[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.

[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.

[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.

A systematic review of factors influencing attitudes towards and intention to use the long-distance caregiving technologies for older adults.

PURPOSE: Long-distance caregiving (LDC) technologies play a significant role in enabling distant care and facilitating living-alone older adults to keep socially connected. However, there is scarce research exploring the older adults' attitudes towards and intention to use such technologies. This paper is based on a systematic review of existing literature to explore the multifarious factors influencing independent community-living older adults' attitudes towards and intention to use LDC technologies. METHODS: Articles published in English between 2006 and 2020 were reviewed by searching electronic databases of PubMed, ProQuest, EBSCOhost. The inclusion criteria were limited to quantitative, qualitative, or mixed-methods studies that involved: 1) distant caregiving; 2) older adults aged 60 years or above, who were living alone or with only their spouse in the community (even though the samples might also involve other non-older adults); 3) technologies including ICT-based devices, systems, or programs enabling data transmission were used; 4), intention to use or behavioral usage in regard to the technologies were reported or discussed. RESULTS: In total, 41 out of 8674 articles were included. Both determinants and moderators of affecting the use of the ICT-based LDC technologies were identified with theoretical guidance. To summarize, there are personal factors involved, such as personality, concerns regarding security and privacy, health conditions, requisite knowledge, financial conditions, and influence from significant others, encompassing formal and informal caregivers; and factors related to the devices, in terms of their user-friendliness and functionality. CONCLUSION: This review highlights the importance of striking a good balance between functionality and privacy concerns, besides considering the direct and indirect cost to users. LDC technology education should be promoted at the societal level to facilitate older adults' better understanding of the device utilities by enhancing their technological literacy. Implications for various stakeholders to cope with the challenges of an aging population are also discussed.

ABO-Incompatible Living-Donor Kidney Transplantation in a Developing Country: A Multicenter Experience in Malaysia.

Malaysia has a low deceased-donor donation rate and has not embarked on a paired kidney exchange program; therefore, ABO-incompatible and HLA-incompatible transplantation remain the main contributor to the sustainability of the national kidney transplantation (KT) program. There were 26 cases of ABO-incompatible KTs performed from 2011 to 2018 in 3 major transplant centers, namely, Hospital Kuala Lumpur, University Malaya Medical Centre, and Prince Court Medical Centre. We collected perioperative and follow-up data through June 2019. The desensitization protocol varies and is center specific: the localized Japanese protocol and Swedish protocol with a target anti-A/B isoagglutinin titer of 16 or 32 on the day of transplant. The induction and tacrolimus-based maintenance protocol was nearly identical. The median follow-up time was 62.3 months (interquartile range, 37.0-79.7). Fifteen subjects had the highest predesensitization anti-A/B titer of ≥32 (57.7%). The acute cellular rejection and antibody-mediated rejection incidence were 12.5% (3 cases) and 8.3% (2 cases), respectively. Patient, graft, and death-censored graft survival rates were 96.2%, 92.3%, and 96.0%, respectively, 1 year post-living-donor KT (LDKT) and 96.2%, 87.2%, and 90.7%, respectively, 5 years post-LDKT. Our experience shows that ABO-incompatible LDKT using a suitable desensitization technique could be a safe and feasible choice for LDKT even with varied desensitization regimens for recipients with relatively high baseline isoagglutinin titers.

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.

Factors associated with fear of cancer recurrence in breast and colorectal cancer survivors: A cross-sectional study of cancer survivors.

AIM: To define the prevalence and severity of fear of cancer recurrence and identify factors associated with fear of cancer recurrence in breast cancer and colorectal cancer survivors attending the Sydney Cancer Survivorship Clinic. METHODS: A cross-sectional study was performed using prospectively collected data. Survivors completed questionnaires assessing quality of life (Functional Assessment of Cancer Therapy-General and symptoms (Distress Thermometer, Patient's Disease and Treatment Assessment Form)). Survivors were assessed by a clinical psychologist for the presence of fear of cancer recurrence. Clinical and quality of life variables were evaluated for associations with fear of cancer recurrence. RESULTS: Overall, 315 survivors (181 breast cancer, 134 colorectal cancer) were included. In total, 201 survivors (64%) had fear of cancer recurrence according to psychology assessment, and of the 118 that had fear of cancer recurrence severity recorded, 64 (54%) were rated as moderate-severe. On univariate analysis, fear of cancer recurrence was associated with younger age (P < 0.001), higher distress thermometer score (P = 0.001) and poorer overall wellbeing (P < 0.001). On multivariate analysis, younger age (P = 0.043), being bothered by side effects of treatment (P = 0.023), feeling sad (P = 0.020) and greater worry that their condition will get worse (P = 0.017) were independently associated with fear of cancer recurrence. CONCLUSIONS: Fear of cancer recurrence is common in breast and colorectal cancer survivors, and moderate-severe in over half. Fear of cancer recurrence was independently associated with younger age, feeling sad, being more bothered by side effects.

[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.

[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.

A Cost-Effective Alternative for Lateral Femoral Wall Perforation in Anterior Cruciate Ligament (ACL) Reconstruction: A Case Report.

Lateral femoral wall perforation is a rare intra-operative complication in anterior cruciate ligament (ACL) reconstruction surgery. However, it can be challenging to manage if it occurs. We share our experience on lateral femoral wall perforation managed by a large fragment washer. A 25-year-old man with right ACL injury presented with knee instability despite physiotherapy. Anterior drawer test (ADT) and Lachman test were grade 3, glide on pivot shift was positive. During ACL reconstruction, the lateral femoral wall was perforated. Due to unavailability of the rescue endobutton and budget constraint, we passed the endobutton through a washer and allowed it to sit on the washer over the lateral femoral wall. ADT and Lachman test on post-operative 6, 12 and 24 weeks were grade 1, with a negative pivot shift test. Lysholm knee score improved from 69 pre-operatively to 98 post-operatively. Conventionally, lateral femoral wall perforation can be managed by rescue endobutton, or screw and washer post technique. As this complication is rare, the rescue endobutton may not be available at all times, and the cost of the implant is also another important factor to consider. A washer can be used as an alternative technique to manage lateral femoral wall perforation in ACL reconstruction as it is not only cost-effective but also provides stable fixation with good functional outcome.

[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.

[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.

[Epidemiological analysis of pathogens causing bloodstream infections in department of hematology in Guangdong Province].

Objective: To evaluate the epidemiology of bacterial bloodstream infections in patients submitted to hematologic wards in southern China. Methods: A total of 50 teaching hospitals were involved based on the China Antimicrobial Resistance Surveillance System. The data of clinical isolates from blood samples were collected from January 1, 2019, to December 31, 2019. Antimicrobial susceptibility testing was conducted by the Kirby-Bauer automated systems, and the results were interpreted using the CLSI criteria. Results: The data of 1,618 strains isolated from hematologic wards in 2019 were analyzed, of which gram-negative bacilli and gram-positive cocci accounted for 71.8% and 28.2%, respectively. Of those, the five major species were most often isolated, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, coagulase-negative staphylococcus, and Streptococcus viridans. The prevalence rates of methicillin-resistant strains in Staphylococcus aureus and coagulase-negative staphylococcus were 19.7% and 80.6%, respectively. No gram-positive cocci were resistant to vancomycin, linezolid, and teicoplanin, and none of the enterococci were resistant to linezolid. The resistance rate of S. viridans to penicillin G was 6.9%, and those to ceftriaxone and cefotaxime were more than 25%. The resistance rate of E. coli and K. pneumoniae in Enterobacteriaceae was higher in children than that in adults. The resistance rate of K. pneumoniae to meropenem was 14.1%. The resistant rate of Enterobacter cloacae to carbapenem was more than 25%. P. aeruginosa was more sensitive to more antibiotics than 80%, but the resistance rate to meropenem in children was higher than that in adults (11.8% vs. 6.5%). The proportion of gram-positive cocci in the ICU and respiratory departments was higher than that in the hematology department. The detection rates of carbapenem-resistant E. coli and K. pneumoniae in the respiratory department were the lowest with 0.3% and 3.7%, respectively, while those of CRPA and CRAB in the hematology department were the lowest with 8.3% and 25.8%, respectively. The detection rate of all carbapenem-resistant organisms in the ICU was the highest among the three departments. Conclusion: The etiology and drug resistance of bacteria from blood samples in the hematology department are different from those in the ICU and respiratory departments. The proportions of K. pneumoniae, P. aeruginosa, E. cloacae, and S. viridans dominating in the department of Hematology were significantly higher than those in the ICU and respiratory departments in Guangdong region.

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.

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.

[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.

Periventricular White Matter Abnormalities on Diffusion Tensor Imaging of Postural Instability Gait Disorder Parkinsonism.

BACKGROUND AND PURPOSE: Postural instability gait disorder is a motor subtype of Parkinson disease associated with predominant gait dysfunction. We investigated the periventricular white matter comprising longitudinal, thalamic, and callosal fibers using diffusion tensor MR Imaging and examined clinical correlates in a cohort of patients with Parkinson disease and postural instability gait disorder and healthy controls. MATERIALS AND METHODS: All subjects underwent the Tinetti Gait and Balance Assessment and brain MR imaging. The DTI indices (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) from ROIs dropped over the superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, anterior thalamic radiation, anterior and posterior limbs of the internal capsule, and the genu and body of corpus callosum were evaluated. RESULTS: Our findings showed that the superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, genu of the corpus callosum, and body of the corpus callosum are more affected in postural instability gait disorder than in those with Parkinson disease or healthy controls, with more group differences among the longitudinal fibers. Only the callosal fibers differentiated the postural instability gait disorder and Parkinson disease groups. DTI measures in the superior longitudinal fasciculus, frontostriatal fibers (anterior thalamic radiation, anterior limb of the internal capsule), and genu of the corpus callosum fibers correlated with clinical gait severity. CONCLUSIONS: Findings from this case-control cohort lend further evidence to the role of extranigral pathology and, specifically, the periventricular fibers in the pathophysiology of postural instability gait disorder.