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.

[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.

Discovery and validation of vascular endothelial growth factor (VEGF) pathway polymorphisms in esophageal adenocarcinoma outcome.

Polymorphisms in the vascular endothelial growth factor (VEGF)/angiogenesis pathway have been implicated previously in cancer risk, prognosis and response to therapy including in esophageal adenocarcinoma. Prior esophageal adenocarcinoma studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new VEGF pathway polymorphisms associated with esophageal adenocarcinoma prognosis and validated them in an independent cohort of esophageal adenocarcinoma patients. In 231 esophageal adenocarcinoma patients of all stages/treatment plans, 58 genetic polymorphisms (18 KDR, 7 VEGFA and 33 FLT1) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then validated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median OS and PFS were 20 and 12 months, respectively. KDR rs17709898 was found significantly associated with PFS (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). FLT1 rs3794405 and rs678714 were significantly associated with OS (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No VEGFA polymorphisms were found significantly associated with either outcome. Upon validation, FLT1 rs3794405 remained strongly associated with OS (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). FLT1 rs3794405 is significantly associated with OS in esophageal adenocarcinoma, whereby each variant allele confers a 45-60% increased risk of mortality. Validation and evaluation of this association in other cancer sites are warranted.

Discovery of clinical isolation of drug-resistant Klebsiella pneumoniae with overexpression of OqxB efflux pump as the decisive drug resistance factor.

Background emergence of multidrug-resistant (MDR) bacterial strains is a public health concern that threatens global and regional security. Efflux pump-overexpressing MDR strains from clinical isolates are the best subjects for studying the mechanisms of MDR caused by bacterial efflux pumps. A Klebsiella pneumoniae strain overexpressing the OqxB-only efflux pump was screened from a clinical strain library to explore reverse OqxB-mediated bacterial resistance strategies. We identified non-repetitive clinical isolated K. pneumoniae strains using a matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrometry clinical TOF-II (Clin-TOF-II) and susceptibility test screening against levofloxacin and ciprofloxacin. And the polymorphism analysis was conducted using pulsed-field gel electrophoresis. Efflux pump function of resistant strains is obtained by combined drug sensitivity test of phenylalanine-arginine beta-naphthylamide (PaßN, an efflux pump inhibitor) and detection with ethidium bromide as an indicator. The quantitative reverse transcription PCR was performed to assess whether the oqxB gene was overexpressed in K. pneumoniae isolates. Additional analyses assessed whether the oqxB gene was overexpressed in K. pneumoniae isolates and gene knockout and complementation strains were constructed. The binding mode of PaßN with OqxB was determined using molecular docking modeling. Among the clinical quinolone-resistant K. pneumoniae strains, one mediates resistance almost exclusively through the overexpression of the resistance-nodulation-division efflux pump, OqxB. Crystal structure of OqxB has been reported recently by N. Bharatham, P. Bhowmik, M. Aoki, U. Okada et al. (Nat Commun 12:5400, 2021, https://doi.org/10.1038/s41467-021-25679-0). The discovery of this strain will contribute to a better understanding of the role of the OqxB transporter in K. pneumoniae and builds on the foundation for addressing the threat posed by quinolone resistance.IMPORTANCEThe emergence of antimicrobial resistance is a growing and significant health concern, particularly in the context of K. pneumoniae infections. The upregulation of efflux pump systems is a key factor that contributes to this resistance. Our results indicated that the K. pneumoniae strain GN 172867 exhibited a higher oqxB gene expression compared to the reference strain ATCC 43816. Deletion of oqxB led a decrease in the minimum inhibitory concentration of levofloxacin. Complementation with oqxB rescued antibiotic resistance in the oqxB mutant strain. We demonstrated that the overexpression of the OqxB efflux pump plays an important role in quinolone resistance. The discovery of strain GN 172867 will contribute to a better understanding of the role of the OqxB transporter in K. pneumoniae and promotes further study of antimicrobial resistance.

Viral shedding pattern of severe fever with thrombocytopenia syndrome virus in severely ill patients: A prospective, Multicenter cohort study.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is spreading rapidly in Asia. The pathway of SFTS virus shedding from patient and specific use of personal protective equipments (PPEs) against viral transmission have rarely been reported. The study was to determine SFTS virus (SFTSV) shedding pattern from the respiratory, digestive and urinary tract to outside in patients. Methods: Patients were divided into mild and severe groups in three sentinel hospitals for SFTS in Anhui province from April 2020 to October 2022. SFTSV level from blood, throat swabs, fecal/anal swabs, urine and bedside environment swabs of SFTS patients were detected by qRT-PCR. Specific PPEs were applied in healthcare workers contacting with the patients who had oropharyngeal virus shedding and hemorrhagic signs. Results: A total of 189 SFTSV-confirmed patients were included in the study, 54 patients died (case fatality rate, 28.57 %). Positive SFTSV in throat swabs (T-SFTSV), fecal/anal swabs (F-SFTSV) and urine (U-SFTSV) were detected in 121 (64.02 %), 91 (48.15 %) and 65 (34.4 %) severely ill patients, respectively. The levels of T-SFTSV, F-SFTSV and U-SFTSV were positively correlated with the load of SFTSV in blood. We firstly revealed that SFTSV positive rate of throat swabs were correlated with occurrence of pneumonia and case fatality rate of patients (P < 0.0001). Specific precaution measures were applied by healthcare workers in participating cardiopulmonary resuscitation and orotracheal intubation for severely ill patients with positive T-SFTSV, no event of SFTSV human-to-human transmission occurred after application of effective PPEs. Conclusions: Our research demonstrated SFTSV could shed out from blood, oropharynx, feces and urine in severely ill patients. The excretion of SFTSV from these parts was positively correlated with viral load in the blood. Effective prevention measures against SFTSV human-to-human transmission are needed.

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.

[Preparation of sub-standard samples and XRF analytical method of powder non-metallic minerals].

In order to solve the problem that standard samples of non-metallic minerals are not satisfactory in practical work by X-ray fluorescence spectrometer (XRF) analysis with pressed powder pellet, a method was studied how to make sub-standard samples according to standard samples of non-metallic minerals and to determine how they can adapt to analysis of mineral powder samples, taking the K-feldspar ore in Ebian-Wudu, Sichuan as an example. Based on the characteristic analysis of K-feldspar ore and the standard samples by X-ray diffraction (XRD) and chemical methods, combined with the principle of the same or similar between the sub-standard samples and unknown samples, the experiment developed the method of preparation of sub-standard samples: both of the two samples above mentioned should have the same kind of minerals and the similar chemical components, adapt mineral processing, and benefit making working curve. Under the optimum experimental conditions, a method for determination of SiO2, Al2O3, Fe2O3, TiO2, CaO, MgO, K2O and Na2O of K-feldspar ore by XRF was established. Thedetermination results are in good agreement with classical chemical methods, which indicates that this method was accurate.

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.

Synthesis of novel thiazolyl-pyrimidines and their anticancer activity in vitro.

A series of novel compounds 7-43 were prepared via the condensation of enaminones 4a-h and the guanidines carbonate 6a-f. The structures of these newly synthesized compounds were confirmed by (1) H-NMR, MS, EA and IR. All the compounds were tested for their cytotoxic activity in vitro against human cancer cell lines including Ishikawa, A549, BEL-7404, SPC-A-01 and SGC-7901. Most of them showed moderate cytotoxic against the tested cell lines. Among them, the most potent compounds 9 and 30 exhibited more efficient activity against Ishikawa, A549.

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.

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.

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.

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.

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.

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.

Development and application of a novel and effective screening method for aerobic denitrifying bacteria.

Herein we describe a novel and effective screening method for aerobic denitrifying bacteria. For this procedure, we utilized KCN to inhibit the electron transference from Cytaa3 to oxygen in the bacteria respiratory chain. We employed a 3-h aeration operation cycle and intermittent rotations. The resultant bacterial suspensions were plated on a KCN-screening medium and incubated aerobically. Single colonies were selected and incubated in an aerobic culture medium. Culture nitrate and nitrite levels were determined over time, and ultimately four bacterial strains that performed denitrifying under aerobic conditions were identified by this method. Of these, strain Y2-1-1 demonstrated the best aerobic denitrifying ability. In a 5-day test, the NO3--N of the aerobic culture medium was reduced from 282.0+/-8.3 mg L(-1) to 149.2+/-17.1 mg L(-1), with little nitrite or N2O production. The morphological, physiological and biochemical characteristics and the 16S rRNA gene sequence homology comparison data for this strain were consistent with the classification of the genus Pseudomonas. We named this strain Pseudomonas sp. Y2-1-1.