Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus.

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Effects of adatom species on the structure, stability, and work function of adatom-α-borophene nanocomposites.

Work function-tunable borophene-based electrode materials are of significant importance because they promote efficient carrier extraction/injection, thereby enabling electronic devices to achieve maximum energy conversion efficiency. Accordingly, determining the work function of adatom-borophene nanocomposites within a series wherein the adatom is systematically changed will facilitate the design of such materials. In this study, we theoretically determined that the M-B bond length, binding energy, electron transfer between adatoms and BBP, and work function (ϕ) are linearly dependent on the ionization potential (IP) and electronegativity for thermodynamically and kinetically stable adatom-α-borophene (M/BBP) systems involving a series of alkali (earth) metal/BBP (M = Li-Cs; Be-Ba) and halogen/BBP (M = F-I), respectively. However, the binding energies of Li/BBP and Be/BBP deviate from these dependencies owing to their super small adatoms and the resulting significantly enhanced effective M-B bonding areas. By interpreting the electron transfer picture among the different parts of M/BBP, we confirmed that metallic M/BBP possesses ionic sp-p and dsp-p M-B bonds in alkali (earth) metal/BBP but covalent-featured ionic p-p interactions in halogen/BBP. In particular, the direct proportionality between IP and ϕ for alkali (earth) metal/BBP originates from the synergistic effect of charge rearrangement and the increased induced dipole moment; however, the inverse proportionality between electronegativity and ϕ for halogen/BBP arises from the adsorption induced charge redistribution. Our results provide guidance for experimental efforts toward the realization of work function-tunable borophene-based electrodes as well as insight into the bonding rules between various adatoms and α-borophene.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

Imparting α-Borophene with High Work Function by Fluorine Adsorption: A First-Principles Investigation.

Increasing the work function of borophene over a large range is crucial for the development of borophene-based anode materials for highly efficient electronic devices. In this study, the effect of fluorine adsorption on the structures and stabilities, particularly on the work function, of α-borophene (BBP), was systematically investigated via first-principles density functional theory. The calculations indicated that BBP was well-stabilized by fluorine adsorption and the work functions of metallic fluorine-adsorbed BBPs (Fn-BBPs) sharply increased with increasing fluorine content. Moreover, the work function of F-BBP was close to that of the frequently used anode material Au and even, for other Fn-BBPs, higher than that of Pt. Furthermore, we have comprehensively discussed the factors, including substrate deformation, charge transfer, induced dipole moment, and Fermi and vacuum energy levels, affecting the improvement of work function. Particularly, we have demonstrated that the charge redistribution of the substrate induced by the bonding interaction between fluorine and the matrix predominantly contributes to the observed increase in the work function. Additionally, the effect of fluorine adsorption on the increase in the work function of BBP was significantly stronger than that of silicene or graphene. Our results concretely support the fact that Fn-BBPs can be extremely attractive anode materials for electronic device applications.

Zinc as a countermeasure for cadmium toxicity.

Cadmium (Cd) is an important environmental pollutant and long-term Cd exposure is closely related to autoimmune diseases, cancer, cardiovascular diseases (CVD), and hepatic dysfunction. Zinc (Zn) is an essential metal that plays key roles in protein structure, catalysis, and regulation of their function. Numerous studies have shown that Zn can reduce Cd toxicity; however, the underlying mechanisms have not been extensively explored. Preclinical studies have revealed direct competition for sarcolemmal uptake between these two metals. Multiple sarcolemmal transporters participate in Cd uptake, including Zn transporters, calcium channels, and DMT1 (divalent metal transporter 1). Zn also induces several protective mechanisms, including MT (metallothionein) induction and favorable redox homeostasis. This review summarizes current knowledge related to the role of Zn and metal transporters in reducing Cd toxicity and discusses potential future directions of related research.

Engineered cardiac tissues: a novel in vitro model to investigate the pathophysiology of mouse diabetic cardiomyopathy.

Rodent diabetic models, used to understand the pathophysiology of diabetic cardiomyopathy (DCM), remain several limitations. Engineered cardiac tissues (ECTs) have emerged as robust 3D in vitro models to investigate structure-function relationships as well as cardiac injury and repair. Advanced glycation end-products (AGEs), produced through glycation of proteins or lipids in response to hyperglycemia, are important pathogenic factor for the development of DCM. In the current study, we developed a murine-based ECT model to investigate cardiac injury produced by AGEs. We treated ECTs composed of neonatal murine cardiac cells with AGEs and observed AGE-related functional, cellular, and molecular alterations: (1) AGEs (150 µg/mL) did not cause acute cytotoxicity, which displayed as necrosis detected by medium LDH release or apoptosis detected by cleaved caspase 3 and TUNEL staining, but negatively impacted ECT function on treatment day 9; (2) AGEs treatment significantly increased the markers of fibrosis (TGF-ß, α-SMA, Ctgf, Collagen I-α1, Collagen III-α1, and Fn1) and hypertrophy (Nppa and Myh7); (3) AGEs treatment significantly increased ECT oxidative stress markers (3-NT, 4-HNE, HO-1, CAT, and SOD2) and inflammation response markers (PAI-1, TNF-α, NF-κB, and ICAM-1); and (4) AGE-induced pathogenic responses were all attenuated by pre-application of AGE receptor antagonist FPS-ZM1 (20 µM) or the antioxidant glutathione precursor N-acetylcysteine (5 mM). Therefore, AGEs-treated murine ECTs recapitulate the key features of DCM's functional, cellular and molecular pathogenesis, and may serve as a robust in vitro model to investigate cellular structure-function relationships, signaling pathways relevant to DCM and pharmaceutical intervention strategies.

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms.

Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5-20 µM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50-200 µM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

DFT Investigation of Hydrogen Atom Abstraction from NHC-Boranes by Methyl, Ethyl and Cyanomethyl Radicals-Composition and Correlation Analysis of Kinetic Barriers.

Understanding the hydrogen atom abstraction (HAA) reactions of N-heterocyclic carbene (NHC)-boranes is essential for extending the practical applications of boron chemistry. In this study, density functional theory (DFT) computations were performed for the HAA reactions of a series of NHC-boranes attacked by •CH2CN, Me• and Et• radicals. Using the computed data, we investigated the correlations of the activation and free energy barriers with their components, including the intrinsic barrier, the thermal contribution of the thermodynamic reaction energy to the kinetic barriers, the activation Gibbs free energy correction and the activation zero-point vibrational energy correction. Furthermore, to describe the dependence of the activation and free energy barriers on the thermodynamic reaction energy or reaction Gibbs free energy, we used a three-variable linear model, which was demonstrated to be more precise than the two-variable Evans-Polanyi linear free energy model and more succinct than the three-variable Marcus-theory-based nonlinear HAA model. The present work provides not only a more thorough understanding of the compositions of the barriers to the HAA reactions of NHC-boranes and the HAA reactivities of the substrates but also fresh insights into the suitability of various models for describing the relationships between the kinetic and thermodynamic physical quantities.

Does the Neophyl-like Rearrangement Play a Decisive Role in Intramolecular Cyclization of Iminyl Radicals? A Combined Quantum Chemistry and Numerical Simulation Investigation of the Cyclization Mechanism and Product Distributions of Bicyclic 2-Allyl-2-methyl-2,3-dihydro-1 H-inden-1-iminyl Radical and Several Iminyl Model Compounds.

In this study, we performed a theoretical investigation of the intramolecular cyclization of bicyclic 2-allyl-2-methyl-2,3-dihydro-1 H-inden-1-iminyl radical 1 along with several iminyl model compounds. The results were used to comparatively evaluate the reaction mechanism suggested previously, in which the neophyl-like rearrangement was deemed to play a decisive role. The present computation and numerical simulation identify the experimentally observed endo product in the high-temperature cyclization of 1. The product results from a kinetically controlled endo cyclization-reduction pathway involving an initial reversible 5- exo ring-closure/ring-opening process, not via 5- exo cyclization/neophyl-like rearrangement/ endo-radical reduction pathway as proposed previously. Considering many available theoretical and experimental results, the neophyl-like rearrangement seems to play only a minor role in the intramolecular cyclization of N- and C-centered radicals. The structural effect of cyclized radical intermediates of bicyclic 1 leads to a lower thermodynamic reaction energy of exo cyclization than of endo cyclization, which together with the temperature effect should be responsible for the formation of the dominant endo product in the high-temperature region. Additionally, this investigation provided further insight into the cyclization of 1 and compounds structurally similar to 1; that is, control of endo- or exo-regioselective products is readily available by regulating the reaction temperature.

A Novel Approach of Urinary Monohydroxyphenyl Metabolites Assay in Cancer Screening.

BACKGROUND: A noninvasive, fast, highly sensitive and simple test is needed for cancer screening in addition to the detection of biomarkers in blood. Recently, the patent (CN102565055A) for the Urinary Monohydroxyphenyl Metabolites Assay (UMM-A) was authorized, and the effectiveness of clinical application has yet to be studied further. METHODS: A retrospective study was conducted consisting of 432 cancer patients, 28 benign tumor patients, 117 non-cancerous diseases patients, and 120 healthy donors to analyze the levels of monohydroxyphenyl metabolites in the urine sample. A logistic regression model was used to study the possible confounding factors affecting the diagnostic performance and to test the probability of a case to be positive for UMM-A. RESULTS: Compared with healthy donors, non-cancerous disease, and benign tumor subjects, the positive rate and MM level of UMM-A in cancer patients have significantly increased. After the 246 retreated cancer patients were excluded, and 186 untreated cancer patients were included, with the same specificity to 77.0%, the sensitivity improved from 66.7 to 89.8%, the negative predictive value improved from 58.6 to 91.4%. CONCLUSIONS: The present study has provided important information on the diagnostic characteristics of UMM-A for untreated cancer and its potential application in cancer screening.

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction.

Herein we report a novel palladium-catalyzed reaction that results in phenanthrene derivatives using aryl iodides, ortho-bromobenzoyl chlorides and norbornadiene in one pot. This dramatic transformation undergoes ortho-C-H activation, decarbonylation and subsequent a retro-Diels-Alder process. Pleasantly, this protocol has a wider substrate range, shorter reaction times and higher yields of products than previously reported methods.

Alkenyl Magnesium Compounds: Generation and Synthetic Application.

Alkenyl magnesium compounds have received much attention in synthetic organic chemistry because of their high reactivity. This review summarizes three types of alkenyl magnesium compounds which contain at least one [Mg-C=C] fragment, for example, (1) alkenyl Grignard reagents prepared by halogen-magnesium exchange reaction; (2) alkenyl magnesium carbenoids prepared by halogen-magnesium exchange reaction or sulfoxide-magnesium exchange reaction; (3) magnesacarbocycles containing at least one alkenyl magnesium bond prepared from Zr- or Ti-catalyzed cyclomagnesation or transmetalation, as well as their further reactions and applications.

Selective Transformation of Well-Defined Alkenyllithiums to Alkenylmagnesiums via Transmetalation.

A series of butadienyl organomagnesium complexes, including 1-Li-4-(MgR)-butadienes, 1,4-bis(MgR)-butadienes, and 1-Mg-4-(MgR)-butadiene were synthesized starting with 1,4-dilithio butadienes via the transmetalation reaction between alkenyllithium bond and alkenylmagnesium bond. Single-crystal X-ray structural analysis of these butadienyl organomagnesiates revealed unique bonding modes. Study on their structural transformation demonstrated that 1-Li-4-(MgR)-butadiene is the key intermediate in the reaction process leading to the formation of 1,4-bis(MgR)-butadiene and 1-Mg-4-(MgR)-butadiene.

Oxidative damage of mitochondrial respiratory chain in different organs of a rat model of diet-induced obesity.

PURPOSE: Mitochondrial dysfunction plays an important role in the development of obesity and obesity-associated metabolic diseases. METHODS: In this study, we dynamically observed the characteristics of mitochondrial damage in a rat model of diet-induced obesity (DIO). From the 2nd to the 10th week, animals were killed every 2 weeks and the heart, liver, kidney, and testicular tissues were harvested. Mitochondria were isolated and the activities of respiratory chain complexes I, II, III, and IV as well as the 8-Hydroxy-2-deoxy Guanosine content were determined. Reactive oxygen species and malondialdehyde were measured. RESULTS: Mitochondrial damages were observed in the heart and liver of DIO and DR rats, and the damages occurred later in DR group than that in DIO group. The mitochondrial membrane potential of heart and liver decreased in DIO and DR groups. The activity of the heart mitochondria complexes I, III, and IV (composing NADH oxidative respiratory) was higher in the early stage of DIO and lower in the end of week 10. The higher activity of the liver complexes I, III, and IV was found until the end of week 10 in DIO and DR groups, accompanied with enhanced oxidative stress. Besides, mitochondrial DNA damages were observed in all tissues. CONCLUSION: In DIO rats, the heart mitochondrial dysfunction occurred first and the liver presented the strongest compensatory ability against oxidative stress.

Enhanced field-emission properties of buckled α-borophene by means of Li decoration: a first-principles investigation.

In this study, the structures and field-emission properties of Li-decorated buckled α-borophene (BBP) were investigated by first-principles density functional theory at the PW91 level. Using the computed binding energies, Hirshfeld- and electrostatic potential-derived charges, induced dipole moments, densities of states, and ionization potentials, we evaluated the influence of an applied electric field on the structural stability, work function, and field-emission current of the Li-decorated BBP nanostructures. Furthermore, we also explored the quantitative dependence of the emission current on the electric field, Li concentration, and molecular orbitals. The computed results indicated that increasing the electric field and Li concentration has a considerably positive effect on the field-emission performance of the Li-decorated BBPs. Besides advantages including small work functions and low ionization potentials, most remarkably, the field-emission current can be as high as 48.81 µA in Li4/BBP (supercell with 36 atoms only) under a rather small applied electric field of 0.05 V Å-1, which rivals the highest value of the graphene-BN nanocomposite among all the theoretical nanostructures presented to date. Our results highly support the fact that Li-decorated BBPs can be appealing field-emission cathode materials with an extremely high emission current.

Organocopper(III) Spiro Complexes: Synthesis, Structural Characterization, and Redox Transformation.

Reductive elimination of Cu(III) intermediates is often proposed as a key step in many copper-catalyzed or -mediated formation of C-C or C-heteroatom bonds. However, there still lacks concrete evidence on this key step, mainly because Cu(III) complexes are usually too unstable to be isolated and structurally characterized. In this work, novel organocopper(III) spiro complexes and their analogous organocopper(I) spiro complexes were synthesized and structurally characterized. Single-crystal X-ray structural analysis revealed that the spiro Cu(III) atom adopted a distorted square-planar geometry while its corresponding spiro Cu(I) atom was tetrahedrally coordinated. A redox transformation between these spiro Cu(I) and Cu(III) complexes was experimentally observed by reacting with reductants or oxidants, respectively. As concrete evidence, the organocopper(III) spiro compounds were found to form C-C bonds intramolecularly via reductive elimination.

Response of BAX, Bcl-2 Proteins, and SIRT1/PGC-1α mRNA Expression to 8-Week Treadmill Running in the Aging Rat Skeletal Muscle.

The aim of this study was to analyze the effects of exercise training on Bax and Bcl-2 protein content and sirtuin1 (SIRT1) mRNA expression levels to prevent sarcopenia in aging rats. Eight 18 months old male Sprague-Dawley rats were trained 5 days weekly for 8 weeks on a treadmill, and eight sedentary rats served as controls. Gastrocnemius muscles were dissected 2 days after the last training session. The mRNA content of PGC-1α, caspase-3, NRF1, TFAM, SOD2, and SIRT1 was estimated by RT-PCR with GAPDH used as an internal control. The protein expression of BAX and Bcl-2 was assessed by Western immunoblot. After training, significant (p < 0.05) increases were noted for the gastrocnemius muscle weights, the gastrocnemius mass/body mass ratio, the bcl-2/BAX ratio, the Bcl-2 protein and the SIRT1, PGC-1α, NRF1, TFAM, SOD2 mRNA content in the trained gastrocnemius, relative to the control samples. No difference was found in the BAX protein between control and trained muscles, whereas the caspase-3 mRNA content decreased by 50 %, in the gastrocnemius muscle of trained animals. Exercise training may inhibit age-induced myonuclear apoptosis by stimulating SIRT1/PGC-1α mRNA expression, thereby preventing sarcopenia in aging rat.

Clinical characteristics and outcomes in critical patients with hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination. Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited. The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis. METHODS: A detailed retrospective analysis of clinical records for critical HFRS patients was conducted. The patients enrolled were treated in the centre for infectious diseases, Tangdu Hospital, between January 2008 and August 2012. The clinical characteristics between the survivors and non-survivors were compared by Student's t-test or Chi-square test. The risk clinical factors for prognosis were explored by logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by receiver operating characteristic (ROC) curves. The cumulative proportions surviving at certain intervals in the critical patients were observed by Kaplan-Meier survival analysis. RESULTS: Of the 75 patients enrolled, the cumulative proportion surviving was 70.7% at the second week interval, with a 28-day mortality rate of 36.3%. The non-survivors tended to have higher frequencies of agitation, dyspnea, conjunctival hemorrhage, coma, cardiac failure, acute respiratory distress syndrome (ARDS) and encephalopathy (P < .05). ARDS, conjunctival hemorrhage and coma were risk factors for death in the critical patients with HFRS. The non-survivors were found to have lower serum creatinine (Scr) levels (P < .001) and higher incidences of prolonged prothrombin time (PT) (P = .006), activated partial thromboplastin time (APTT) (P = .003) and elevated white blood cells (WBC) levels (P = .005), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P < .05). CONCLUSION: The high fatality in critical patients with HFRS underscores the importance of clinicians' alertness to the occurrence of potentially fatal complications and changes in biochemical status to ensure that timely and systematically supportive treatment can be initiated when necessary.

Early indicators of severity and construction of a risk model for prognosis based upon laboratory parameters in patients with hemorrhagic fever with renal syndrome.

BACKGROUND: The objective of this study was to explore the role of laboratory parameters as early indicators of severity and as effective predictors of prognosis in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: A total of 356 patients were enrolled in this study and were divided into mild, moderate, severe and critical types according to the clinical classification of HFRS. The levels of 12 routinely tested laboratory parameters during the acute stage among the four types were compared. The predictive values of the laboratory parameters for prognosis were analyzed, and a risk model for prognosis based upon the parameters was constructed. RESULTS: The levels of white blood counts (WBC), platelets (PLT), aspartate aminotransferase (AST), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated significant differences among the four types (p<0.001); WBC, AST, PT and fibrinogen (Fib) were major independent risk factors for death; WBC, AST, PT and Fib used in combination were better for predicting prognosis than single parameters used alone (p<0.001). CONCLUSIONS: Some routinely tested laboratory parameters can be beneficial as early indicators of severity of HFRS. Using a combination of WBC, AST, PT and Fib to predict the outcome in patients with HFRS exhibited acceptable diagnostic capability.