinal 12%, other 8%. Mean time from: T1 to T2, 3.6 months; T1 to T3, 11.8 months. Mean weight remained stable, but 45% (35/77) of overweight/obese survivors lost weight from T1 to T3. Moderately-intense aerobic exercise increased by 63 mins/week at T2, and 68 mins/week T3. Proportion meeting aerobic exercise guidelines increased from 20 to 41%. Resistance exercise increased by 26 mins/week at T2. Global quality-of-life was unchanged from T1 to T2, improving slightly by T3 (3.7-point increase), mainly in males. Mean distress scores were stable, but at T3 the proportion scoring 4+/10 had declined from 41 to 33%. At T3, improvements were seen in pain, fatigue and energy, but > 20% reported moderate-severe fatigue, pain or sleep disturbance. Proportion reporting 5+ moderate-severe symptoms declined from 35% at T1 to 26% at T3, remaining higher in women. CONCLUSIONS: Survivors attending SCSC increased exercise by 3 months, and sustained it at 1 year. Most overweight/obese survivors avoided further weight gain. Survivors had relatively good quality-of-life, with improvement in many symptoms and lifestyle factors at 1 year.

[Research progress on the effect of selective autophagy receptor p62 on fibrotic diseases].

Selective autophagy keeps cell homeostasis by degrading aggregated proteins, damaged or over-abundant organelles, and other cytoplasmic substances. The maintenance of its normal function needs to ensure that the autophagy receptor can effectively recognize and isolate undegraded substances. As an important autophagy receptor protein, p62 participates in the process of selective autophagy by mediating multiple signaling pathways. Fibrosis is a pathological feature of most chronic inflammatory diseases. When fibrosis develops for a long time, it will cause substantial scar formation and eventually lead to cell dysfunction and organ failure. The accumulation, overexpression and ectopic expression of p62 can aggravate the occurrence and development of lung, liver and kidney fibrosis diseases. Therefore, it is very critical to explore the effect of selective autophagy receptor p62 on fibrotic diseases.

[The study of the impact by atractylenolide-1 on inflammatory cytokine, autophagy and apoptosis in alveolar macrophages of silicosis patients].

Objective: To explore the effect of atractylenolide-1 (ATL-Ⅰ) on alveolar macrophages in silicosis patients. Methods: In December 2019, 12 male silicosis patients treated in Beidaihe Sanatorium for Chinese Coal Miners from July to September 2019 were selected by random sampling. Their alveolar macrophages were collected and divided into control group, ATL-Ⅰ group (100 µmol/L) and dimethyl sulfoxide (DMSO) group (100 µmol/L) . The exprossion levels of inflammatory factor interleukin-1ß (IL-1ß) , interleukin-6 (IL-6) , tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay. The expression levels of autophagy associated protein microtubule associated protein light chain 3 (LC3) , autophagy substrate protein p62, lysosome associated membrane protein 2 (LAMP2) , apoptosis associated protein Cleaved caspase-3, nuclear factor kappa B (NF-κB) and its phosphorylated form (p-NF-κB) were detected by Western blot. Results: Compared with the control group and DMSO group, the expression levels of IL-1ß, IL-6, TNF-α in alveolar macrophages decreased significantly in the ATL-Ⅰ group (P<0.05) , and the expression levels of p-NF-κB, the ratio of LC3-Ⅱ/LC3-Ⅰ also decreased significantly in the ATL-Ⅰ group (P<0.05) . However, the expression levels of NF-κB, LAMP2, p62 and Cleaved caspase-3 in the ATL-Ⅰ group were not statistically different from those in the control group and DMSO group (P>0.05) . There was no statistically significant differences in the expression of the above indexes between the control group and DMSO group (P>0.05) . Conclusion: ATL-Ⅰ may reduce the release of inflammatory factors from alveolar macrophages and inhibit the activity of autophagy in silicosis patients, but it may not reduce the level of apoptosis.

Decreased expression of SorCS1 in colorectal cancer: An independent predictor of poor prognosis.

Previously, we identified that sortilin related VPS10 domain containing receptor 1 (SorCS1) was hypermethylated in colorectal cancer (CRC) tissues. Here, we aimed to investigate the association between CRC and SorCS1. DNA methylation was determined by methylation-specific polymerase chain reaction (MSP) or quantitative real-time methylation analysis (MethyLight). Colorectal cancer tissue specimens from 239 patients that had undergone surgical treatment were evaluated using immunohistochemistry (IHC) analysis for the expression of SorCS1 and correlated with clinicopathological variables and prognosis. We found that SorCS1 was hypermethylated in CRC cell lines and 67.5% (27/40) CRC tumor tissues. The loss of SorCS1 mRNA (p<0.001) and protein expression (p=0.033) were highly correlated with promoter methylation. In addition, SorCS1 expression was significantly increased in younger patients (p=0.006), low CEA level (p<0.001) and pT1-2 stage (p=0.005). Survival analysis revealed that decreased expression of SorCS1 was an independent factor for predicting the increased risk of recurrence (p=0.024) and poor overall survival (p=0.006). Subgroup analysis for CEA level, pT and pN classifications showed that SorCS1 retained its stratified significance only in patients with low CEA level, pT3-4 tumors and pN1-2 lymph node status. Our findings suggest that SorCS1 is epigenetically inactivated in a substantial fraction of CRC, and its expression may be a promising prognostic factor in CRC patients.

[Treatment of postprandial discomfort syndrome in the elderly: a multi-centered prospective randomized controlled clinical study].

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

[The clinical characteristics of 89 cases of non-tuberculous mycobacterium pulmonary disease complicated with tracheobronchial lesions].

Objective: To explore the clinical characteristics of non-tuberculous mycobacterium(NTM) pulmonary disease complicated with tracheobronchial lesions. Methods: From January 2014 to December 2018, there were 1 006 patients who were admitted to Guangzhou Chest Hospital for the first time and received examination by bronchoscopy. A total of 89 patients with complete data were selected, including 40 males and 49 females, aged 20 to 85 years, with 46 patients (52%) aged 60 years or older. The clinical symptoms and signs of the patients were analyzed with chest imaging, bronchoscopy and pathological examination results. Comparisons between groups were made by Chi-square test and t test. Results: The number of patients with NTM complicated with tracheobronchial lesions accounted for 8.9%(89/1 006) of those hospitalized with NTM and received bronchoscopy during the same period. Clinical symptoms included cough and sputum (89/89), different degrees of hemoptysis or blood sputum (52/89), and shortness of breath (50/89). Chest CT showed that 72 cases (72/89, 81%) had lung lesions involving more than 3 lung fields, and 83 cases (93%) had bronchiectasis and 63 cases (63/89, 71%) with cavities. Pulmonary atelectasis was shown in 45 cases (45/89, 51%). By bronchoscopy, 39 cases (39/89, 44%) were diagnosed as tuberculous lesions involving bilateral upper bronchi, while lesions of the right lower bronchus was found in 27 cases (27/89, 30%).The percentage of patients with multilobar bronchial involvement was 50.6%(45/89). The morphological characteristics of the bronchial lesions included scar stenosis or atresia in 63 cases (63/89, 71%), hyperemia and edema in 46 cases (46/89, 52%), and multiple types of lesions in 48 cases (48/89, 54%). Conclusions: Patients with NTM lung disease complicated with tracheobronchial inflammatory lesions did not have specific manifestations clinically. Lung lesions are extensive, often accompanied by bronchiectasis and cavity formation. Endoscopic changes were mostly manifested as multilobar tracheobronchial involvement characterized by scar stenosis, congestion and edema, mainly involving bilateral upper bronchi and the right lower bronchus.

[Effect of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease].

Objective: To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease. Methods: An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups. Results: Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (P < 0.05). DCFH-DA test results showed that the fluorescence intensity of reactive oxygen species in the oleic acid group was 41.21% ± 4.23%, while the fluorescence intensity of reactive oxygen species in the low and high-dose metformin groups were reduced to 27.44% ± 3.91%, and 17.55% ± 5.11%, respectively and the differences between the groups were statistically significant (P < 0.05). The results of flow cytometry analysis showed that the cell apoptosis rate of the OA group was significantly higher than that of the Con group (12.12% ± 0.72% vs. 3.04% ± 0.57%, P < 0.05).The apoptosis rate of HepG2 cells was significantly reduced after metformin treatment at low and high doses (8.71% ± 0.71%, 5.71% ± 0.61%, P < 0.05). Western blot results showed that compared with the Con group, the expressions of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 were increased in the OA group, while the B-cell lymphoma 2 were decreased (P < 0.05). The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05). Conclusion: Metformin can effectively alleviate steatosis and improve the HepG2 function in cell model of nonalcoholic fatty liver disease. The mechanism of metformin may be related to the reduction of oxidative stress injury, the regulation of protein expression related to mitochondrial apoptosis pathway and the inhibition of cell apoptosis.

[The study of smoking impact on autophagy in alveolar macrophages of human silicosis].

Objective: To investigate the effect of smoking on autophagy in alveolar macrophages (AMs) of silicosis patients. Methods: In December 2019, a random sampling method was used to select 42 male patients with silicosis (19 cases of stage II and 23 cases of stage III) who were treated with large volume whole lung lavage from August to December 2017 in the Beidaihe sanatorium. According to the different smoking index of the study subjects (smoking index=smoking cigarette consumptions per day×years of smoking) , we divided them into high (Smoking index>400) , medium (200≤smoking index≤400) , low (smoking index <200) and non-smoking group. The levels of autophagy related proteins LC3, Beclin1, p62 and apoptosis related protein Cleaved Caspase-3 were detected by Western blot. The effects of smoking on autophagy activity of AMs in silicosis were analyzed. Results: The ratio of autophagy related protein LC3 II/LC3 I, the expression of Beclin1, p62, and apoptosis related protein Cleaved Caspase-3 in the high smoking group were significantly higher than that of the middle, low smoking group and the non-smoking group (P<0.05) . Conclusion: Smoking can aggravate the dysfunction of autophagic degradation in silicosis patients' AMs, which may accelerate the progress of silicosis through increasing apoptosis in AMs.

Orbital-Selective Kondo Entanglement and Antiferromagnetic Order in USb_{2}.

In heavy-fermion compounds, the dual character of f electrons underlies their rich and often exotic properties like fragile heavy quasiparticles, a variety of magnetic orders and unconventional superconductivity. 5f-electron actinide materials provide a rich setting to elucidate the larger and outstanding issue of the competition between magnetic order and Kondo entanglement and, more generally, the interplay among different channels of interactions in correlated electron systems. Here, by using angle-resolved photoemission spectroscopy, we present the detailed electronic structure of USb_{2} and observe two different kinds of nearly flat bands in the antiferromagnetic state of USb_{2}. Polarization-dependent measurements show that these electronic states are derived from 5f orbitals with different characters; in addition, further temperature-dependent measurements reveal that one of them is driven by the Kondo correlations between the 5f electrons and conduction electrons, while the other reflects the dominant role of the magnetic order. Our results on the low-energy electronic excitations of USb_{2} implicate orbital selectivity as an important new ingredient for the competition between Kondo correlations and magnetic order and, by extension, in the rich landscape of quantum phases for strongly correlated f electron systems.

Health concerns of cancer survivors after primary anti-cancer treatment.

PURPOSE: Cancer survivors experience significant health concerns compared to the general population. Sydney Survivorship Clinic (SSC) is a multi-disciplinary clinic aiming to help survivors treated with curative intent manage side effects, and establish a healthy lifestyle. Here, we determine the health concerns of survivors post-primary treatment. METHODS: Survivors completed questionnaires assessing symptoms, quality of life (QOL), distress, diet, and exercise before attending SSC, and a satisfaction survey after. Body mass index (BMI), clinical findings and recommendations were reviewed. Descriptive statistical methods were used. RESULTS: Overall, 410 new patients attended SSC between September 2013 and April 2018, with 385 survivors included in analysis: median age 57 years (range 18-86); 69% female; 43% breast, 31% colorectal and 19% haematological cancers. Median time from diagnosis, 12 months. Common symptoms of at least moderate severity: fatigue (45%), insomnia (37%), pain (34%), anxiety (31%) and with 56% having > 5 moderate-severe symptoms. Overall, 45% scored distress ≥ 4/10 and 62% were rated by clinical psychologist as having 'fear of cancer recurrence'. Compared to population mean of 50, mean global QOL T-score was 47.2, with physical and emotional well-being domains most affected. Average BMI was 28.2 kg/m2 (range 17.0-59.1); 61% overweight/obese. Only 31% met aerobic exercise guidelines. Overall, 98% 'agreed'/'completely agreed' attending the SSC was worthwhile, and 99% would recommend it to others. CONCLUSION: Distress, fear of cancer recurrence, fatigue, obesity and sedentary lifestyle are common in cancer survivors attending SSC and may best be addressed in a multi-disciplinary Survivorship Clinic to minimise longer-term effects. This model is well-rated by survivors.

[Effect of alcohol drinking on sputum conversion at the end of second month and outcome of smear-positive pulmonary tuberculosis patients].

Objective: To explore the effect of alcohol drinking on sputum culture conversion at the end of second month and outcome of smear-positive pulmonary tuberculosis (PTB) patients. Methods: Total 2 067 patients aged 18 years and above diagnosed and treated from 2008 to 2011 in 49 TB institutions from 8 provinces, antonomous regions and municipalities were enrolled, according to tuberculosis situation and regional distribution in China. Those patients were divided into three groups according to alcohol drinking, including never alcohol drinker group, ever-alcohol drinker group and current alcohol drinker group, respectively. Chi-square test was used to compare the following variables among the three groups: adverse action, lesions absorption, cavity size, sputum-culture results at the end of the 2(nd) month of treatment, and treatment outcome. Multivariate Logistic regression was used to explore that whether alcohol drinking was risk factor of poor treatment effect. Results: Among the 2 067 smear-positive PTB patients, never drinkers, ex-drinkers and current drinkers account for 55.2% (1 140/2 067), 36.5% (755/2 067), 8.3% (172/2 067), respectively. Among patients of never drinkers, ex-drinkers and current drinkers groups, sputum-culture conversion rate at the end of the 2(nd) month of treatment were 86.1%, 81.3% and 83.0%, respectively (χ(2)=6.782, P=0.033); the difference in treatment outcome was significant (χ(2)=13.620, P=0.034). Treatment success rate were 83.9%, 81.1% and 79.7%, respectively; failure rate was 6.4%, 10.3% and 9.9%, respectively, and fatality rate were 2.1%, 2.3% and 4.1%, respectively. Multivariate Logistic regression analysis showed that non-sputum conversion of the end of 2(nd) month and fatality rate of ex-drinkers were 1.431 and 1.668 times higher than never drinkers, respectively; non-sputum conversion of the end of 2(nd) month of current drinkers was 1.256 times higher than never drinkers. Conclusion: Alcohol drinking affects the treatment effectiveness of tuberculosis, which increased risk of culture-positive rate of the end of 2(nd) month and fatality rate.

Band Dependent Interlayer f-Electron Hybridization in CeRhIn_{5}.

A key issue in heavy fermion research is how subtle changes in the hybridization between the 4f (5f) and conduction electrons can result in fundamentally different ground states. CeRhIn_{5} stands out as a particularly notable example: when replacing Rh with either Co or Ir, antiferromagnetism gives way to superconductivity. In this photoemission study of CeRhIn_{5}, we demonstrate that the use of resonant angle-resolved photoemission spectroscopy with polarized light allows us to extract detailed information on the 4f crystal field states and details on the 4f and conduction electron hybridization, which together determine the ground state. We directly observe weakly dispersive Kondo resonances of f electrons and identify two of the three Ce 4f_{5/2}^{1} crystal-electric-field levels and band-dependent hybridization, which signals that the hybridization occurs primarily between the Ce 4f states in the CeIn_{3} layer and two more three-dimensional bands composed of the Rh 4d and In 5p orbitals in the RhIn_{2} layer. Our results allow us to connect the properties observed at elevated temperatures with the unusual low-temperature properties of this enigmatic heavy fermion compound.

Nuts and Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: We review recent epidemiological and clinical studies investigating the consumption of tree nuts and peanuts and cardiovascular disease (CVD) mortality as well as CVD risk factors. RECENT FINDINGS: A greater consumption of tree nuts and peanuts is associated with a reduced risk of CVD mortality, as well as lower CVD events. Furthermore, risk factors associated with the development of CVD such as dyslipidemia, impaired vascular function, and hypertension are improved with regular tree nut and peanut consumption through a range of mechanism associated with their nutrient-rich profiles. There is weak inconsistent evidence for an effect of nut consumption on inflammation. There is emerging evidence that consuming tree nuts reduces the incidence of non-alcoholic fatty liver disease (NAFLD) and promotes diversity of gut microbiota, which in turn may improve CVD outcomes. Evidence for CVD prevention is strong for some varieties of tree nuts, particularly walnuts, and length of supplementation and dose are important factors for consideration with recommendations.

Association of clinicopathological features of melanoma with total naevus count and a history of dysplastic naevi: a cross-sectional retrospective study within an academic centre.

BACKGROUND: High naevus count (HNC) (≥ 50 naevi) and presence of dysplastic naevi (DN) are risk factors for malignant melanoma (MM); however, MMs also occur in patients with low naevus count (LNC) (< 50 naevi) and in patients without DN. Little is known about differences between MMs in these groups. AIM: To characterize the clinicopathological differences between MMs in patients with HNC and those in patients with LNC, with or without biopsy-proven DN. METHODS: This was a cross-sectional retrospective chart review of 281 patients with MM seen between April 2013 and March 2014 at an academic pigmented lesion clinic (Boston, MA, USA). RESULTS: Patients with LNC MMs were diagnosed at an older age (51 vs. 41 years, P < 0.001, OR = 0.95, 95% CI 0.93-0.97), with more aggressive MM features, including greater Breslow thickness (1.1 vs. 0.8 mm, P = 0.01), more mitoses (2 vs. 1 mitoses/mm2 , P < 0.001), lower rate of superficial spreading subtype (58 vs. 78%, P < 0.01, OR = 2.57, 95% CI 1.31-5.03) and higher MM stage (P < 0.001), compared to patients with HNC. Patients with DN had similar trends as those in patients with HNC described above, and in addition, were more likely to have a truncal MM (55 vs. 39%, P < 0.01, OR = 1.97, 95% CI 1.22-3.18) with less ulceration (13 vs. 29%, P < 0.01, OR = 0.36, 95% CI 0.19-0.71). Patients without DN were more likely to have a history of a non-MM skin cancer (32 vs. 19%, P = 0.01, OR = 0.49, 95% CI 0.28-0.85) and an amelanotic MM (33 vs 21%, P = 0.03, OR = 0.55, 95% CI 0.31-0.96). CONCLUSIONS: Patients with LNC may develop MMs with more aggressive features at an older age than patients with HNC. A history of biopsy-proven DN reveals distinct MM differences compared to patients without DN.

[Signaling pathway of M2-type polarization induced by Mycobacterium tuberculosis-specific peptide E7 in monocyte-macrophages].

Objective: To explore the signal pathway of M2-type polarization induced by Mycobacterium tuberculosis (MTB)-specific peptide E7. Methods: Monocyte-macrophages were divided into blank control group, M1 positive stimulus group [co-stimulated with lipopolysaccharide and gamma interferon (IFN-γ)], M2 positive group(co-stimulated with IL-4 and IL-13), and E7 experimental group (with MTB-specificity polypeptide E7 stimulated). The expression of M1 type markers CD(16), IL-6, TNF-α and M2 type markers CD(163), CD(206), IL-10 were detected at 12, 18, 24 and 36 h. Furthermore, peroxisome proliferators-activated receptors-γ (PPAR-γ) blocker was used in the blank control group, M2-positive stimulus group and E7 experimental stimulus group. T test was used to compare the expression of PPAR-γ and CD(163) before and after the addition of blockers. Results: Compared with the positive control group and the blank control group, the expression of TNF-α in the E7 experimental group gradually reached the peak when macrophages were stimulated for 18 h(the relative expression was 20.02), and then the expression of TNF-α gradually decreased and the expression of CD(163) increased. The expression of CD(163) peaked at 24 h (the relative expression was 2.44). After adding the inhibitor, the expression of PPAR-γ in E7 stimulation group was lower than before blocking (before blocking 0.94±0.06, after blocking 0.69±0.09, P=0.028). CD(163) expression level was significantly lower than that before blocking (before blocking 3.95±0.61, after blocking 2.87±0.20, P=0.047). Conclusion: The MTB-specific peptide E7 induced differentiation of macrophages into M2 type, a process that may be involving PPAR-γ in just another kinase-signal transducer and activator of transcription pathway.

Effects of Surface Electron Doping and Substrate on the Superconductivity of Epitaxial FeSe Films.

Superconductivity in FeSe is greatly enhanced in films grown on SrTiO3 substrates, although the mechanism behind remains unclear. Recently, surface potassium (K) doping has also proven able to enhance the superconductivity of FeSe. Here, by using scanning tunneling microscopy, we compare the K doping dependence of the superconductivity in FeSe films grown on two substrates: SrTiO3 (001) and graphitized SiC (0001). For thick films (20 unit cells (UC)), the optimized superconducting (SC) gaps are of similar size (∼9 meV) regardless of the substrate. However, when the thickness is reduced to a few UC, the optimized SC gap is increased up to ∼15 meV for films on SrTiO3, whereas it remains unchanged for films on SiC. This clearly indicates that the FeSe/SrTiO3 interface can further enhance the superconductivity, beyond merely doping electrons. Intriguingly, we found that this interface enhancement decays exponentially as the thickness increases, with a decay length of 2.4 UC, which is much shorter than the length scale for relaxation of the lattice strain, pointing to interfacial electron-phonon coupling as the likely origin.

[Clinical features of neurosyphilis with optic neuritis as an initial finding].

Objective: To study the characteristics of neurosyphilis with optic neuritis as an initial finding. Methods: Retrospective analysis of clinical data and laboratory testing results of 16 cases (27 eyes) with optic neuritis as an initial finding of neurosyphilis from October 2010 to March 2015 in General Hospital of People's Liberation Army was made. Results: Six-teen patients (12 males, 4 females) were collected, the median age of patients was 47 (range 33 to 65) years ,the mean age was (49.63±9.05) years. Treponema pallidum particle agglutination assay (TPPA) analysis was positive in all of the patients and rapid plasma reagin (RPR) test was positive in 14 patients (2 patients did not test). Lumbar puncture was requested and performed for all patients. Cerebrospinal fluid (CSF) TPPA analysis was positive in 16 patients and RPR test was positive in 12 patients. The CSF white blood cell counting increased in 9 (56.3%) patients and 10(62.5%)patients presented with increased CSF protein level. Both eyes were involved in 11 patients (68.8%). Relative afferent papillary defect was positive in 11 patients. Twenty-seven eyes were affected in 16 patients, and among them 7 eyes' pupil diameter were 2.5 mm or less. Incipient visual acuity was less than 0.1 in 22 eyes. The slit lamp examination showed vitreous opacity in 12 eyes and visible cells in 6 eyes among 27 eyes. Fundus examination found that 6 eyes had papillary edema and 15 eyes had pallordisc among 27eyes. Electro-retinogram (ERG) was tested in 24 eyes, and 18 eyes were abnormal. Visual evoked potential (VEP) were performed in 26 eyes (flash VEP in 22 eyes, pattern VEP in 4 eyes), and all were abnormal. Fourteen eyes were tested by 30-2 perimetry, and 6 eyes had diffuse visual field defect, 2 eyes had peripheral visual field defect, 4 eyes had quadrant defect and 2 eyes had center scotoma. Fundus fluorescence angiography was done in 16 eyes and choroidal hyper-fluorescent dots were found in posterior pole in 4 eyes. All patients were treated with antibiotic medicines, among them 10 cases in the General Hospital, and 6 cases in the other hospitals. During 15 months follow-up after discharge, visual acuity of 17 eyes recovered to 0.5 and above. Conclusion: Syphilitic optic neuritis is a condition that manifests with severe visual loss and tends to involve both eyes, Some patients have a smaller pupil diameter. Due to the particular infective routes of the disease, patients often conceal their sexual history. The manifestations of ocular syphilis are complicated and easy to misdiagnose or undiagnose. Clinical manifestations combining with the detailed history taking, serum and cerebrospinal fluid examination can guide to an accurate diagnosis and prevent from permanent vision loss. (Chin J Ophthalmol, 2016, 52: 898-904).

Characteristics associated with the consumption of malted drinks among Malaysian primary school children: findings from the MyBreakfast study.

BACKGROUND: The consumption of beverages contributes to diet quality and overall nutrition. Studies on malted drinks, one of the widely consumed beverage choices among children in Asia, however, have received limited attention. This study aimed to examine the prevalence of malted drink consumption and explored associations of sociodemographic characteristics, nutrient intakes, weight status and physical activity levels with malted drink consumption among primary school children in Malaysia. METHODS: Data for this analysis were from the MyBreakfast Study, a national cross-sectional study conducted from April to October 2013 throughout all regions in Malaysia. A total of 2065 primary school children aged 6 to 12 years were included in the present analysis. Data on two days 24-h dietary recall or record, anthropometry, physical activity and screen time were recorded. Associations between malted drink consumption and related factors were examined using binary logistic regression, adjusting for region, area, gender, ethnicity and household income. RESULTS: Among children aged 6 to 12 years, 73.5% reported consuming malted drinks for at least once per week. Consumption of malted drinks was significantly associated with region (χ(2) = 45.64, p < 0.001), gender (χ(2) = 4.41, p = 0.036) and ethnicity (χ(2) = 13.74, p = 0.008). Malted drink consumers had similar total energy intake but higher micronutrient intakes compared to non-consumers. High physical activity level (OR = 1.77, 95% CI = 1.06, 2.99) and lower screen time during weekends (OR = 0.93, 95% CI = 0.86, 0.99) were independently associated with malted drink consumption among 6 to 9 year-old children, but not among 10 to 12 year-old children. No association was observed between malted drink consumption and weight status. CONCLUSIONS: Malted drink consumption is prevalent among Malaysian primary school children, particularly higher among boys, indigenous children and those who lived in the East Coast region of Malaysia. Consuming malted drinks is associated with higher micronutrient intakes and higher levels of physical activity, but not with body weight status.

A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma.

BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.