Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1ß production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

LPS-aggravated Ferroptosis via Disrupting Circadian Rhythm by Bmal1/AKT/p53 in Sepsis-Induced Myocardial Injury.

Circadian disruption is involved in the progress of sepsis-induced cardiomyopathy (SICM), one of the leading causes of death in sepsis. The molecular mechanism remains ambiguous. In this study, LPS was used to build SICM model in H9c2 cell. The results suggested that LPS induced cytotoxicity via increasing ferroptosis over the time of course. After screening the expressions of six circadian genes, the circadian swing of Bmal1 was dramatically restrained by LPS in H9c2 cell of SIMC vitro model. PcDNA and siRNA were used to upregulate and downregulate Bmal1 and confirmed that Bmal1 inhibited LPS-triggered ferroptosis in H9c2 cells. Then, the results suggested that AKT/p53 pathway was restrained by LPS in H9c2 cell. Rescue test indicated that Bmal1 inhibited LPS-triggered ferroptosis via AKT/p53 pathway in H9c2 cells. In summary, our findings demonstrated that LPS induced cytotoxicity via increasing ferroptosis over the time of course in H9c2 cells and Bmal1 inhibited this toxicity of LPS via AKT/p53 pathway. Although further studies are needed, our findings may contribute to a new insight to mechanism of SICM.

Phosphoethanolamine cytidylyltransferase ameliorates mitochondrial function and apoptosis in hepatocytes in T2DM in vitro.

Liver function indicators are often impaired in patients with type 2 diabetes mellitus (T2DM), who present higher concentrations of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase than individuals without diabetes. However, the mechanism of liver injury in patients with T2DM has not been clearly elucidated. In this study, we performed a lipidomics analysis on the liver of T2DM mice, and we found that phosphatidylethanolamine (PE) levels were low in T2DM, along with an increase in diglyceride, which may be due to a decrease in the levels of phosphoethanolamine cytidylyltransferase (Pcyt2), thus likely affecting the de novo synthesis of PE. The phosphatidylserine decarboxylase pathway did not change significantly in the T2DM model, although both pathways are critical sources of PE. Supplementation with CDP-ethanolamine (CDP-etn) to increase the production of PE from the CDP-etn pathway reversed high glucose and FFA (HG&FFA)-induced mitochondrial damage including increased apoptosis, decreased ATP synthesis, decreased mitochondrial membrane potential, and increased reactive oxygen species, whereas supplementation with lysophosphatidylethanolamine, which can increase PE production in the phosphatidylserine decarboxylase pathway, did not. Additionally, we found that overexpression of PCYT2 significantly ameliorated ATP synthesis and abnormal mitochondrial morphology induced by HG&FFA. Finally, the BAX/Bcl-2/caspase3 apoptosis pathway was activated in hepatocytes of the T2DM model, which could also be reversed by CDP-etn supplements and PCYT2 overexpression. In summary, in the liver of T2DM mice, Pcyt2 reduction may lead to a decrease in the levels of PE, whereas CDP-etn supplementation and PCYT2 overexpression ameliorate partial mitochondrial function and apoptosis in HG&FFA-stimulated L02 cells.

BAF60a Deficiency in Macrophage Promotes Diet-Induced Obesity and Metabolic Inflammation.

Adipose tissue macrophage (ATM) has been shown to play a key role in the pathogenesis of obesity-associated adipose tissue inflammation and metabolic diseases. However, the upstream factors that integrate the environmental signals to control ATM activation and adipose inflammation in obesity remain elusive. Here, we identify BAF60a, a subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin remodeling complexes, as the central checkpoint regulator of obesity-induced ATM activation, adipose tissue inflammation, and systemic metabolic impairment. BAF60a expression was robustly downregulated in the adipose tissue stromal vascular fractions in type 2 diabetic mice. Myeloid-specific BAF60a knockout (BaMKO) promotes ATM proinflammatory activation, exacerbating diet-induced obesity, insulin resistance, and metabolic dysfunction. Conversely, myeloid-specific overexpression of BAF60a in mice attenuates macrophage proinflammatory activation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate that BAF60a inactivation triggers the expression of proinflammatory gene program through chromatin remodeling. Moreover, motif analysis of ATAC-Seq and CUT&Tag-Seq data identifies the transcription factor Atf3 that physically interacts with BAF60a to suppress the proinflammatory gene expression, thereby controlling ATM activation and metabolic inflammation in obesity. Consistently, myeloid-specific Atf3 deficiency also promotes the proinflammatory activation of macrophage. This work uncovers BAF60a/Atf3 axis as the key regulator in obesity-associated ATM activation, adipose tissue inflammation, and metabolic diseases.

Blockade of platelet glycoprotein receptor Ib ameliorates blood-brain barrier disruption following ischemic stroke via Epac pathway.

Glycoprotein (GP) Ib is a platelet membrane receptor complex exposed to vascular injury, proposed as an effective target for stroke therapy. Previously, we have observed that the GPIb antagonist anfibatide (ANF) could mitigate blood-brain barrier (BBB) disruption following cerebral ischemia/reperfusion (CI/R) injury. The current study was designed to investigate whether the amelioration of the BBB by ANF is mediated via the Epac signaling pathway. A murine model of CI/R injury was induced following 90 min of transient middle cerebral artery occlusion (MCAO). ANF (4 µg/kg) was intravenously injected 1 h after reperfusion. Herein, ANF ameliorated BBB disruption, increased the expression of tight junction proteins, suppressed F-actin cytoskeleton rearrangement, decreased the permeability of the ischemic brain tissue, and relieved brain edema. ANF-treated mice had smaller infarct volumes and less severe neurological deficits than the MCAO mice. Moreover, the effects of ANF and Epac1 agonists were very similar in the MCAO mice. Epac activation with a cAMP analog, 8-CPT-2'-O-Me-cAMP, mitigated the breakdown of BBB function and CI/R injury. The Epac specific antagonist, ESI-09, worsened barrier damage and cerebral impairment, antagonizing the protective effects afforded by ANF. In addition, ANF upregulated the expression of Epac1 protein in the ischemic cerebral cortex. Collectively, our results indicate that the protective effect of ANF on the BBB after CI/R could be attributed to the activation of the Epac pathway.

Characteristics of pediatric inpatients with primary and secondary hypertension.

IMPORTANCE: Extensive population-based studies have explored the prevalence of primary hypertension (HTN) in children and adolescents. However, there is little published data on the characteristics of different types of pediatric HTN and the causes of secondary HTN. OBJECTIVE: To investigate the characteristics of different types of pediatric HTN and the causes of secondary HTN in a hospital setting. METHODS: The study cohort comprised pediatric inpatients (<18 years of age) discharged with a diagnosis of HTN from Beijing Children's Hospital during 2015-2020. Pediatric patients with HTN were allocated to secondary and primary HTN groups on the basis of comprehensive analyses of their diagnoses, family history of HTN, and findings on physical examination, as documented in their medical records. The Mann-Whitney U test, χ 2 and Fisher's exact test were used to assess differences in characteristics of patients with different HTN types and causes of secondary HTN. RESULTS: Data of 1470 inpatients with HTN from 18 clinical departments were included in the analysis. Among them, 458 (31.2%) had primary HTN, and 1012 (68.8%) had secondary HTN. Compared with patients had primary HTN, children with secondary HTN were younger and had lower body mass indexes and longer lengths of stay. Moreover, children with primary HTN had mostly been managed by the Endocrinology and Cardiology Departments, 75.8% of them having obesity-related comorbidities. In contrast, most patients with secondary HTN had been managed by the Nephrology Department, renal diseases being the leading cause of their HTN (46.3%). INTERPRETATION: Secondary HTN is more common than primary HTN in pediatric clinical settings, renal diseases being the leading cause of secondary HTN.

Preoperative planning by osteotomy master software helps to improve the accuracy of target limb alignment in high tibial osteotomy.

BACKGROUND: The accuracy of targeted lower limb alignment correction following HTO is closely related to patients' pain relief and knee joint survival time. How to accurately perform osteotomy and how to obtain the ideal target limb alignment to maximize the curative effect are the difficulty in HTO practice. The purpose of this study is to evaluate the predictive and application value of osteotomy master software (OsteoMaster) in coronal plane preoperative planning of high tibial osteotomy. METHOD: Sixty-seven patients with medial compartment osteoarthritis and varus deformity treated by medial open-weight high tibial osteotomy were enrolled and divided into observation group (31 cases) and control group (36 cases). The observation group was planned by OsteoMaster, while the control group was planned by Miniaci. The preoperative predicted values of osteotomy depth, open height, correction angle, WBL ratio, and FTA of the observation group were compared with the actual intraoperative values to study their accuracy. The operative time, blood loss, number of fluoroscopy, and WBL ratio were compared between the observation group and the control group to study its application value. RESULT: There was no significant difference between two groups in preoperative prediction and intraoperative reality of osteotomy depth, open height, correction angle, FTA, and WBL ratio (P > 0.05). The operation time and number of fluoroscopy in the observation group were significantly less than those in the control group (P < 0.05), while the difference in blood loss was not statistically significant (P > 0.05). The good rate of WBL ratio was 87.1% in the observation group and 75% in the control group. CONCLUSION: OsteoMaster has predictive value in osteotomy depth, open height, correction angle, FTA, and WBL ratio of HTO, which is also helpful to reduce the number of fluoroscopy, shorten the operation time, and improve the accuracy of target limb alignment. The drawback of this approach is 2-dimensional approach in contrast to 3-dimensional preoperative planning that is including the more real study.

Comparison between cervical disc arthroplasty and conservative treatment for patients with single level cervical radiculopathy at C5/6.

BACKGROUND: Cervical radiculopathy is a common disease that affects millions of people. Patients usually are managed by conservative therapy and surgical treatments. OBJECTIVE: To compare the clinical outcomes between cervical disc arthroplasty (CDA) and conservative management for patients with single level cervical radiculopathy at C5/6. METHODS: Seventy-two patients with cervical radiculopathy that only affect C5/6 joints were included and thirty-two of them received CDA surgery, and forty patients were treated with conservative management. All the patients were followed up around 4 years. Cervical curvature, cervical range of motion (CROM), horizontal displacement of cervical spine, and intervertebral gap were measured by radiological examination. RESULTS: All the patients have comparable disease severity based on pre-surgical radiological assessments. At the 4-year follow-up examination, patients with CDA surgery had less CROM at C5/6 level, while greater CROM at C4/5 level, than control group. Similarly, the horizontal displacement in CDA group decreased at C5/6 vertebrae, and increased at C4/5 level at the 4-year follow-up examination. The intervertebral gaps of patients in CDA group were larger than control group at one-year and last follow-up examination. CONCLUSION: CDA surgery stabilized C5/6 vertebrae and increased the CROM and horizontal displacement of upper adjacent C4/5 vertebrae.

The Regulation of Seventeen Inflammatory Mediators are Associated with Patient Outcomes in Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) as an emerging infection disease results in high morbidity and mortality in China. In this study, the circulating levels of 36 inflammatory mediators in 33 SFTS patients on days 3-7, 8-12 and 13-20 post-illness were measured by a multiplex Luminex® system dynamically. Among the patients, 15 severe patients recovered, 11 severe patients died within three weeks. We found IL-1RA, IL-6, IL-15, IL-10, TNF-α, IFN-γ, G-CSF, eotaxin, IL-8, IP-10, MCP-1, MIP-1α, MIP-1ß and fractalkine were significantly upregulated in SFTS patients. Elevated IL-15 and eotaxin in SFTS patients were reported firstly. The highest levels of pro-inflammatory and anti-inflammatory cytokines coexisted in fatal patients during the first week. Inflammatory mediators remained high levels when death occurred in fatal patients, they were recovered within three weeks in nonfatal patients. Our results showed the occurrence of inflammatory storm in SFTS patients were associated with the severity of SFTS. RANTES and PDGF were down regulated and remained significantly lower levels in fatal patients throughout the course of disease, the concentrations of RANTES and PDGF were remarkably positively correlated with the platelet count. Our results demonstrated that dysregulated inflammatory response was associated with disease pathogenesis and mortality in SFTS patients.

Lentivirus-mediated silencing of the CTGF gene suppresses the formation of glial scar tissue in a rat model of spinal cord injury.

BACKGROUND CONTEXT: One of the many reactive changes following a spinal cord injury (SCI) is the formation of a glial scar, a reactive cellular process whereby glial cells accumulate and surround the central nervous system injury sites to seal in the wound. Thus, the inhibition of glial scar is of great importance for SCI recovery. PURPOSE: This study aimed to explore the effect of lentivirus-mediated silencing of the CTGF gene on the formation of glial scar tissue in a rat model of SCI. STUDY DESIGN: This is a prospective study. STUDY SAMPLE: A total of 56 Wistar female rats aged 8 weeks were randomly selected for this study. OUTCOME MEASURES: The motor function of the rats was assessed using the Basso, Beattie, and Bresnahan (BBB) functional scale, footprint analysis of gait, and the Basso Mouse Scale (BMS). Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect the mRNA and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, and laminin in the spinal cord tissues. METHODS: A rat model of SCI was successfully established. Fifty-six male Wistar rats were randomly selected and assigned into four groups (14 rats in each group): the sham operation group, the SCI model group, the negative control (NC) group (SCI rats transfected with empty vector plasmids), and the siRNA-CTGF group (SCI rats transfected with lentivirus CTGF siRNA). RESULTS: The SCI rats showed decreased activity and were dragging their bodies while moving. Compared with the sham operation group, the BBB and BMS scores in the SCI model, NC, and siRNA-CTGF groups significantly decreased. However, the BBB and BMS scores in the siRNA-CTGF group were higher than those in the SCI model and NC groups. The mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin significantly increased in the SCI model, NC, and siRNA-CTGF groups in comparison with those in the sham operation group. Furthermore, the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin in the siRNA-CTGF group were lower than those in the SCI model and NC groups 28 days after transfection. CONCLUSIONS: These findings indicate that lentivirus-mediated silencing of the CTGF gene can suppress the formation of glial scar tissue after SCI.

Effect of the adenovirus­mediated Wip1 gene on lumbar intervertebral disc degeneration in a rabbit model.

The present study aimed to investigate the effect of the adenovirus­mediated wild­type p53­induced protein phosphatase 1 (Wip1) gene on lumbar disc degeneration (LDD) in a rabbit model. Adult New Zealand white rabbits were used as experimental subjects. The rabbits were divided into LDD groups (groups A­C of rabbit models of LDD) and control groups (groups D­F of normal rabbits). The animals in groups A and D were injected with the Wip1 gene vector, those in groups B and E were injected with an empty vector, and those in groups C and F were injected with phosphate­buffered saline. Type II collagen was detected using a streptavidin­biotin complex immunohistochemistry method. Postoperative X­ray imaging showed a significant increase in the recovery of rabbits from group A, compared with those from groups B and C. The nucleus pulposus proteoglycan content of the intervertebral discs (L2­3, L3­4 and L4­5) of group A remained higher, compared with the content in groups B and C, and the values in groups B and C differed from those of groups E and F. At 3, 6 and 9 weeks post­injection, the content of type II collagen of intervertebral discs (L2­3, L3­4 and L4­5) in group A differed from groups B and C, and the values in groups A­C remained lower, compared with those in groups D­F. The Wip1 gene exhibited a therapeutic effect in the treatment of LDD.

One-stage surgical treatment of cervical spine fracture-dislocation in patients with ankylosing spondylitis via the combined anterior-posterior approach.

The aim of the article is to investigate the efficacy and safety of 1-stage surgical therapy via combined anterior-posterior approach on cervical spine fracture in patients with ankylosing spondylitis (AS).We retrospectively analyzed profiles of 12 AS patients with severe fracture-dislocation of cervical spine received 1-stage combined anterior-posterior surgery in our hospital from October, 2013, to October, 2015, including clinical characteristics, follow-up data, and imaging records. We compared the parameters before and after surgery on the basis of neurological function, bone fusion, Cobb angles of operation segment, Barthel index (BI) score, and incidence rate of complications.A total of 12 patients received 1-stage surgery via combined anterior-posterior approach within 3 days after injury. No severe complications and death occurred. All patients received the successfully anatomical reduction of fracture-dislocation, in which 9 achieved function restoration. The latest follow-up showed the neurological function status of patients was improved. The Cobb angles of operation segments were recovered; the rate of bone fusion was 66.7% at 3 months and 100% at 6 months post-operation. The BI score was improved, 4 cases of moderate dependence and 8 of slight dependence at the latest follow-up compared to 10 of severe dependence and 2 of moderate dependence preoperation. In no cases did severe complications from implanted instrumentation occur.It was high efficacy and safety that the surgical therapy was performed on cervical fracture-dislocation in AS patients by the 1-stage combined anterior-posterior approach. The key of the surgery is the robust stabilization and full decompression of fracture spine at early stage. In addition, if spinal anatomical reduction of fracture segments is difficult to be achieved, the functional restoration should be adopted during the surgery.

Pretreatment quality-of-life score is a better discriminator of oesophageal cancer survival than performance status.

OBJECTIVES: Performance status [Eastern Cooperative Oncology Group (ECOG)] is a physician-assigned score indicating a patient's fitness for treatment. Functional assessment of cancer therapy-esophagus (FACT-E) is a patient-reported, health-related quality-of-life (HRQOL) instrument containing an oesophageal cancer subscale (ECS). Our objective was to assess the discriminative ability of pretreatment FACT-E and ECS when compared with performance status in predicting survival in patients with Stage II-III oesophageal cancer. METHODS: Patient data from four prospective studies were pooled together. These four studies included oesophageal patients who received chemoradiation either as neoadjuvant therapy or as definitive therapy. Three separate Cox regressions were performed considering FACT-E, ECS and ECOG as the main predictors, respectively. Receiver-operating characteristics analyses were performed. RESULTS: Of the 120 curative intent patients, 39.8% (n = 51), 58.6% (n = 75) and 1.6% (n = 2) had ECOG 0, 1 and 2, respectively. On Cox regression analysis, pretreatment FACT-E (P = 0.04) and ECS (P = 0.004) but not ECOG (P = 0.27) were independently associated with overall survival. ECOG could not discriminate between survivors and non-survivors (P = 0.28) with an area under the curve (AUC) of 0.56 [95% confidence interval (CI): 0.45-0.66], whereas FACT-E (P = 0.02) and ECS (P < 0.001) were discriminative with AUC = 0.63 (95% CI: 0.52-0.73) and AUC = 0.69 (95% CI: 0.60-0.79), respectively. CONCLUSIONS: In patients with Stage II-III oesophageal cancer being considered for curative therapy, pretreatment FACT-E and ECS have better discrimination for survival than does ECOG. The majority of patients were ECOG 0/1. Thus, these patient-derived scores were able to discriminate survivors from non-survivors even within this constrained range of clinician-assigned performance status. This highlights the potential utility of FACT-E and ECS as prognostic tools.

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.

Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8­week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

Recursive Partitioning Method on Competing Risk Outcomes.

In some cancer clinical studies, researchers have interests to explore the risk factors associated with competing risk outcomes such as recurrence-free survival. We develop a novel recursive partitioning framework on competing risk data for both prognostic and predictive model constructions. We define specific splitting rules, pruning algorithm, and final tree selection algorithm for the competing risk tree models. This methodology is quite flexible that it can corporate both semiparametric method using Cox proportional hazards model and parametric competing risk model. Both prognostic and predictive tree models are developed to adjust for potential confounding factors. Extensive simulations show that our methods have well-controlled type I error and robust power performance. Finally, we apply both Cox proportional hazards model and flexible parametric model for prognostic tree development on a retrospective clinical study on oropharyngeal cancer patients.

Increase in the Prevalence of Resistance Determinants to Trimethoprim/Sulfamethoxazole in Clinical Stenotrophomonas maltophilia Isolates in China.

AIMS: This study was carried to reveal the genetic mechanisms of trimethoprim/sulfamethoxazole (SXT) resistance. METHODS: Among 300 clinical Stenotrophomonas maltophilia isolates from China, resistance determinants such as sul and dfrA genes, integrons and transposase were examined using PCR, DNA sequencing and thermal asymmetric interlaced PCR (TAIL-PCR). Data were analyzed using SPSS 20.0. RESULTS: Of the 300 isolates, 116 (38.7%) were resistant to SXT. An alarming trend of increased resistance to SXT were found over the 10-year period. The positive rates of sul and class 1 integrase (intI1) increased gradually with the development of SXT resistance over the 10-year period. Multiple logistic regression analyses indicated that the genes of qacEΔ1-sul1 (81% vs 46.2%, p = 0.000), sul2 (50.9% vs 9.8%, p = 0.000), intI1 (83.6% vs 65.8%, p = 0.000), dfrA12 (25% vs 3.3%, p = 0.000), dfrA17 (15.5% vs 3.8%, p = 0.000) and dfrA27 (4.3% vs 1.6%, p = 0.01) were more prevalent in SXT-resistant isolates than SXT-susceptible isolates except dfrA1(p = 0.83) and dfrA5(p = 0.18). Sequencing data revealed 12 types of resistance gene cassettes (aar-3-dfrA27, dfrA12-aadA2, dfrA17-aadA5, cmlA1, aacA4, aadA5, arr-3-aacA4, aadA1, aadB-aadA4, aacA4-catB8-aadA1, aadB-aac(6')-II-blaCARB-8 and aac(6')-II-blaCARB-8) located in the class 1 integron in 163 isolates (87% SXT-resistant vs 33.7% SXT-susceptible isolates, p = 0.000). A novel finding was the aar-3-dfrA27 (KC748137) gene cassette. The gene of sul2 linked to transposase in 50 SXT- resistant and 7 SXT- susceptible isolates was detected by TAIL-PCR. CONCLUSIONS: The findings demonstrated a higher prevalence of sul, dfrA, intI1 and resistance gene cassettes in class 1 integron in SXT-resistant clinical S. maltophilia isolates in China. The sul1 and dfrA genes located in integrons and the sul2 linked to transposase may imply wide and rapid dissemination of resistance gene in bacteria.

The decreased expression of electron transfer flavoprotein ß is associated with tubular cell apoptosis in diabetic nephropathy.

Tubular injury is closely correlated with the development of progressive diabetic nephropathy (DN), particularly in cases of type 2 diabetes. The apoptosis of tubular cells has been recognized as a major cause of tubular atrophy, followed by tubulointerstitial fibrosis. Electron transfer flavoprotein ß (ETFß) is known as an important electron acceptor in energy metabolism, but its role in DN was not fully understood. In the present study, we examined the expression pattern of ETFß using diabetic kidney samples and further investigated ETFß involvement in tubular epithelial cell (TEC) apoptosis. Human renal biopsy specimens from patients with DN as well as a spontaneous rat model of diabetes using Otsuka Long-Evans Tokushima fatty (OLETF) rats, were employed in order to examine the expression of ETFß and cell apoptosis in kidneys during the development of DN (for the rats, at 36 and 56 weeks of age respectively). Moreover, ETFß siRNA was used to investigate the role of ETFß in the apoptosis of renal tubular cells. Our present results showed that the expression of ETFß in the kidneys was progressively decreased both in patients with DN and OLETF rats, which coincided with progressive renal injury and TEC apoptosis. In addition, the in vitro study demonstrated that knockdown of ETFß caused apoptosis in tubular cells, as proven by the increased expression of pro­apoptotic proteins and TUNEL assay. Therefore, the findings of our present study suggest that ETFß plays an important role in renal tubular cell apoptosis during the progression of DN.

Baseline measure of health-related quality of life (Functional Assessment of Cancer Therapy-Esophagus) is associated with overall survival in patients with esophageal cancer.

OBJECTIVE: Functional Assessment of Cancer Therapy-Esophagus is a health-related quality of life instrument validated in patients with esophageal cancer. It is composed of a general component and an esophageal cancer subscale. Our objective was to determine whether the baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores are associated with survival in patients with stage II and III cancer of the gastroesophageal junction or thoracic esophagus. METHODS: Data from 4 prospective studies in Canadian academic hospitals were combined. These included consecutive patients with stage II and III esophageal cancer who received neoadjuvant therapy followed by surgery or chemoradiation/radiation alone. All patients completed baseline Functional Assessment of Cancer Therapy-Esophagus. Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores were dichotomized on the basis of median scores. Cox regression analyses were performed. RESULTS: There were 207 patients treated between 1996 and 2014. Mean age was 61 ± 10.6 years. Approximately 69.6% of patients (n = 144) had adenocarcinoma. All patients had more than 9 months of follow-up. In patients with stage II and III, 93 deaths were observed. When treated as continuous variables, baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were associated with survival with hazard ratios of 0.89 (95% confidence interval [CI], 0.81-0.96; P = .005) and 0.68 (95% CI, 0.56-0.82; P < .001), respectively. When dichotomized, they were also associated with survival with a hazard ratio of 0.58 (95% CI, 0.38-0.89; P = .01) and 0.43 (95% CI, 0.28-0.67; P < .001), respectively. CONCLUSIONS: In patients with stage II and III esophageal cancer being considered for therapy, higher baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were independently associated with longer survival, even after adjusting for age, stage, histology, and therapy received. Further study is needed, but Functional Assessment of Cancer Therapy-Esophagus may be useful as a prognostic tool to inform patient decision-making and patient selection criteria for studies.

Impact of elective neck dissection on the outcome of oral squamous cell carcinomas arising in the maxillary alveolus and hard palate.

BACKGROUND: Whether elective lymph neck dissection (ELND) is associated with improved survival in oral squamous cell carcinomas (SCC) of the maxillary alveolus/hard palate is not known. METHODS: One hundred ninety-nine patients presenting de novo and receiving treatment for clinically node negative SCC of the maxillary alveolus/hard palate at 2 cancer centers between 1985 and 2011 were analyzed. RESULTS: Forty-two patients (21%) received ELND. Occult nodal metastases were present in 29% of the dissected necks. The ELND group had more T3 to T4 status tumors (62% vs 34%; p < .001) and positive-margin resections (59% vs 38%; p = .019). Patients undergoing ELND experienced lower rates of neck recurrence (6% vs 21%; p = .031), superior 5-year recurrence-free survival (68% vs 45%; p = .026), and overall survival (86% vs 62%; p = .043). ELND was associated with a 2-fold decrease in risk of recurrence in multivariable analysis. CONCLUSION: ELND was associated with lower rates of recurrence and improved survival in SCC of the maxillary alveolus/hard palate. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1688-E1694, 2016.

[Experimental study of Tangshen formulain improved lipid metabolism and phenotypic switch of macrophage in db/db mice].

Obesity and its associated metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), have become major chronic diseases threatening public health. NAFLD is a chronic liver disorder that is strongly associated with type 2 diabetes and obesity. In this study, we investigated the effects and mechanism of Tangshen formula (TSF) on hepatic dyslipidemia and phenotypic switch of macrophage in db/db mice. Eight-week-old male C57BLKS/J db/m control and db/db mice were divided into 3 groups (namely db/m, db/db, db/db+TSF), and fed with TSF or distilled water for 12 weeks. It was found that after treatment with TSF, the triglycerides accumulation in db/db mice was decreased on the basis of oil red O staining with cryosections of liver tissues. And protein expressions of macrophage activation markers CD68 and F4/80 were decreased according to immunohistochemical analysis of hepatic sections. The mRNA level of TNF-α (M1 marker) was significantly decreased by TSF in db/db mice, but with no significant difference in Mrc1 and Arg1 (M2 marker). According to the results, TSF attenuated hepatic steatosis and relieved dyslipidemia, its mechanism may be correlated with the regulation of macrophage activation and phenotypic switch.