The non-mevalonate pathway requires a delicate balance of intermediates to maximize terpene production.

Terpenes are valuable industrial chemicals whose demands are increasingly being met by bioengineering microbes such as E. coli. Although the bioengineering efforts commonly involve installing the mevalonate (MVA) pathway in E. coli for terpene production, the less studied methylerythritol phosphate (MEP) pathway is a more attractive target due to its higher energy efficiency and theoretical yield, despite its tight regulation. In this study, we integrated an additional copy of the entire MEP pathway into the E. coli genome for stable, marker-free terpene production. The genomically integrated strain produced more monoterpene geraniol than a plasmid-based system. The pathway genes' transcription was modulated using different promoters to produce geraniol as the reporter of the pathway flux. Pathway genes, including dxs, idi, and ispDF, expressed from a medium-strength promoter, led to the highest geraniol production. Quantifying the MEP pathway intermediates revealed that the highest geraniol producers had high levels of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), but moderate levels of the pathway intermediates upstream of these two building blocks. A principal component analysis demonstrated that 1-deoxy-D-xylulose 5-phosphate (DXP), the product of the first enzyme of the pathway, was critical for determining the geraniol titer, whereas MEP, the product of DXP reductoisomerase (Dxr or IspC), was the least essential. This work shows that an intricate balance of the MEP pathway intermediates determines the terpene yield in engineered E. coli. The genetically stable and intermediate-balanced strains created in this study will serve as a chassis for producing various terpenes. KEY POINTS: • Genome-integrated MEP pathway afforded higher strain stability • Genome-integrated MEP pathway produced more terpene than the plasmid-based system • High monoterpene production requires a fine balance of MEP pathway intermediates.

[Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors].

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.

A cytochrome P450 CYP87A4 imparts sterol side-chain cleavage in digoxin biosynthesis.

Digoxin extracted from the foxglove plant is a widely prescribed natural product for treating heart failure. It is listed as an essential medicine by the World Health Organization. However, how the foxglove plant synthesizes digoxin is mostly unknown, especially the cytochrome P450 sterol side chain cleaving enzyme (P450scc), which catalyzes the first and rate-limiting step. Here we identify the long-speculated foxglove P450scc through differential transcriptomic analysis. This enzyme converts cholesterol and campesterol to pregnenolone, suggesting that digoxin biosynthesis starts from both sterols, unlike previously reported. Phylogenetic analysis indicates that this enzyme arises from a duplicated cytochrome P450 CYP87A gene and is distinct from the well-characterized mammalian P450scc. Protein structural analysis reveals two amino acids in the active site critical for the foxglove P450scc's sterol cleavage ability. Identifying the foxglove P450scc is a crucial step toward completely elucidating digoxin biosynthesis and expanding the therapeutic applications of digoxin analogs in future work.

Cardenolide Increase in Foxglove after 2,1,3-Benzothiadiazole Treatment Reveals a Potential Link between Cardenolide and Phytosterol Biosynthesis.

Cardenolides are steroidal metabolites in Digitalis lanata with potent cardioactive effects on animals. In plants, cardenolides are likely involved in various stress responses. However, the molecular mechanism of cardenolide increase during stresses is mostly unknown. Additionally, cardenolides are proposed to arise from cholesterol, but indirect results show that phytosterols may also be substrates for cardenolide biosynthesis. Here, we show that cardenolides increased after methyl jasmonate (MJ), sorbitol, potassium chloride (KCl) and salicylic acid analog [2,1,3-benzothiadiazole (BTH)] treatments. However, the expression of three known genes for cardenolide biosynthesis did not correlate well with these increases. Specifically, the expression of progesterone-5ß-reductases (P5ßR and P5ßR2) did not correlate with the cardenolide increase. The expression of 3ß-hydroxysteroid dehydrogenase (3ßHSD) correlated with changes in cardenolide levels only during the BTH treatment. Mining the D. lanata transcriptome identified genes involved in cholesterol and phytosterol biosynthesis: C24 sterol sidechain reductase 1 (SSR1), C4 sterol methyl oxidase 1, and 3 (SMO1 and SMO3). Surprisingly, the expression of all three genes correlated well with the cardenolide increase after the BTH treatment. Phylogenetic analysis showed that SSR1 is likely involved in both cholesterol and phytosterol biosynthesis. In addition, SMO1 is likely specific to phytosterol biosynthesis, and SMO3 is specific to cholesterol biosynthesis. These results suggest that stress-induced increase of cardenolides in foxglove may correlate with cholesterol and phytosterol biosynthesis. In summary, this work shows that cardenolides are important for stress responses in D. lanata and reveals a potential link between phytosterol and cardenolide biosynthesis.

A well-characterized polycistronic-like gene expression system in yeast.

Efficient expression of multiple genes is critical to yeast metabolic engineering for the bioproduction of bulk and fine chemicals. A yeast polycistronic expression system is of particular interest because one promoter can drive the expression of multiple genes. 2A viral peptides enable the cotranslation of multiple proteins from a single mRNA by ribosomal skipping. However, the wide adaptation of 2A viral peptides for polycistronic-like gene expression in yeast awaits in-depth characterizations. Additionally, a one-step assembly of such a polycistronic-like system is highly desirable. To this end, we have developed a modular cloning (MoClo) compatible 2A peptide-based polycistronic-like system capable of expressing multiple genes from a single promoter in yeast. Characterizing the bi-, tri-, and quad-cistronic expression of fluorescent proteins showed high cleavage efficiencies of three 2A peptides: E2A from equine rhinitis B virus, P2A from porcine teschovirus-1, and O2A from Operophtera brumata cypovirus-18. Applying the polycistronic-like system to produce geraniol, a valuable industrial compound, resulted in comparable or higher titers than using conventional monocistronic constructs. In summary, this highly-characterized polycistronic-like gene expression system is another tool to facilitate multigene expression for metabolic engineering in yeast.

Machine-learning guided elucidation of contribution of individual steps in the mevalonate pathway and construction of a yeast platform strain for terpenoid production.

The production of terpenoids from engineered microbes contributes markedly to the bioeconomy by providing essential medicines, sustainable materials, and renewable fuels. The mevalonate pathway leading to the synthesis of terpenoid precursors has been extensively targeted for engineering. Nevertheless, the importance of individual pathway enzymes to the overall pathway flux and final terpenoid yield is less known, especially enzymes that are thought to be non-rate-limiting. To investigate the individual contribution of the five non-rate-limiting enzymes in the mevalonate pathway, we created a combinatorial library of 243 Saccharomyces cerevisiae strains, each having an extra copy of the mevalonate pathway integrated into the genome and expressing the non-rate-limiting enzymes from a unique combination of promoters. High-throughput screening combined with machine learning algorithms revealed that the mevalonate kinase, Erg12p, stands out as the critical enzyme that influences product titer. ERG12 is ideally expressed from a medium-strength promoter which is the 'sweet spot' resulting in high product yield. Additionally, a platform strain was created by targeting the mevalonate pathway to both the cytosol and peroxisomes. The dual localization synergistically increased terpenoid production and implied that some mevalonate pathway intermediates, such as mevalonate, isopentyl pyrophosphate (IPP), and dimethylallyl pyrophosphate (DMAPP), are diffusible across peroxisome membranes. The platform strain resulted in 94-fold, 60-fold, and 35-fold improved titer of monoterpene geraniol, sesquiterpene α-humulene, and triterpene squalene, respectively. The terpenoid platform strain will serve as a chassis for producing any terpenoids and terpene derivatives.

Resolving the Rules of Robustness and Resilience in Biology Across Scales.

Why do some biological systems and communities persist while others fail? Robustness, a system's stability, and resilience, the ability to return to a stable state, are key concepts that span multiple disciplines within and outside the biological sciences. Discovering and applying common rules that govern the robustness and resilience of biological systems is a critical step toward creating solutions for species survival in the face of climate change, as well as the for the ever-increasing need for food, health, and energy for human populations. We propose that network theory provides a framework for universal scalable mathematical models to describe robustness and resilience and the relationship between them, and hypothesize that resilience at lower organization levels contribute to robust systems. Insightful models of biological systems can be generated by quantifying the mechanisms of redundancy, diversity, and connectivity of networks, from biochemical processes to ecosystems. These models provide pathways towards understanding how evolvability can both contribute to and result from robustness and resilience under dynamic conditions. We now have an abundance of data from model and non-model systems and the technological and computational advances for studying complex systems. Several conceptual and policy advances will allow the research community to elucidate the rules of robustness and resilience. Conceptually, a common language and data structure that can be applied across levels of biological organization needs to be developed. Policy advances such as cross-disciplinary funding mechanisms, access to affordable computational capacity, and the integration of network theory and computer science within the standard biological science curriculum will provide the needed research environments. This new understanding of biological systems will allow us to derive ever more useful forecasts of biological behaviors and revolutionize the engineering of biological systems that can survive changing environments or disease, navigate the deepest oceans, or sustain life throughout the solar system.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

A dual cellular-heterogeneous catalyst strategy for the production of olefins from glucose.

Living systems provide a promising approach to chemical synthesis, having been optimized by evolution to convert renewable carbon sources, such as glucose, into an enormous range of small molecules. However, a large number of synthetic structures can still be difficult to obtain solely from cells, such as unsubstituted hydrocarbons. In this work, we demonstrate the use of a dual cellular-heterogeneous catalytic strategy to produce olefins from glucose using a selective hydrolase to generate an activated intermediate that is readily deoxygenated. Using a new family of iterative thiolase enzymes, we genetically engineered a microbial strain that produces 4.3 ± 0.4 g l-1 of fatty acid from glucose with 86% captured as 3-hydroxyoctanoic and 3-hydroxydecanoic acids. This 3-hydroxy substituent serves as a leaving group that enables heterogeneous tandem decarboxylation-dehydration routes to olefinic products on Lewis acidic catalysts without the additional redox input required for enzymatic or chemical deoxygenation of simple fatty acids.

[Luteolin has a significant protective effect against cadmium-induced injury in lung epithelial Beas-2B cells].

OBJECTIVE: To investigate the protective effect of luteolin against cadmium (Cd)-induced injury in human lung epithelial Beas-2B cells. OBJECTIVE: Beas-2B cells were treated with different concentrations of luteolin (0-160 µmol/L) or Cd (0-40 µmol/L) for 24 h, and the cell viability was examined using MTT assay. After treatment with luteolin (0.25, 0.5 and 0.75 µmol/L) with or without Cd (5 µmol/L) for 24 h, the cells were examined for viability, lactate dehydrogenase (LDH) activity and morphological changes of the cell nuclei using Hoechst fluorescent staining. The levels of ROS, SOD, GSH and MDA in the treated cells were detected, and the expression levels of Akt, p-Akt and nuclear factor E2-related factor 2 (Nrf2) proteins were determined using Western blotting. OBJECTIVE: Luteolin within the concentration range of 0-80 µmol/L did not significantly affect the survival rate of Beas-2B cells (P>0.05), but Cd at 5 µmol/L significantly decreased the cell viability (P < 0.05) with an IC50 of 24.6 µmol/L. In Cd-treated cells, treatment with luteolin significantly mitigated the decrease of cell viability, reduced LDH release and cell apoptosis, enhanced SOD activity and GSH content, and inhibited the production of MDA and ROS (all P < 0.05). Luteolin also significantly up-regulated the expression levels of p-Akt and Nrf2 protein in Cd-treated Beas-2B cells (P < 0.05). OBJECTIVE: Luteolin has a significant protective effect against Cd-induced injury in Beas-2B cells, and the effects are probably mediated, at least in part, by promoting the activation of Akt and Nrf2.

Rapid Assembly of Multi-Gene Constructs using Modular Golden Gate Cloning.

The Golden Gate cloning method enables the rapid assembly of multiple genes in any user-defined arrangement. It utilizes type IIS restriction enzymes that cut outside of their recognition sites and create a short overhang. This modular cloning (MoClo) system uses a hierarchical workflow in which different DNA parts, such as promoters, coding sequences (CDS), and terminators, are first cloned into an entry vector. Multiple entry vectors then assemble into transcription units. Several transcription units then connect into a multi-gene plasmid. The Golden Gate cloning strategy is of tremendous advantage because it allows scar-less, directional, and modular assembly in a one-pot reaction. The hierarchical workflow typically enables the facile cloning of a large variety of multi-gene constructs with no need for sequencing beyond entry vectors. The use of fluorescent protein dropouts enables easy visual screening. This work provides a detailed, step-by-step protocol for assembling multi-gene plasmids using the yeast modular cloning (MoClo) kit. We show optimal and suboptimal results of multi-gene plasmid assembly and provide a guide for screening for colonies. This cloning strategy is highly applicable for yeast metabolic engineering and other situations in which multi-gene plasmid cloning is required.

Genome-wide Analyses Identify a Novel Risk Locus for Nonsyndromic Cleft Palate.

The 3 major subphenotypes observed in patients with nonsyndromic orofacial clefts (NSOFCs) are nonsyndromic cleft lip only (NSCLO), nonsyndromic cleft lip with palate (NSCLP), and nonsyndromic cleft palate only (NSCPO). However, the genetic architecture underlying NSCPO is largely unknown. Here we performed a 2-stage genome-wide association study (GWAS) on NSCPO and replication analyses of selected variants in other NSOFCs from the Chinese Han population. We identified a novel locus (15q24.3) and a known locus (1q32.2) where variants in or near the gene reached genome-wide significance (2.80 × 10-13 < P < 1.72 × 10-08) in a test for association with NSCPO in a case-control design. Although a variant from 15q24.3 was found to be significantly associated with both NSCPO and NSCLP, the direction of estimated effects on risk were opposite. Our functional annotation of the risk alleles within 15q24.3 coupled with previously established roles of the candidate genes within identified risk loci in periderm development, embryonic patterning, and/or regulation of cellular processes supports their involvement in palate development and the pathogenesis of cleft palate. Our study advances the understanding of the genetic basis of NSOFCs and provides novel insights into the pathogenesis of NSCPO.

High-resolution tandem mass spectrometry dataset reveals fragmentation patterns of cardiac glycosides in leaves of the foxglove plants.

Cardiac glycosides, steroid derivatives extracted from the foxglove plants, have been used for the treatment of heart failure since the 18th century. A method based on liquid chromatography coupled with high-resolution tandem mass spectrometry (LC/MS2) has been developed to characterize and quantify cardiac glycosides in fresh-leaf extracts of the foxglove (Digitalis sp.) plants [1]. In this report, the fragmentation spectra of additional authentic standards of cardiac glycoside (digitoxigenin, digoxigenin, ß-acetyldigoxin) and cardenolides identified in the leaves of Digitalis lanata (D. lanata) and Digitalis purpurea (D. purpurea) were provided with high resolution. The exact mass of signature peaks for the aglycones and the sugar units of cardenolides were measured. This dataset is valuable to researchers interested in characterizing cardenolides in plants, or quantifying cardenolides in drug tablets, or studying cardenolide toxicities in animals. The fragmentation patterns of authentic cardenolide standards provided in these data can be used to validate relevant cardenolides in various biological samples and to infer chemical structures of unknown cardiac glycosides.

Profiling and structural analysis of cardenolides in two species of Digitalis using liquid chromatography coupled with high-resolution mass spectrometry.

Plants of the Digitalis genus contain a cocktail of cardenolides commonly prescribed to treat heart failure. Cardenolides in Digitalis extracts have been conventionally quantified by high-performance liquid chromatography yet the lack of structural information compounded with possible co-eluents renders this method insufficient for analyzing cardenolides in plants. The goal of this work is to structurally characterize cardiac glycosides in fresh-leaf extracts using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) that provides measured accurate mass. Fragmentation of cardenolides is featured by sequential loss of sugar units while the steroid aglycone moieties undergo stepwise elimination of hydroxyl groups, which distinguishes different aglycones. Using a reverse-phase LC column, the sequence of elution follows: diginatigenin→digoxigenin→gitoxigenin→gitaloxigenin→digitoxigenin for cardenolides with the same sugar units but different aglycones. A linear range of 0.8-500 ng ml-1 has been achieved for digoxigenin, ß-acetyldigoxin, and digitoxigenin with limits of detection ranging from 0.09 to 0.45 ngml-1. A total of seventeen cardenolides have been detected with lanatoside A, C, and E as major cardenolides in Digitalis lanata while seven have been found in Digitalis purpurea including purpurea glycoside A, B, and E. Surprisingly, glucodigifucoside in D. lanata and verodoxin and digitoxigenin fucoside in D. purpurea have also been found as major cardenolides. As the first MS/MS-based method developed for analyzing cardenolides in plant extracts, this method serves as a foundation for complete identification and accurate quantification of cardiac glycosides, a necessary step towards understanding the biosynthesis of cardenolide in plants.

LINC00963 predicts poor prognosis and promotes esophageal cancer cells invasion via targeting miR-214-5p/RAB14 axis.

OBJECTIVE: To explore the roles and underlying mechanism of LINC00963 in esophageal squamous cell carcinoma (ESCC) progression. PATIENTS AND METHODS: Quantitative Real Time-PCR (qRT-PCR) was used to detect LINC00963 expression in ESCC tissues. EdU, colony formation, and transwell invasion assays were used to detect the proliferation and metastasis ability of ESCC, respectively. The correlation between LINC00963 and miR-214-5p in ESCC was confirmed by a Luciferase reporter and RIP assays. RESULTS: LINC00963 expression was significantly increased in ESCC tissues and correlated with advanced TNM stage, metastasis, and poor prognosis. The knockdown of LINC00963 expression reduced ESCC cells proliferation, invasion in vitro, and reduced tumor growth in vivo. In mechanism, LINC00963 served as a sponge for miR-214-5p in ESCC progression. In addition, miR-214-5p could bind to RAB14 and regulate its expression. CONCLUSIONS: LINC00963 might promote ESCC cells proliferation and invasion via regulating the miR-214-5p/RAB14 axis and it might serve as a therapeutic target for ESCC treatment.

Capacity of a body shape index and body roundness index to identify diabetes mellitus in Han Chinese people in Northeast China: a cross-sectional study.

AIM: To assess the capacity of a body shape index and body roundness index to identify people with diabetes mellitus and those with prediabetes, and to determine whether a body shape index and/or body roundness index is superior to the traditional overall adiposity index, BMI, in Han Chinese people in Northeast China. METHODS: A total of 15 078 participants were enrolled from Jilin province in 2012 using a multi-stage stratified random cluster sampling method. Demographic data were collected, and anthropometric indices and biochemical indices were measured. Receiver-operating characteristic curves were used to compare the validity of each anthropometric index, and the area under the receiver-operating characteristic curve was calculated for each anthropometric index. RESULTS: Body roundness index had the highest areas under the receiver-operating curve for prediabetes, diagnosed diabetes and undiagnosed diabetes in both men and women (all P<0.01). The optimum threshold values for body roundness index for prediabetes, undiagnosed diabetes and diagnosed diabetes, respectively, were 2.8, 3.7 and 3.3 in men, and 3.4, 3.8 and 3.6 in women. The cumulative proportions of prediabetes, undiagnosed diabetes and diagnosed diabetes identified by the optimum threshold values of body roundness index were 79.2%, 67.5% and 77.0% (82.3%, 62.5% and 75.3% in men; 74.6%, 74.9% and 78.3% in women), respectively. CONCLUSIONS: BMI, a body shape index and body roundness index may identify the presence of diabetes. Among the three anthropometric indices, BMI had the weakest association with diabetes. Body roundness index is an alternative index for assessing diabetes in Han Chinese people in Northeast China.

Recent advances in management of tuberculosis in infants.

The global tuberculosis (TB) incidence estimated by WHO is found to be 8.6 million people. Moreover, the highest TB burden worldwide is found in Asian and African countries. The disease is more prevalent in infants due to their immature immune systems. Despite this, the available diagnostic tools pose a challenge due to paucibacillary nature of the disease and difficulty in obtaining specimens. The present review article discusses the important and upcoming advancements in the management of above pathological state. The article will enlighten the new vaccinations for TB in the pipeline. Moreover, new upcoming approaches involving system biology and gene expression profiling for efficient supervision of the disease will also be highlighted.

[A Fisher discriminant model to predict the outcome of postoperative blood pressure in primary aldosteronism].

Objective: To establish a Fisher discriminant model in order to predict the outcome of postoperative blood pressure for primary aldosteronism (PA). Methods: A total of 83 cases from the First Affiliated Hospital of Chongqing Medical University were enrolled and divided into two groups: cure group and not cure group according to postoperative blood pressure. Fisher stepwise discriminant analysis was used to establish a discriminant model, and compared with aldosteronoma resolution score (ARS) and nomogram model by receiver operating characteristic curve. Results: Hypertension was cured in 52 cases, and 31 cases remained uncured. Patients in uncured group were older, and had bigger body mass index (BMI), longer duration of hypertension, higher serum triglyceride (TG), more types of antihypertensive drug, higher incidence of diabetes, smoking and alcohol intake, less typical nodules on computed tomography imaging, lower estimated glomerular filtration rate (eGFR) and high density lipoprotein cholesterol. The discriminant model based on BMI, types of antihypertensive drugs, typical nodules on CT, eGFR and TG was established and the cut-off value was 0.195 9, with a sensitivity of 86.5% and a specificity of 83.9%. The area under the curve was 0.857 (95% CI: 0.764-0.951), which was higher than that of ARS (0.733, 95% CI: 0.619-0.847) and the nomogram model (0.735, 95% CI: 0.619-0.851). Conclusion: The Fisher discriminant model had a high value to predict the outcome of postoperative blood pressure in PA.

Magnesium sulfate micro air pump suction for bronchiolitis treatment in infants under two years old.

OBJECTIVE: To investigate the efficiency, clinical effects and nursing methods related to the use of magnesium sulfate micro air pump suction for treating infants under two years old suffering from bronchiolitis. PATIENTS AND METHODS: From January 2014 to September 2014, ninety-six infants with capillary bronchitis were enrolled. Patients were randomly divided into two groups: experimental group (n=49) and control group (n=47). All patients went through conventional anti-inflammatory therapy. Based on this, infants in the control group were additionally treated with intravenous drip of magnesium sulfate while patients in the experimental group were treated with magnesium sulfate micro air pump suction. We recorded all changes in blood gas and clinical scores, the residence time of symptoms and signs of bronchiolitis, and hospitalization time. Results obtained on clinical effects and adverse reactions were compared and analyzed. RESULTS: The Variations of PaO2, PaCO2, SaO2 before treatment in both groups did not show any statistically significant differences (p>0.05); while after treatment analyses demonstrated that in both groups we had an increase in PaO2 and SaO2 and a decrease in PaCO2. The increase in PaO2 and SaO2 values were more pronounced while the decrease observed in PaCO2 was more significant in our experimental group. The total effective rate was significantly higher while the total adverse reaction rate, the resolution time of clinical symptoms and hospitalization time were significantly lower in our experimental group. CONCLUSIONS: Magnesium sulfate micro air pump suction was safe and effective in treating with bronchiolitis of infants below 2 years old, and its adverse reaction rate was low, nursing procedure was simple, and nursing difficulty level was low.

Heat shock protein 70 polymorphisms in Chinese patients with Graves' disease.

Graves' disease (GD) is a common autoimmune disease mainly affecting the thyroid. However, the correlation between the development of GD and HSP70 alleles has not been reported in the Chinese population. Therefore, the aim of this study was to investigate the association between HSP70 polymorphisms and GD in the Chinese population. A total of 153 patients with GD treated at the Yan'an Affiliated Hospital of Kunming Medical University between October 2010 and August 2013 were enrolled in this study; one hundred and twenty healthy volunteers were included in the control group. HSP70 polymorphisms at positions HSP70-1 +190, HSP70-2 +1267, and HSP70-hom +2437 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The distribution of the HSP70-2 +1267 GG genotype allele frequencies among GD and control subjects differed significantly (χ(2) = 20.40, P < 0.001; χ(2) = 18.18, P < 0.001). The G allele of HSP70-2 +1267 (Odds ratio = 0.455, 95% confidence interval: 0.315-0.655) conferred a higher risk of developing GD than the A allele. We observed no significant differences in the allelic frequencies of HSP70-1 +190 and HSP70-hom +2437. Therefore, the HSP70-2 +1267 GG genotype and the G allele may increase the risk of GD in Chinese subjects. The results of this study may be useful in identifying patients with increased risk of GD, and offer useful reference data for targeted gene therapy of GD in the future.