Nutrient deprivation induces mouse embryonic diapause mediated by Gator1 and Tsc2.

Embryonic diapause is a special reproductive phenomenon in mammals that helps embryos to survive various harsh stresses. However, the mechanisms of embryonic diapause induced by the maternal environment is still unclear. Here, we uncovered that nutrient deficiency in uterine fluid was essential for the induction of mouse embryonic diapause, shown by a decreased concentration of arginine, leucine, isoleucine, lysine, glucose and lactate in the uterine fluid of mice suffering from maternal starvation or ovariectomy. Moreover, mouse blastocysts cultured in a medium with reduced levels of these six components could mimic diapaused blastocysts. Our mechanistic study indicated that amino acid starvation-dependent Gator1 activation and carbohydrate starvation-dependent Tsc2 activation inhibited mTORC1, leading to induction of embryonic diapause. Our study elucidates the essential environmental factors in diapause induction.

Predictive value of Global Leadership Initiative on Malnutrition criteria combined with handgrip strength for postoperative outcomes in overweight colorectal cancer patients.

BACKGROUND AND AIM: The Global Leadership Initiative on Malnutrition (GLIM) criteria are increasingly used to assess the nutritional status of hospitalized patients and predict the prognosis of patients with malignant tumors; however, malnutrition is often overlooked in overweight individuals, such as colorectal cancer patients. This study aimed to investigate the predictive value of the GLIM criteria combined with handgrip strength (HGS) in overweight colorectal cancer patients. METHODS: This retrospective study enrolled overweight patients who underwent radical resection for colorectal cancer at two centers between 2015 and 2021. Malnutrition was diagnosed based on the GLIM criteria. Skeletal muscle mass was assessed using the skeletal muscle index, and skeletal muscle function was assessed using the HGS test. The risk factors for complications and survival were also evaluated. RESULTS: A total of 850 patients were enrolled in the study. The incidence of malnutrition in the GLIM and HGS-GLIM groups was 12.4% and 6.4%, respectively. The incidence of total complications in both the malnutrition groups was significantly higher than that in the control group. Patients in the HGS-GLIM-malnutrition group had worse overall survival and disease-free survival. HGS-GLIM was independently associated with postoperative complications (P = 0.046), overall survival (P = 0.037), and disease-free survival (P = 0.047). CONCLUSION: The GLIM criteria combined with the HGS test is an effective tool for diagnosing malnutrition. Particularly, these modalities are applicable in overweight colorectal cancer patients. Compared with the standard GLIM criteria, this tool has a better predictive value for postoperative complications and long-term survival.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC's RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.

Biogenic Solution Map Based on the Definition of the Metabolic Correlation Distance between 4-Dimensional Fingerprints.

Accurate discrimination and classification of unknown species are the basis to predict its characteristics or applications to make correct decisions. However, for biogenic solutions that are ubiquitous in nature and our daily lives, direct determination of their similarities and disparities by their molecular compositions remains a scientific challenge. Here, we explore a standard and visualizable ontology, termed "biogenic solution map", that organizes multifarious classes of biogenic solutions into a map of hierarchical structures. To build the map, a novel 4-dimensional (4D) fingerprinting method based on data-independent acquisition data sets of untargeted metabolomics is developed, enabling accurate characterization of complex biogenic solutions. A generic parameter of metabolic correlation distance, calculated based on averaged similarities between 4D fingerprints of sample groups, is able to define "species", "genus", and "family" of each solution in the map. With the help of the "biogenic solution map", species of unknown biogenic solutions can be explicitly defined. Simultaneously, intrinsic correlations and subtle variations among biogenic solutions in the map are accurately illustrated. Moreover, it is worth mentioning that samples of the same analyte but prepared by alternative protocols may have significantly different metabolic compositions and could be classified into different "genera".

Plasma transfusion in critically Ill patients with abnormal coagulation tests before invasive procedures: A propensity-adjusted cohort study.

OBJECTIVE: To evaluate the association between plasma transfusion and bleeding complications in critically ill patients with an elevated international normalized ratios undergoing invasive procedures. METHODS: A retrospective study was conducted to evaluate a consecutive sample of critically ill adult patients undergoing invasive procedures (N = 487) with an international normalized ratio ≥ 1.5 between January 1, 2019 and December 31, 2019. Among the followed patients, 125 were excluded due to incomplete case records and 362 were finally included in this investigation. The exposure was whether plasma had been transfused within 24 h before the invasive procedure. The primary outcome was the occurrence of postprocedural bleeding complications. Secondary outcomes included transfusion of red blood cells within 24 h of the invasive procedure, and additional patient-important outcomes such as mortality and length of stay. Tests were performed with univariate and propensity-matched analyses. RESULTS: Of the 362 study participants, 99 (27.3 %) received a preprocedural plasma transfusion. In the propensity score-matched analysis, the rate of the occurrence of postprocedural bleeding complications between two groups was not statistically different (OR, 0.605[95 % CI, 0.341-1.071]; P = .085). The rate of postoperative red blood cell transfusion in the plasma transfusion group was higher than that in the non-plasma transfusion group (35.5 % vs 21.5 %; P < .05). No statistically significant difference in mortality was observed between the two groups (29.0 % vs 31.6 %; P = .101). CONCLUSIONS: Prophylactic plasma transfusion failed to reduce postprocedural bleeding complications in ill critically patients with a coagulopathy. Meanwhile, it was associated with increased red blood cell transfusion after invasive procedures. Findings suggest that abnormal preprocedural international normalized ratios should be managed more conservatively.

EFFECT OF ANESTHESIA DURATION ON INTRAVITREAL INJECTION PAIN: A double-blinded, randomized, comparative study.

PURPOSE: To determine the effect of different durations of topical anesthesia on intravitreal injection (IVI) pain. METHODS: This was a double-blinded, randomized, comparative study . Three hundred and twelve sequential eyes undergoing IVI were randomized to one of six groups according to the duration of topical anesthesia (from 1 to 30 minutes, one group for every 5-minute range, Groups 1-6). Topical anesthesia before IVI was standardized. Patients graded their pain using the visual analog scale and the Wong-Baker FACES scale at 15 minutes after the procedure. RESULTS: The pain scores among the six groups were significantly different for the visual analog scale ( P = 0.013) and Wong-Baker FACES scale ( P = 0.024). The mean pain scores for Group 4 were 1.97 ± 1.04 (visual analog scale) and 2.02 ± 1.08 (Wong-Baker FACES scale) and were significantly lower than those of Group 1, 2, 5, or 6. CONCLUSION: The duration of topical anesthesia significantly correlated with IVI pain. Preoperative 0.5% proparacaine hydrochloride drops were most effective in relieving IVI pain 11 to 20 minutes after topical administration.

Smartphone-Enabled Fluorescence and Colorimetric Platform for the On-Site Detection of Hg2+ and Cl- Based on the Au/Cu/Ti3C2 Nanosheets.

Smartphone-assisted fluorescence and colorimetric methods for the on-site detection of Hg2+ and Cl- were established based on the oxidase-like activity of the Au-Hg alloy on the surface of Au/Cu/Ti3C2 NSs. The Au nanoparticles (NPs) were constructed via in-situ growth on the surface of Cu/Ti3C2 NSs and characterized by different characterization techniques. After the addition of Hg2+, the formation of Hg-Au alloys could promote the oxidization of o-phenylenediamine (OPD) to generate a new fluorescence emission peak of 2,3-diaminopenazine (ADP) at 570 nm. Therefore, a turn-on fluorescence method for the detection of Hg2+ was established. As the addition of Cl- can influence the fluorescence of ADP, the fluorescence intensity was constantly quenched to achieve the continuous quantitative detection of Cl-. Therefore, a turn-off fluorescence method for the detection of Cl- was established. This method had good linear ranges for the detection of Hg2+ and Cl- in 8.0-200.0 nM and 5.0-350.0 µM, with a detection limit of 0.8 nM and 27 nM, respectively. Depending on the color change with the detection of Hg2+ and Cl-, a convenient on-site colorimetric method for an analysis of Hg2+ and Cl- was achieved by using digital images combined with smartphones (color recognizers). The digital picture sensor could analyze RGB values in concentrations of Hg2+ or Cl- via a smartphone app. In summary, the proposed Au/Cu/Ti3C2 NSs-based method provided a novel and more comprehensive application for environmental monitoring.

Screening differential circular RNA expression profiles reveals the regulatory role of circMARS in anti-tuberculosis drug-induced liver injury.

Tuberculosis (TB) treatment is plagued by liver damage, which often leads to treatment interruptions. Circular RNAs (circRNAs) are a special class of non-coding RNAs abundant in body fluids with important biological functions. However, the role of circRNA in anti-tuberculosis drug-induced liver injury (ADLI) is unclear. We explored ADLI-specific circRNAs in TB patients using circRNA microarrays and verified circMARS in a cohort of 300 individuals. In addition to the value assessment of circMARS in patients using a receiver operating characteristic (ROC) curve, cell experiments were also performed under the guidance of bioinformatics analyses. In particular, we found that circMARS acts as a miRNA sponge by binding to miRNAs. Compared with the blank group, the expressions of circMARS, KMT2C gene, and EGFR protein in the ADLI group were increased, while miR-6808-5p, miR-6874-3p, and miR-3157-5p were decreased. Furthermore, when si-circMARS was used in the ADLI groups, circMARS demotion manifested the opposite results. Subsequently, a self-controlled cohort of 35 participants was used to verify the circMARS-miR-6808-5p/-6874-3p/-3157-5p-KMT2C-EGFR function axis. Therefore, circMARS may participate in the compensatory repair mechanism of ADLI through the function axis, and may be a potential biomarker for ADLI diagnosis in TB patients.

Evaluation of crossed cerebellar diaschisis after cerebral infarction in MCAO rats based on DKI.

OBJECTIVE: To observe the expression of N-methyl-D-aspartate (NMDA), apoptosis and the effect on neurological function recovery in rat model with middle cerebral artery occlusion (MCAO). Diffusion kurtosis imaging (DKI) was used to evaluate crossed cerebellar diaschisis (CCD) and to provide experimental and theoretical basis for the clinical treatment. MATERIALS AND METHODS: The MCAO models were established in rats. Eighty-four rats were randomly and evenly divided into 7 groups, including control group, 6-h group, 12-h group, 24-h group, 48-h group, 7-day group and 14-day group. The rats were scanned by MRI at the above time points. Then, rats were sacrificed for H&E staining, immunohistochemical staining and TUNEL staining to detect the expression of NMDA in the core infarct area and cerebellum. At the end, the discussion of relationships between molecular biology and MRI parameters (ADC derived from DWI, and MD, MK and FA derived from DKI) was performed. RESULTS: The values of MD, ADC and FA in MCAO rats were all lower than those in the control group. All MRI parameters of the contralateral cerebellum were lower than those of the ipsilateral cerebellum (p < .05). The parameters reached the lowest value at 12 h, except that the MK reached the highest at 12 h. The expression of NMDA showed a fluctuation along time in the MCAO group. Overall, it is higher in the MCAO group than in the control group, reaching the maximum at 24 h (p < .05). At the same time, the expression of NMDA in the contralateral cerebellum was higher than in the ipsilateral cerebellum. CONCLUSION: It is found that NMDA and DKI of CCD have the same changing trend, which indicates that the intervention of NMDA receptor apoptosis may become a new target for the treatment of cerebral infarction, and MRI parameters can predict the occurrence and development of CCD.

The role of PTEN in puromycin aminonucleoside-induced podocyte injury.

Podocytes are specialized cells of the glomerulus that play important structural and functional roles in maintaining the filtration barrier. Loss and injury of podocytes are leading factors of glomerular disease and kidney failure. Recent studies found that phosphatase and tensin homolog (PTEN) may play a critical role in maintaining the normal structure and function in podocytes. However, we still understand very little about how PTEN is regulated under podocyte injury conditions. In this study, We therefore investigated whether PTEN could play a role in podocyte injury induced by puromycin aminonucleoside (PAN), and whether dexamethasone (DEX) alleviates podocyte injury by PTEN/PI3K/Akt signaling. Our results showed that PI3K/Akt pathway was activated in podocytes exposed to PAN conditions, accompanied by down-regulation of the PTEN and microtubule-associated light chain 3 (LC3) expression.podocyte-specific knockout of PTEN significantly promoted podocyte injury, The potential renoprotection of overexpressed PTEN in podocytes was partly attributed with an improvement in autophagy and the inhibition of apoptosis.These novel findings also suggest that targeting PTEN might be a novel and promising therapeutic strategy against podocyte injury.

Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

A possible dose-response equation: Viral load after plasma infusion in COVID-19 patients and anti-SARS-CoV-2 antibody titers in convalescent plasma.

BACKGROUND: Clinical trials of convalescent plasma therapy for coronavirus disease 2019 (COVID-19) are extensive, but the relationship between antibody titers, infused volume of plasma and virus clearance in patients remains unknown. This study proposed a possible estimating equation for clinical use of high antibody titer convalescent plasma. METHODS: A total of 38 patients were recruited in the Guanggu District Maternal and Child Health Hospital of Hubei Province from March 1 to 30, 2020. COVID-19 convalescent plasma was collected and high-titer (≥1:640) anti-S-RBD units used. The SARS-CoV-2 nucleic acid viral load was measured 24 h before and 72 h after convalescent plasma infusion. RESULTS: Convalescent plasma therapy was associated with reduced viral load in patients with moderate and severe severity. The viral negative rate at 72 h was 65.8%. The disappearance of viral nucleic acid in study patients was positively correlated with infuscate antibody titer and volume (r = 0.3375, p = 0.04). A possible estimation equation was as follows: Log10 (Reduction in viral load) = 0.18 + 0.001 × (Log2 S-RBD antibody titer × Plasma infusion volume) (r = 0.424, p = 0.009). In a single case, the viral nucleic acid persisted 14 days after the fourth plasma infusion. CONCLUSIONS: This study proposes a potential dose-response equation that adds a convenient way to estimate the dose of convalescent plasma product. It is beneficial to facilitate the rational allocation of plasma with high antibody titers and provide an individualised use strategy for convalescent plasma therapy.

Vitronectin, a Novel Urinary Proteomic Biomarker, Promotes Cell Pyroptosis in Juvenile Systemic Lupus Erythematosus.

Objective: Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE). Methods: The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis. Results: Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. Conclusion: This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.

Interaction between the HIF-1α gene rs1957757 polymorphism and CpG island methylation in the promoter region is associated with the risk of anti-tuberculosis drug-induced liver injury in humans: A case-control study.

WHAT IS KNOWN AND OBJECTIVE: HIF-1α gene polymorphisms, including rs11549465, rs11549467, rs1957757 and rs10873142, cause liver cell damage or pulmonary disease. The aim of this study was to analyse the association between the polymorphisms of the loci of the HIF-1α gene and its CpG island methylation in the promoter region with the risk of anti-tuberculosis drug-induced liver injury (ADLI). METHODS: 286 patients with tuberculosis (TB) and ADLI (case group) and 286 patients with TB but without liver injury (control group) were matched one-to-one, among the 1728 TB patients recruited from July 2019 to July 2020. Genotyping of the four loci of the HIF-1α gene was confirmed using PCR-RFLP technology. Methylation of the HIF-1α gene was measured using the MSP method. The comparison of risk factors, HIF-1α genotype and methylation status between the case group and the control group was all achieved through univariate and multivariate conditional logistic regression. RESULTS AND DISCUSSION: Univariate analysis showed that the frequency of rs1957757 mutation genotype and CpG island methylation was significantly higher in the case group than in the control group (P<0.001, all). In contrast, there was no statistical difference in the frequency of mutated genotypes at the other three loci between the two groups (p = 0.21, p = 0.12 and p = 0.55, respectively). Further, multivariate analysis showed that CpG islands were methylated, the mutation genotype of the rs1957757 locus was independently associated with the high risk of ADLI, and the adjusted OR (95%CI) reached 1.92 (1.32-2.63) and 2.01 (1.32-2.83), respectively. Furthermore, taking the rs1957757 locus wild genotype and CpG islands without methylation as the reference group, the mutation genotype and CpG island methylation increased the risk of ADLI, and the probability of ADLI could reach 4.73 times that of the reference group. WHAT IS NEW AND CONCLUSION: This is the first demonstration of the association of HIF-1α gene polymorphism and CpG island methylation with ADLI risk stratification. The interaction between CpG islands methylated in the promoter region of the HIF-1α gene and its rs1957757 locus mutant genotype was associated with a higher risk of ADLI.

Effects of a standardized patient-based simulation in anaphylactic shock management for new graduate nurses.

BACKGROUND: Patients may be endangered if new graduate nurses cannot recognize and manage anaphylactic shock. Consequently, enhancing the new graduate nurses' understanding of their roles and responsibilities during the rescue of a patient with anaphylactic shock is important. However, due to its inherent limitations, traditional classroom-based teaching makes it difficult to explore the potential of the students. Although popular simulation teaching has several notable advantages, it has not been proven to be effective in training inexperienced nurses on anaphylactic shock. We investigated the effect of a standardized patient-based simulation on the behaviors of new graduate nurses' during anaphylactic shock rescue to identify an effective and safe method for contemporary nursing education. METHODS: Except for the ill or pregnant, all the new graduate nurses were included in the study as students to undergo a standardized patient-based simulation conducted in the clinical skills center of a general hospital. The simulation training was designed to teach students to recognize the signs and symptoms of anaphylactic shock, place the patient in the correct position, stop the ongoing intravenous infusion of the antibiotic which triggers the anaphylactic shock, restart an intravenous infusion on a new infusion apparatus, give 100% oxygen via a nasal cannula or mask, preserve airway patency, call the rapid response team, and correctly administer the medications prescribed by the clinicians. Before and after the training, the instructors evaluated each student's skills and behaviors using a clinical competency evaluation list. After the training, all students completed the Chinese version of the Simulation Design Scale (SDS) to demonstrate their satisfaction with the program and then participated in semi-structured interviews with their instructors. RESULTS: All 104 graduate nurses had a significant improvement on the 6 competencies of the clinical competency evaluation list after the simulation training (P < 0.001). The SDS scores revealed that the students were highly satisfied with all the aspects of the simulation training (the 20 satisfaction rates were all above 90.00%). During the semi-structured interviews, most of the new graduate nurses reported that simulation training in the management of anaphylactic shock was critical and would guide them in clinical practice. CONCLUSION: Simulation training in anaphylactic shock is a potentially viable and effective method for teaching new graduate nurses to manage clinical incidents.

CRB-SWATH: A Method for Enhancing Untargeted Precursor Ion Extraction and Automatically Constructing Their Tandem Mass Spectra from SWATH Datasets by Chromatographic Retention Behaviors.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions. Thus, although their product ions could be acquired, their precursor ions are absent. Here, we present a new strategy, chromatographic retention behavior-SWATH (CRB-SWATH), that could unbiasedly capture poor-quality peaks and provide high resolutions of multiplexed mass spectroscopy (MS/MS) spectra in SWATH datasets. CRB-SWATH monitors CRBs of SWATH-MS signals under a series of altered elution gradients. As signals of compounds differ from noise by showing CRBs, both the precursor and fragment ions are captured, while ignoring their peak qualities. Moreover, CRB-SWATH offers good chances to resolve highly multiplexed MS/MS spectra in SWATH datasets because precursor ions coeluted in a single elution gradient often present different CRBs. In the untargeted metabolic analysis of Hela cell extracts, CRB-SWATH showed the advantage in exclusively capturing 2645 ions of poor-quality peaks (i.e., tiny peaks, discontinuous ion traces, tailing peaks, zigzag peaks, etc.), accounting for 34.4% of all the untargeted precursor ions extracted. Therein, it is noteworthy that among 2116 negative ions detected in hydrophilic interaction liquid chromatography (HILIC) mode, 1284 poor-quality ion peaks (>60%) were exclusively captured by CRB-SWATH. As CRB-SWATH automatically captures a large sum of true ion peaks of poor qualities, extracts MS/MS spectra of high purities, and provides chromatographic retention behaviors of untargeted metabolites for identification and classification, it could be a useful metabolomics tool for understanding biological phenomena better.

De Ritis Ratio as a Significant Prognostic Factor in Patients with Sepsis: A Retrospective Analysis.

PURPOSE: This study was performed to investigate the relationship between the aspartate transaminase and/or alanine transaminase ratio (DRR) and long-term mortality of patients diagnosed with sepsis or septic shock. MATERIALS AND METHODS: We conducted a retrospective study among adult septic patients who were admitted to the surgical intensive care unit (ICU) of the Chinese People's Liberation Army (PLA) General Hospital from January 2014 to December 2018. Baseline characteristics were compared between survivors and non survivors. We performed univariate and multivariate Cox regression analyses to evaluate the relation of DRR with 180-day mortality. The potential prognostic value of DRR in predicting mortality rate was assessed by receiver operating characteristic (ROC) curve analysis. In addition, we conducted subgroup analysis by the optimal DRR cutoff value. RESULTS: We included a total of 183 patients in the current study, and 44 (24%) patients died within 180 days of hospitalization. Univariate and multivariate Cox analyses revealed that DRR was an independent predictor of 180-day mortality (hazard ratio [HR] 1.421, 95% confidence interval [CI] 1.073-1.883, P = 0.014). The predictive accuracy of DRR for 180-day mortality was presented as an ROC curve, which had an area under the curve (AUC) of 0.708 (95% CI 0.629-0.786, P < 0.001). After we stratified all enrolled patients into two groups by using the optimal cutoff value of 1.29, we observed a significantly higher mortality in patients with a relatively high DRR. CONCLUSIONS: An elevated DRR was associated with higher 180-day mortality among septic patients, and DRR might be an optimal marker for predicting the long-term mortality of sepsis. More prospective and randomized trials are needed to confirm the prognostic value of DRR.