Simplifying Genotyping of Mutants from Genome Editing with a Parallel qPCR-Based iGenotype Index.

Targeted genome editing is a powerful tool in reverse genetic studies of gene function in many aspects of biological and pathological processes. The CRISPR/Cas system or engineered endonucleases such as ZFNs and TALENs are the most widely used genome editing tools that are introduced into cells or fertilized eggs to generate double-strand DNA breaks within the targeted region, triggering cellular DNA repair through either homologous recombination or non-homologous end joining (NHEJ). DNA repair through the NHEJ mechanism is usually error-prone, leading to point mutations or indels (insertions and deletions) within the targeted region. Some of the mutations in embryos are germline transmissible, thus providing an effective way to generate model organisms with targeted gene mutations. However, point mutations and short indels are difficult to be effectively genotyped, often requiring time-consuming and costly DNA sequencing to obtain reliable results. Here, we developed a parallel qPCR assay in combination with an iGenotype index to allow simple and reliable genotyping. The genotype-associated iGenotype indexes converged to three simple genotype-specific constant values (1, 0, -1) regardless of allele-specific primers used in the parallel qPCR assays or gene mutations at wide ranges of PCR template concentrations, thus resulting in clear genotype-specific cutoffs, established through statistical analysis, for genotype identification. While we established such a genotyping assay in the Xenopus tropicalis model, the approach should be applicable to genotyping of any organism or cells and can be potentially used for large-scale, automated genotyping.

ASSESS-IE: a Novel Risk Score for Patients with Infective Endocarditis.

Mortality in patients with infective endocarditis (IE) remains high. The existing risk scores are relatively complex with limited clinical application. This study was conducted to establish a new risk model to predict in-hospital and 6-month mortality in IE patients. A total of 1549 adult patients with definite IE admitted to Guangdong Provincial People's Hospital (n=1354) or Xiamen Cardiovascular Hospital (n=195) were included. The derivation cohort consisted of 1141 patients. The score was developed using the multivariate stepwise logistic regression analysis for in-hospital death. Bootstrap analysis was used for validation. Discrimination and calibration were evaluated by the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test. Six risk factors were used as score parameters (1 point for each): aortic valve affected, previous valve replacement surgery, severe heart failure, elevated serum direct bilirubin, moderate-severe anemia and acute stage. The predictive value and calibration of the ASSESS-IE score for in-hospital death were excellent in the derivation (area under the curve [AUC]=0.781, p<0.001; Hosmer-Lemeshow p=0.948) and validation (AUC=0.779, p<0.001; Hosmer-Lemeshow p=0.520) cohorts. The score remained excellent in bootstrap validation (AUC=0.783). The discriminatory ability of the ASSESS-IE score for in-hospital (AUC: 0.781 vs. 0.799, p=0.398) and 6-month mortality (AUC: 0.778 vs. 0.814, p=0.040) were similar with that of Park's score which comprised 14 variables. The ASSESS-IE risk score is a new and robust risk-stratified tool for patients with IE, which might further facilitate clinical decision-making.

Essential and subtype-dependent function of thyroid hormone receptors during Xenopus metamorphosis.

Thyroid hormone (T3) plays critical roles in organ metabolism and development in vertebrates. Anuran metamorphosis is perhaps the most dramatic and best studied developmental process controlled by T3. Many changes in different organs/tissues during anuran metamorphosis resemble the maturation/remodeling of the corresponding organs/tissues during mammalian postembryonic development. The plasma T3 level peaks during both anuran metamorphosis and mammalian postembryonic development. T3 exerts its developmental function through transcriptional regulation via T3 receptors (TRs). Studies on the metamorphosis of two highly related anurans, pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, have led to a dual function model for TRs during development. This has been supported by strong molecular and genetic evidence. Here we review some of the evidence with a focus on more recent gene knockout studies in Xenopus tropicalis. These studies have not only supported the model but also revealed novel and TR subtype-specific roles during Xenopus development, particularly a critical role of TRα in controlling developmental timing and rate.

Liver development during Xenopus tropicalis metamorphosis is controlled by T3-activation of WNT signaling.

Thyroid hormone (T3) regulates vertebrate organ development, growth, and metabolism through the T3 receptor (TR). Due to maternal influence in mammals, it has been difficult to study if and how T3 regulates liver development. Liver remodeling during anuran metamorphosis resembles liver maturation in mammals and is controlled by T3. We generated Xenopus tropicalis animals with both TRα and TRß genes knocked out and found that TR double knockout liver had developmental defects such as reduced cell proliferation and failure to undergo hepatocyte hypertrophy or activate urea cycle gene expression. RNA-seq analysis showed that T3 activated canonical Wnt pathway in the liver. Particularly, Wnt11 was activated in both fibroblasts and hepatic cells, and in turn, likely promoted the proliferation and maturation of hepatocytes. Our study offers new insights into not only how T3 regulates liver development but also on potential means to improve liver regeneration.

Thyroid hormone receptor knockout prevents the loss of Xenopus tail regeneration capacity at metamorphic climax.

BACKGROUND: Animal regeneration is the natural process of replacing or restoring damaged or missing cells, tissues, organs, and even entire body to full function. Studies in mammals have revealed that many organs lose regenerative ability soon after birth when thyroid hormone (T3) level is high. This suggests that T3 play an important role in organ regeneration. Intriguingly, plasma T3 level peaks during amphibian metamorphosis, which is very similar to postembryonic development in humans. In addition, many organs, such as heart and tail, also lose their regenerative ability during metamorphosis. These make frogs as a good model to address how the organs gradually lose their regenerative ability during development and what roles T3 may play in this. Early tail regeneration studies have been done mainly in the tetraploid Xenopus laevis (X. laevis), which is difficult for gene knockout studies. Here we use the highly related but diploid anuran X. tropicalis to investigate the role of T3 signaling in tail regeneration with gene knockout approaches. RESULTS: We discovered that X. tropicalis tadpoles could regenerate their tail from premetamorphic stages up to the climax stage 59 then lose regenerative capacity as tail resorption begins, just like what observed for X. laevis. To test the hypothesis that T3-induced metamorphic program inhibits tail regeneration, we used TR double knockout (TRDKO) tadpoles lacking both TRα and TRß, the only two receptor genes in vertebrates, for tail regeneration studies. Our results showed that TRs were not necessary for tail regeneration at all stages. However, unlike wild type tadpoles, TRDKO tadpoles retained regenerative capacity at the climax stages 60/61, likely in part by increasing apoptosis at the early regenerative period and enhancing subsequent cell proliferation. In addition, TRDKO animals had higher levels of amputation-induced expression of many genes implicated to be important for tail regeneration, compared to the non-regenerative wild type tadpoles at stage 61. Finally, the high level of apoptosis in the remaining uncut portion of the tail as wild type tadpoles undergo tail resorption after stage 61 appeared to also contribute to the loss of regenerative ability. CONCLUSIONS: Our findings for the first time revealed an evolutionary conservation in the loss of tail regeneration capacity at metamorphic climax between X. laevis and X. tropicalis. Our studies with molecular and genetic approaches demonstrated that TR-mediated, T3-induced gene regulation program is responsible not only for tail resorption but also for the loss of tail regeneration capacity. Further studies by using the model should uncover how T3 modulates the regenerative outcome and offer potential new avenues for regenerative medicines toward human patients.

Changes of cardiac output and velocity time integral in blood return at the end of renal replacement therapy predict fluid responsiveness in critically Ill patients with acute circulatory failure.

OBJECTIVES: To observe if blood return, also defined as the blood infusion test (BIT) could predict fluid responsiveness in critically ill patients with acute circulatory failure and renal replacement therapy (RRT). METHODS: This was a single-center, prospective, diagnostic accuracy study. Before BIT, the passive leg raise test (PLRT) was performed to record the change of cardiac output (ΔCO) by pulse contour analysis, and ΔCO > = 10% was defined as the fluid responder. Meanwhile, the change in velocity time integral (ΔVTI) was recorded by ultrasound. Later, the ΔCO and ΔVTI during BIT were recorded 5-10 min after PLRT. The receiver-operating characteristic curves of ΔCO and ΔVTI of BIT were performed in predicting the fluid responder defined by PLRT. RESULTS: A total of 43 patients with acute circulatory failure undergoing RRT were enrolled in the present study, and 25 patients (58.1%) were recognized as responders during PLRT. According to the receiver-operating characteristic curves, the cutoff value of ΔCO was 10% and ΔVTI was 9% during BIT with the area under curve of 0.96 and 0.94, respectively. CONCLUSIONS: BIT in RRT could identify fluid responsiveness in critically ill patients with shock. TRIAL REGISTRATION: ChiCTR-DDD-17010534. Registered on 30/01/2017 (retrospective registration).

Comparative Analysis of Transcriptome Profiles Reveals Distinct and Organ-Dependent Genomic and Nongenomic Actions of Thyroid Hormone in Xenopus tropicalis Tadpoles.

Background: Thyroid hormone (triiodothyronine [T3]) is essential for development and organ metabolism in all vertebrates. T3 has both genomic and nongenomic effects on target cells. While much has been learnt on its genomic effects via T3 receptors (TRs) in vertebrate development, mostly through TR-knockout and TR-knockin studies, little is known about the effects of T3 on gene expression in animals in the absence of TR. We have been studying Xenopus metamorphosis as a model for mammalian postembryonic development, a period around birth when plasma T3 level peaks and many organs/tissues mature into their adult forms. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals. This offers an opportunity to compare the effects of T3 on global gene expression in tadpole tissues in the presence or absence of TR. Methods: We analyzed the effects of T3 on gene expression in tadpole tail and intestine by using RNA-seq analysis on wild-type and TRDKO tadpoles with or without T3 treatment. Results: We observed that removing TRs reduced the number of genes regulated by T3 in both organs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that T3 affected distinct biological processes and pathways in wild-type and TRDKO tadpoles. Many GO terms and KEGG pathways that were enriched among genes regulated in wild-type tissues are likely involved in mediating the effects of T3 on metamorphosis, for example, those related to development, stem cells, apoptosis, and cell cycle/cell proliferation. However, such GO terms and pathways were not enriched among T3-regulated genes in TRDKO tadpoles. Instead, in TRDKO tadpoles, GO terms and pathways related to "metabolism" and "immune response" were highly enriched among T3-regulated genes. We further observed strong divergence in the TR-independent nongenomic effects of T3 in the intestine and tail. Conclusions: Our data suggest that T3 has distinct and organ-dependent effects on gene expression in developing tadpoles. The TR-mediated effects are consistent with the metamorphic changes, in agreement with the fact that TR is necessary and sufficient to mediate the effects of T3 on metamorphosis. T3 appears to have a major effect on metabolism and immune response via TR-independent nongenomic processes.

Pcv-aCO2 and procalcitonin levels for the early diagnosis of bloodstream infections caused by gram-negative bacteria.

BACKGROUND: The central venous-to-arterial carbon dioxide difference (Pcv-aCO2) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO2 in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO2 and procalcitonin (PCT) in the early stages of GN bacteria BSI. METHODS: Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO2 and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients. RESULTS: A total of 132 patients with BSI were enrolled. The Pcv-aCO2 (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO2 was 0.823 (95% confidence interval (CI): 0.746-0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745-0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively. CONCLUSIONS: Pcv-aCO2 and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.

Low-Density Lipoprotein Cholesterol and Mortality Risk in Elderly Patients Undergoing Valve Replacement Surgery: A Propensity Score Matching Analysis.

Background: The prognostic value of low-density lipoprotein cholesterol (LDL-C) in elderly patients is controversial. This study aimed to elucidate the relationship between the preoperative LDL-C and adverse outcomes in elderly patients undergoing valve replacement surgery (VRS). Methods: A total of 2,552 aged patients (age ≥ 60 years) undergoing VRS were retrospectively recruited and divided into two groups according to LDL-C level on admission: low LDL-C (<70 mg/dL, n = 205) and high LDL-C groups (≥ 70 mg/dL, n = 2,347). The association between the preoperative LDL-C with in-hospital and one-year mortality was evaluated by propensity score matching analysis and multivariate analysis. Results: The mean age was 65 ± 4 years and 1,263 (49.5%) were men. Patients in the low LDL-C group were significantly older (65.9 ± 4.6 vs. 64.9 ± 4.1, p = 0.002), with more male (65.4 vs. 48.1%, p < 0.001), higher alanine transaminase (ALT) (21 vs. 19, p = 0.001), lower serum albumin (35.3 ± 4.6 vs. 37.1 ± 4.1, p < 0.001), higher serum creatinine (92.2 ± 38.2 vs.84.6 ± 26.1, p = 0.006), lower lymphocyte count (1.7 ± 0.7 vs. 1.9 ± 0.6, p < 0.001), lower hemoglobin (121.9 ± 22.3 vs. 130.2 ± 16.5, p < 0.001), lower platelet count (171.3 ± 64.3 vs. 187.7 ± 58.7, p < 0.001), lower prognostic nutrition index (44 ± 6.2 vs. 46.7 ± 5.8, p < 0.001), and more severe tricuspid regurgitation (33.7 vs. 25.1%, p = 0.008). The rates of in-hospital death (11.2 vs. 3.7%, p < 0.001) and major adverse clinical events (17.6 vs. 9.6%, p < 0.001) were significantly higher in the low LDL-C group. The cumulative one-year death rate was significantly higher in the low LDL-C group (Log-Rank = 16.6, p < 0.001). After matching analysis and multivariate analysis, no association between LDL-C level and adverse outcomes was detected (all p > 0.05). Conclusion: Our study did not support the negative relationship between LDL-C level and mortality risk in elderly patients undergoing VRS.

Hypernatremia in brain-dead patients.

OBJECTIVES: Hypernatremia often occurs in patients with brain death. This study summarizes its characteristics. METHODS: We recorded 57 patient's highest blood sodium value, as well as daily NT-proBNP, blood creatinine, and urine output. Further, we analyzed the time of the first rise in blood sodium, and the relationship between NT-proBNP, serum creatinine, urine output, and serum sodium. RESULTS: There was no hyponatremia in these patients, and only seven of the 53 patients registered blood sodium between 137 and 150 mmol/L. We found that blood sodium started to rise at 36.0 (28.5-52.3) h, reaching the highest value in 79.0 (54.0-126.0) h. Urine volume and creatinine have no correlation with serum sodium level, while NT-proBNP has a significant correlation with serum sodium level. CONCLUSION: It is necessary to conduct volume assessments and urine electrolyte testing on patients with brain death. BNP has a protective effect on water and electrolytes to prevent hypernatremia.

Red blood cell distribution width: A severity indicator in patients with COVID-19.

Red blood cell distribution width (RDW) was frequently assessed in COVID-19 infection and reported to be associated with adverse outcomes. However, there was no consensus regarding the optimal cutoff value for RDW. Records of 98 patients with COVID-19 from the First People's Hospital of Jingzhou were reviewed. They were divided into two groups according to the cutoff value for RDW on admission by receiver operator characteristic curve analysis: ≤11.5% (n = 50) and >11.5% (n = 48). The association of RDW with the severity and outcomes of COVID-19 was analyzed. The receiver operating characteristic curve indicated that the RDW was a good discrimination factor for identifying COVID-19 severity (area under the curve = 0.728, 95% CI: 0.626-0.830, p < 0.001). Patients with RDW > 11.5% more frequently suffered from critical COVID-19 than those with RDW ≤ 11.5% (62.5% vs. 26.0%, p < 0.001). Multivariate logistic regression analysis showed RDW to be an independent predictor for critical illness due to COVID-19 (OR = 2.40, 95% CI: 1.27-4.55, p = 0.007). A similar result was obtained when we included RDW > 11.5% into another model instead of RDW as a continuous variable (OR = 5.41, 95% CI: 1.53-19.10, p = 0.009). RDW, as an inexpensive and routinely measured parameter, showed promise as a predictor for critical illness in patients with COVID-19 infection. RDW > 11.5% could be the optimal cutoff to discriminate critical COVID-19 infection.

The effect of preoperative statin treatment on acute kidney injury in elderly patients undergoing valve replacement surgery.

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.

Transcriptome profiling reveals gene regulation programs underlying tail development in the Ornamented Pygmy frog Microhyla fissipes.

Introduction: Tadpole tail develops from the tailbud, an apparently homogenous mass of cells at the posterior of the embryo. While much progress has been made in understanding the origin and the induction of the tailbud, the subsequent outgrowth and differentiation have received much less attention, particularly with regard to global gene expression changes. Methods: By using RNA-seq with SMRT and further analyses, we report the transcriptome profiles at four key stages of tail development, from a small tailbud to the onset of feeding (S18, S19, S21 and S28) in Microhyla fissipes, an anuran with a number of advantages for developmental and genetic studies. Results: We obtained 48,826 transcripts and discovered 8807 differentially expressed transcripts (DETs, q < 0.05) among these four developmental stages. We functionally classified these DETs by using GO and KEGG analyses and revealed 110 significantly enriched GO categories and 6 highly enriched KEGG pathways (Protein digestion and absorption; ECM-receptor interaction; Pyruvate metabolism; Fatty acid degradation; Valine, leucine and isoleucine degradation; and Glyoxylate and dicarboxylate metabolism) that are likely critically involved in developmental changes in the tail. In addition, analyses of DETs between any two individual stages demonstrated the involvement of distinct biological pathways/GO terms at different stages of tail development. Furthermore, the most dramatic changes in gene expression profile are those between S28 and any of the other three stages. The upregulated DETs at S28 are highly enriched in "myosin complex" and "potassium channel activity", which are important for muscle contraction, a critical function of the tail that the animal needs by the end of embryogenesis. Additionally, many DETs and enriched pathways discovered here during tail development, such as HDAC1, Hes1 and Hippo signaling pathway, have also been reported to be vital for the tissue/organ regeneration, suggesting conserved functions between development and regeneration. Conclusion: The present staudy provides a golbal overview of gene expression patterns and new insights into the mechanism involved in anuran tail development and regeneration.

Diagnosing scrub typhus without eschar: a case report using metagenomic next-generation sequencing (mNGS).

Scrub typhus is a disease caused by the bacteria, Orientia tsutsugamushi, which is spread to people through the bites of infected larval mites. Symptoms include eschar at the place of infection, as well as many flu-like symptoms, e.g., fever, headache, chills and skin rash. As eschar is the most typical symptom of scrub typhus, it is often used to diagnose the disease, but if a patient does not display an obvious eschar lesion, diagnosing the disease can prove to be difficult. To help improve the diagnoses of scrub typhus, metagenomic next-generation sequencing (mNGS) has been used as a new approach to identifying pathogens. Here, we report a 51-year-old patient who had unexplained fever for a week and was admitted to hospital with no obvious eschar on her body. Smears and cultures of blood and sputum samples were first performed, but all returned a negative result for scrub typhus. We then conducted a mNGS analysis of blood and sputum samples and were able to identify the pathogenic microbe. Subsequently, a total of 377 reads, as well as 12 unique reads of Orientia tsutsugamushi were detected in the patient's blood and sputum. Quantitative polymerase chain reaction (qPCR) results of blood samples further confirmed our mNGS detection, suggesting that the patient did indeed have scrub typhus. From these results, we determined that mNGS as a diagnostic tool provides a better method of identifying clinical febrile pathogens with atypical characteristics.

Osteological development of a small and fast metamorphic frog, Microhyla fissipes (Anura, Neobatrachia, Microhylidae).

Describing osteological development is of great importance for understanding vertebrate phenotypic variations, form-functional transitions and ecological adaptations. Anurans exhibit dramatic changes in their morphology, habitat preferences, diet and behaviour between the tadpole and frog stages. However, the anatomical details of their cranial and postcranial development have not been extensively studied, especially in Microhylidae. In this work, we studied the microhylid Microhyla fissipes, commonly known as the ornamented pygmy frog, a small-sized frog with fast metamorphosis. Its osteological development was comprehensively described based on 120 cleared and stained specimens, including six tadpoles for each stage between 28 and 45, six juveniles and six adults. Additionally, 22 osteological traits of these specimens involved in food acquisition, respiration, audition and locomotion were selected and measured to reflect the changes in tadpole ecological functions during metamorphosis. Our study provides the first detailed qualitative and quantitative developmental information about these structures. Our results have confirmed that skeletal elements (viz., neopalatines, omosternum, clavicles and procoracoids) absent in adults are not detected during development. Our data reveal that morphologically, radical transformations of the cranial structures related to feeding and breathing are completed within stages 42-45 (72 h), but the relative length and width of these skeletons have changed in earlier stages. The postcranial skeletons correlated with locomotion are well developed before stage 42 and approach the adult morphology at stage 45. Indeed, the relative length of the pectoral girdle and forelimb reaches the adult level at stage 42 and stage 45, respectively, whereas that of the vertebral column, pelvic girdle and hind limbs increases from their appearance until reaching adulthood. Based on published accounts of 19 species from Neobatrachia, Mesobatrachia and Archaeobatrachia, cranial elements are among the first ossified skeletons in most studied species, whereas sphenethmoids, neopalatines, quadratojugals, mentomeckelians, carpals and tarsals tend to ossify after metamorphosis. These results will help us to better understand the ecomorphological transformations of anurans from aquatic to terrestrial life. Meanwhile, detailed morphological and quantitative accounts of the osteological development of Microhyla fissipes will provide a foundation for further study.

Association between Prognostic Nutritional Index and Contrast-Associated Acute Kidney Injury in Patients Complicated with Chronic Kidney Disease and Coronary Artery Disease.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a major adverse effect of coronary angiography (CAG). Patients with chronic kidney disease (CKD) and coronary artery disease (CAD) are at high risk of CA-AKI. This study aimed to investigate the association between prognostic nutritional index (PNI) and CA-AKI in this high-risk population. METHODS: This study enrolled a total of 4,391 patients. CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL or 50% from baseline within the first 48 hours following CAG. The PNI was calculated upon hospital admission: serum albumin (g/L) + 5 × total lymphocyte count (109/L). PNI was analysed from the high level to low level as a continuous variable and categorical variable which was divided into four groups by quartile. Restricted cubic splines and logistic regression were applied. RESULTS: Overall, 13.09% (575/4391) of patients developed CA-AKI. PNI score was significantly lower in patients with CA-AKI than that in patients without CA-AKI (P < 0.01). The relationship between PNI score and CA-AKI was linear. A logistic regression model revealed that decreased PNI score was associated with increased risk of CA-AKI [per 1-point decrement; adjusted OR = 1.08, 95% CI, 1.05-1.09; compared with Quartile 1 (PNI ≥ 46.30), Quartile 4 (PNI < 37.90), adjusted OR = 1.88, 95% CI: 1.41-2.51; and Quartile 3 (37.90 ≤ PNI < 42.15), adjusted OR = 1.37, 95% CI: 1.02-1.84]. CONCLUSION: Our study indicated a negative linear relationship between PNI score and CA-AKI in patients undergoing CAG complicated with CKD and CAD. It suggested that malnutrition is associated with increased risk of CA-AKI in this population.

Transcriptome sequencing reveals differential expression of circRNAs in sepsis induced acute respiratory distress syndrome.

circRNAs play important roles in regulating gene expression at both transcriptional and post transcriptional levels and involve in a variety of human diseases. But up to now, it is still unclear whether circRNAs are involved in the occurrence and development of sepsis induced acute respiratory distress syndrome (ARDS). In the present research, we collected lung tissues of sepsis induced ARDS patients (n = 3) and brain dead patients without ARDS (n = 3). From the results of genome-wide sequencing, a total of 272 significantly up-regulated and 231 significantly down-regulated circRNAs were obtained. Combining the previous sequencing results in the plasma of ARDS patients, 11 up-regulated and 3 down-regulated circRNAs simultaneously in plasma and lung tissues were identified. Pathway enrichment analysis showed that the co differentially expressed circRNAs might be involved in the regulation of ECM-receptor interaction and adherens junction etc. In conclusion, these data indicates that circRNAs may involve in the progression of sepsis induced ARDS.

Nutritional screening based on objective indices at admission predicts in-hospital mortality in patients with COVID-19.

BACKGROUND: Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. METHODS: A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. RESULTS: Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had significant differences in nutrition-related parameters and inflammatory biomarkers among three types of disease severity. Patients with lower GNRI and PNI, as well as higher CONUT scores, had a higher risk of in-hospital mortality. The receiver operating characteristic curves demonstrated the good prognostic implication of GNRI and CONUT score. The multivariate logistic regression showed that baseline nutritional status, assessed by GNRI, PNI, or CONUT score, was a prognostic indicator for in-hospital mortality. CONCLUSIONS: Despite variant screening tools, poor nutritional status was associated with in-hospital death in patients infected with COVID-19. This study highlighted the importance of nutritional screening at admission and the new insight of nutritional monitoring or therapy.