Methodological validation of sedimentation velocity analytical ultracentrifugation method for Adeno-Associated Virus and collaborative calibration of system suitability substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and High Sedimentation Coefficient Substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF( high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the RSD (relative standard deviation) could be within 5%. Even for empty or partial less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4×1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Due to the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control)laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

The effect of instant tea on the aroma of duck meat.

Tea products, such as instant tea, have been shown to improve the aroma of meat products. However, the mechanisms by which tea products enhance meat aroma have not been adequately explained. In this study, we analyzed the impact of instant tea on the aroma of duck meat. Our results showed that treatment with instant tea led to increases in floral, baked, and grassy notes while reducing fishy and fatty notes. Several alcohols, aldehydes, ketones, indole and dihydroactinidiolide exhibited significantly increased OAVs. Conversely, certain saturated aldehydes, unsaturated aldehydes and alcohols displayed significantly decreased OAVs. The enhanced floral, baked and grassy notes were attributed to volatile compounds present in instant tea. The reduction in fishy and fatty notes was linked to polyphenols in instant tea interacting with nonanal, undecanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal, and 2,4-decadienal through hydrophobic interactions and electronic effects. This study enhances our understanding of how tea products improve meat aromas.

Towards a biomimetic cellular structure and physical morphology with liposome-encapsulated agarose sol systems.

The cytoplasm, serving as the primary hub of cellular metabolism, stands as a pivotal cornerstone for the harmonious progression of life. The ideal artificial cell should not only have a biomembrane structure system similar to that of a cell and the function of carrying genetic information, but also should have an intracellular environment. In this pursuit, we employed a method involving the incorporation of glycerol into agarose, resulting in the formation of agarose-glycerol mixed sol (AGs). This dynamic sol exhibited fluidic properties at ambient temperature, closely mimicking the viscosity of authentic cytoplasm. Harnessing the electroformation technique, AGs was encapsulated within liposomes, enabling the efficient creation of artificial cells that closely resembled native cellular dimensions through meticulous parameter adjustments of the alternating current (AC) field. Subsequently, artificial cells harboring AGs were subjected to diverse electrolyte and non-electrolyte solutions, enabling a comprehensive exploration of their deformation phenomena, encompassing both inward and outward budding. This study represents a significant stride forward in addressing one of the most fundamental challenges in the construction of artificial cytoplasm. It is our fervent aspiration that this work shall offer invaluable insights and guidance for future endeavors in the realm of artificial cell construction.

Early-life perfluorooctanoic acid exposure disrupts the function of dopamine transporter protein with glycosylation changes implicating the links between decreased dopamine levels and disruptive behaviors in larval zebrafish.

Exposure to perfluorooctanoic acid (PFOA) during early embryonic development is associated with the increased risk of developmental neurotoxicity and neurobehavioral disorders in children. In our previous study, we demonstrated that exposure to PFOA affected locomotor activity and disrupted dopamine-related gene expression in zebrafish larvae. Consequently, we continue to study the dopaminergic system with a focus on dopamine levels and dopamine's effect on behaviors in relation to PFOA exposure. In the present study, we found a decrease in dopamine levels in larval zebrafish. We studied the dopamine transporter (DAT) protein, which is responsible for regulating dopamine levels through the reuptake of dopamine in neuronal cells. We demonstrated that exposure to PFOA disrupted the glycosylation process of DAT, inhibited its uptake function, and induced endoplasmic reticulum (ER) stress in dopaminergic cells. Besides, we conducted a light-dark preference test on larval zebrafish and observed anxiety/depressive-like behavioral changes following exposure to PFOA. Dopamine is one of the most prominent neurotransmitters that significantly influences human behavior, with low dopamine levels being associated with impairments such as anxiety and depression. The anxiety-like response in zebrafish larvae exposure to PFOA implies the link with the reduced dopamine levels. Taken together, we can deduce that glycosylation changes in DAT lead to dysfunction of DAT to regulate dopamine levels, which in turn alters behavior in larval zebrafish. Therefore, alternation in dopamine levels may play a pivotal role in the development of anxiety/depressive-like behavioral changes induced by PFOA.

Characterization of the off-flavor from Pichia pastoris GS115 during the overexpression of an α-l-rhamnosidase.

The off-flavor of Pichia pastoris strains is a negative characteristic of proteins overexpressed with this yeast. In the present study, P. pastoris GS115 overexpressing an α-l-rhamnosidase was taken as the example to characterize the off-flavor via sensory evaluation, gas chromatography-mass spectrometer, gas chromatography-olfaction, and omission test. The result showed that the off-flavor was due to the strong sweaty note, and moderate metallic and plastic notes. Four volatile compounds, that is, tetramethylpyrazine, 2,4-di-tert-butylphenol, isovaleric acid, and 2-methylbutyric acid, were identified to be major contributors to the sweaty note. Dodecanol and 2-acetylbutyrolactone were identified to be contributors to the metallic and plastic notes, respectively. It is the first study on the off-flavor of P. pastoris strains, helping understand metabolites with off-flavor of this yeast. Interestingly, it is the first study illustrating 2-acetylbutyrolactone and dodecanol with plastic and metallic notes, providing new information about the aromatic contributors of biological products. IMPORTANCE: The methylotrophic yeast Pichia pastoris is an important host for the industrial expression of functional proteins. In our previous studies, P. pastoris strains have been sniffed with a strong off-flavor during the overexpression of various functional proteins, limiting the application of these proteins. Although many yeast strains have been reported with off-flavor, no attention has been paid to characterize the off-flavor in P. pastoris so far. Considering that P. pastoris has advantages over other established expression systems of functional proteins, it is of interest to identify the compounds with off-flavor synthesized in the overexpression of functional proteins with P. pastoris strains. In this study, the off-flavor synthesized from P. pastoris GS115 was characterized during the overexpression of an α-l-rhamnosidase, which helps understand the aromatic metabolites with off-flavor of P. pastoris strains. In addition, 2-acetylbutyrolactone and dodecanol were newly revealed with plastic and metallic notes, enriching the aromatic contributors of biological products. Thus, this study is important for understanding the metabolites with off-flavor of P. pastoris strains and other organisms, providing important knowledge to improve the flavor of products yielding with P. pastoris strains and other organisms. ONE-SENTENCE SUMMARY: Characterize the sensory and chemical profile of the off-flavor produced by one strain of P. pastoris in vitro.

Perfluorooctanoic acid disrupts thyroid-specific genes expression and regulation via the TSH-TSHR signaling pathway in thyroid cells.

Perfluorooctanoic acid (PFOA) is a highly persistent and widespread chemical in the environment with endocrine disruption effects. Although it has been reported that PFOA can affect multiple aspects of thyroid function, the exact mechanism by which it reduces thyroxine levels has not yet been elucidated. In this study, FRTL-5 rat thyroid follicular cells were used as a model to study the toxicity of PFOA to the genes related to thyroid hormone synthesis and their regulatory network. Our results reveal that PFOA interfered with the phosphorylation of the cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) induced by thyroid-stimulating hormone (TSH), as well as the transcription levels of paired box 8 (PAX8), thyroid transcription factor 1 (TTF1), sodium/iodide cotransporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO). However, the above outcomes can be alleviated by enhancing cAMP production with forskolin treatment. Further investigations showed that PFOA reduced the mRNA level of TSH receptor (TSHR) and impaired its N-glycosylation, suggesting that PFOA has disrupting effects on both transcriptional regulation and post-translational regulation. In addition, PFOA increased endoplasmic reticulum (ER) stress and decreased ER mass in FRTL-5 cells. Based on these findings, it can be inferred that PFOA disrupts the TSH-activated cAMP signaling pathway by inhibiting TSHR expression and its N-glycosylation. We propose that this mechanism may contribute to the decrease in thyroid hormone levels caused by PFOA. Our study sheds light on the molecular mechanism by which PFOA can disrupt thyroid function and provides new insights and potential targets for interventions to counteract the disruptive effects of PFOA.

Development and internal validation of a practical model to predict 30 days mortality of severe acute pancreatitis patients.

BACKGROUND: Severe acute pancreatitis (SAP) is a common disease in the intensive care unit (ICU) accompanied by high mortality, the purpose of this study was to build a prediction model for the 30 days mortality of SAP. METHODS: We retrospectively reviewed 149 patients with SAP after admission in 48 h to the ICU of the First Affiliated Hospital of Nanjing Medical University between January 2015 and December 2019. Clinical variables including gender, age, blood routine, and biochemical indicators were collected. On the basis of these variables, stepwise regression analysis was carried out to establish the model. A bootstrapping technique was applied for internal validation. RESULTS: Age, aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglycerides (TG), and creatinine (CREA) were differences between survivors and nonsurvivors groups (all p < 0.1). Multivariate analysis suggested that age, AST, ALP, TG, and CREA were independent variables. Then, a model was established. The area-under-the curve (AUC) of the model was 0.875 (95% confidence interval (CI): 0.811-0.924). After internal validation, the C-index was 0.859 (95% CI: 0.786-0.932). CONCLUSION: Our study has built a refined model with easily acquired biochemical parameters to predict 30 days mortality of SAP admitted to ICU. This model will require external and prospective validation prior to translate into clinical management.

Severe acute pancreatitis is a common disease in the intensive care unit with high mortality.A prediction model for the 30 days mortality of SAP was built with easily acquired parameters.

Precise Electron-Withdrawing Strength Modulation of ESIPT Probes for Ultrasensitive and Specific Fluorescence Sensing.

The precise regulation of the electron-withdrawing/electron-donating strength in a probe is of great significance for the design of reaction-based fluorescent probes with specific functionalities. Here, a family of excited-state intramolecular proton transfer (ESIPT)-based probes with fluorescence turn-on sensing properties toward KMnO4 was designed by precisely modulating the electron-withdrawing strength of the substituents located at the para-position of the recognition group. It is found that -F, -CHO, and -H as the electron-withdrawing groups bound at the probe can specifically recognize KMnO4, which ensures a blue emission displayed by the reaction products. Especially with -CHO as the electron-withdrawing group, the reaction product shows the most stable fluorescence. The probe 2-(benzo[d]oxazol-2-yl)-4-formylphenyl acrylate (BOPA-CHO) demonstrated a more superior sensing performance toward KMnO4, including a low limit of detection (LOD, 0.96 nM), a rapid response (<3 s), and a rather good selectivity even in the presence of 21 interferents. Moreover, the practicality of the probe was further verified by a test pen comprising a BOPA-CHO-embedded sponge, which is capable of detecting KMnO4 solid with a naked-eye LOD of 11.62 ng. The present probe design and modulation strategy would open up a new path for the design of high-performance fluorescent probes.

Dual responsive self-healing hydrogels with wide stability and excellent mechanical strength based on aliphatic polycarbonate.

The wide development of hydrogels had been used in many filed due to the high water-containing and tough three-dimensional structure, however, the poor mechanical and multi-functional properties of hydrogel can be limited in its applications deeply. Herein, the dual responsive self-healing hydrogels with tough mechanical properties were manufactured by dual-physical cross-linking based on biodegradable aliphatic polycarbonate. Choosing the soft and hard segments to design the polymeric hydrogel not only can facilitate the dual-dynamic bonding interactions but also the resilient hydrogels possess robust and controllable mechanical strength (6.51 MPa). Furthermore, the results of swelling and stability tests of the materials indicated that the swelling ability of the biodegradable hydrogels can be regulated by the hydrophilic group, and the maximal swelling ratio in water and the equilibrium water content is 66% and 40%, respectively. It is worth mentioning that the tough hydrogels embrace dual-responsive high efficiency of self-healing ability, and the self-healing time is 2 h at 50 °C or 10 h under pH = 5, suggesting that the obtained hydrogels can respond to temperature and pH value to drive the fracture interface for fast self-healing, which will offer new opportunities for stimuli-responsive materials and wound healing.

The effect of ozone short-term exposure on flow-mediated dilation: Using data before and after COVID-19 lockdown in Shanghai.

BACKGROUND: Short-term ambient ozone exposure has been shown to have an adverse impact on endothelial function, contributing to major cardiovascular diseases and premature death. However, only limited studies have focused on the impact of short-term ozone exposure on Flow-mediated Dilation (FMD), and their results have been inconsistent. The current study aims to explore the relationship between short-term ambient ozone exposure and FMD. In addition, the study aims to investigate how lockdown measures for COVID-19 may influence ozone concentration in the atmosphere. METHODS: Participants were recruited from a hospital in Shanghai from December 2020 to August 2022. Individuals' ozone exposure was determined using residential addresses. A distributed lag nonlinear model was adopted to assess the exposure-response relationship between short-term ozone exposure and FMD. A comparison was made between ambient ozone concentration and FMD data collected before and after Shanghai's lockdown in 2022. RESULTS: When ozone concentration was between 150 and 200 µg/m3, there was a significant reduction in FMD with a 2-day lag. Elderly individuals (age ≥ 65), females, non-drinkers, and non-smokers were found to be more susceptible to high concentrations of ozone exposure. The lockdown did elevate ambient ozone concentration compared to the same period previously. INTERPRETATION: This study proposes that an ambient ozone concentration of 150-200 µg/m3 is harmful to endothelial function, and that a reduction in human activity during lockdown increased the concentration, which in turn reduced FMD. However, the underlying mechanism requires further research.

A TD-DFT study of a class of D-π-A fluorescent probes for detection of typical oxidants.

A deep understanding of the fluorescence response mechanisms is the foundation for design-oriented strategies for D-π-A probes for trace hazardous chemicals. Here, from the perspective of electronegativity regulation of the π-bridge recognition site, an electron-donation modulation strategy involving various comprehensive evaluations of the optical and chemical properties is proposed through a series of theoretical analyses. Due to the preferential combined interaction between the π-bridge recognition site and MnO4-, high electrophilic reactivity and feasible chemical reaction energy barrier, a high-performance filter paper chip and hydrogel chip for the detection of aqueous and air-suspended environmental KMnO4 was achieved. We expect the present modulation strategy will facilitate efficient fluorescent probe design and provide a universal methodology for the exploration of functional D-π-A molecules.

Polyethyleneimine-capped copper nanoclusters for detection and discrimination of 2,4,6-trinitrotoluene and 2,4,6-trinitrophenol.

The detection and discrimination of 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenol (TNP) from analogues are of great importance to global security and are full of challenges in the field of trace sensing. Here, benefitting from the strong electrophilicity of TNT, a sensing strategy is established by synthesizing polyethyleneimine capped copper nanoclusters (PEI-Cu NCs) with abundant -NH2 groups. By carefully controlling the size and structure of PEI-Cu NCs, Förster resonance energy transfer (FRET) from PEI-Cu NCs to the Meisenheimer complex occurs resulting from their spectral overlap when detecting TNT, while, due to the energy level match of TNP with PEI-Cu NCs, as well as the strong affinity between its -OH and -NH2 in PEI-Cu NCs, photo-induced electron transfer (PET) is feasibly expected. As a result, TNT and TNP could be detected from 26 types of analogues and cations with a limit of detection (LOD) of 26.57 and 12.82 nM, respectively. Besides, owing to the brown color of the Meisenheimer complex, the discrimination of TNT and TNP could be additionally realized by colorimetric detection. We expect that the proposed methodology would not only shine light on the detection and discrimination of TNT and TNP that mitigate against public security concerns, but also pave a way for the deep understanding of FRET and PET related fluorescence quenching mechanisms from the aspect of controllable sensing material design and synthesis.

Complete Inhibition of the Rotation in a Barrierless TICT Probe for Fluorescence-On Qualitative Analysis.

Inhibition of twisting intramolecular charge transfer (TICT) is one of the most attractive methods for fluorescence-on analysis, whereas it remains enigmatic whether the fluorescence in a TICT-based probe could be thoroughly lightened. Here, for maximizing the fluorescence-on signal of the TICT-based probe, we develop a model by employing chemical reaction to directly cleave the linkage between the rotational electron donor and acceptor with a predisposed fluorescent signal close to zero. To validate this assumption, a nonfluorescent probe with barrierless rotation is successfully achieved by grafting acryloyl with -C═C- recognition sites onto coumarin, and 7-hydroxycoumarin with bright blue fluorescence could be released within 3 s upon probing KMnO4 with an amount as low as 0.95 nM and 6.6 pg. We believe that the present strategy could not only deepen the insights of photochemistry but also facilitate the development of a theranostic drug delivery system, energy conversion, pollution control, and health risk reduction.

Effects of mindfulness in patients with mild cognitive impairment with insomnia: A double-blind randomized controlled trial.

OBJECTIVE: Current research on the effects of mindfulness therapy on MCI and insomnia has been inconsistent. It is still a hot topic of research and discussion. This study aimed to improve the sleep quality, cognition, and mental state of patients with mild cognitive impairment (MCI) with insomnia. METHODS: A double-blind randomized controlled trial was conducted. Seventy-five patients who met the eligibility criteria were randomly assigned to the mindfulness (n = 38) or health education (n = 37) treatment group. The primary outcomes were sleep, measured by the Pittsburgh Sleep Quality Inventory, and cognition, measured by The Montreal Cognitive Assessment and Mini-Mental State Examination. Secondary outcomes included insomnia, measured by the Insomnia Severity Index, depression, anxiety, and perceived stress. EEG signals were collected at rest with eyes closed in the mindfulness state. The power spectrum was analyzed from these data. RESULTS: Cognitive function and sleep quality were significantly improved in the mindfulness group (95% confidence interval 0.04 - 0.05, 0.03 - 0.04, -5.58 - -1.55, respectively). Anxiety and perceived stress scores were significantly lower than those in the control group (95% confidence interval 0.002 - 0.004, 0.009 - 0.013, respectively). The power spectrum differences in δ, θ, ß, and γ bands were significant between the rest and mindfulness states (P < .05). Good safety was achieved in both groups with no deaths or serious adverse events. CONCLUSION: Mindfulness improved sleep quality, cognitive function, and mentality of patients. Mindfulness practice caused deep relaxation in the brain and changes in electrical frequency bands associated with attention and cognitive tasks. Mindfulness learning can be performed successfully for individuals with MCI. Additionally, it is suitable for adoption in nursing homes.

Developing a professional-practice-model-based nursing organizational informatics competency model.

BACKGROUND: The development of nursing informatics started late in China. There is an urgent need to develop a clinical practice model that can guide nursing managers in constructing an organizational nursing informatics competency. OBJECTIVE: The objective of this study was to develop a nursing organizational informatics competency model based on the Professional Practice Model (PPM) and to provide a reference for training in clinical nursing informatics in hospitals. METHODS: A multidisciplinary team in the hospital was first formed as the working group, consisting of nurses trained with the TIGER (Technology Informatics Guiding Education Reform) Taiwan model and had practical experience in system development. We used an exploration map to help build the prototype of the hospital nursing informatics competency model. Then, a final model was constructed by experienced out-of-hospital experts using the Delphi method. The final model was determined according to the validity analysis. RESULTS: Ten hospital stakeholders were invited to form the multidisciplinary working team to develop the prototype organizational PPM model. Two rounds of Delphi were conducted to twelve experienced nurses' informatics experts outside the hospital by e-mail. The results showed that the questionnaire return rate was 100 %, the expert authority coefficient was 0.84, the general validity of the two rounds of content was 92.46 % and 100 %, respectively, and the coefficient of variation of all items was < 0.3. The final model included five categories, including management strategy and leadership, organizational structure and operation, improvement of the environment for nursing information practice, cultivation of core competence in nursing information, and project management of the nursing information system, with 61 elements in total. CONCLUSIONS: We propose this model to help hospital nursing managers to establish a plan of action to build up organizational clinical informatics competency.

D-π-A Dual-Mode Probe Design for the Detection of nM-Level Typical Oxidants.

Although a set of functional molecules with the D-π-A structure has been explored as optical probes for the detection of target analytes, it remains a great challenge to elaborately design a single probe for distinguishing different analytes by their intrinsic oxidation or reduction capabilities and thus to generate distinct optical responses. Here, a unique TCF-based probe (DMA-CN) containing two unsaturated double bonds in the π-conjugation bridge and TCF with different reaction activities that could be cut off by KMnO4 and NaClO in varying degrees was developed, causing remarkably distinguishable responses for both fluorescence and colorimetric channels to discriminate KMnO4 and NaClO from each other. The fluorescence and colorimetric limits of detection (LODs) of the proposed DMA-CN toward KMnO4 were calculated as 60 and 91 nM, respectively, while those for NaClO were 13.3 and 214 nM, and all the optical signal change can be observed within 1 s with good specificity. Based on the proposed probe design strategy, a well-fabricated test strip was proven to be promising for the rapid, in-field detection and risk management. We expect that the present probe design methodology would provide a powerful strategy for efficient probe exploration, especially for discriminating the substances with similar oxidizing properties.

Perfluorooctanoic acid exposure increases both proliferation and apoptosis of human placental trophoblast cells mediated by ER stress-induced ROS or UPR pathways.

Perfluorooctanoate acid (PFOA) is a highly persistent and widespread chemical in the environment. PFOA serum levels in pregnant women are positively associated with an increased risk of placenta-related disorders. However, the mechanism of PFOA cytotoxicity involved in placental cells and cellular responses such as ER stress remains poorly understood. In this study, we studied the cellular toxicity of PFOA with a focus on proliferation and apoptosis in a human placental trophoblast cell line. Cell viability, number, apoptosis, stress response, activation of the involved signaling pathways were assessed. Our results showed PFOA affected cell viability, proliferation and also resulted in apoptosis. Besides, both pro-proliferation and pro-apoptosis effects were attenuated by endoplasmic reticulum (ER) stress inhibitors. Further experiments demonstrated that two different signaling pathways were activated by PFOA-induced ER stress and involved in PFOA toxicity: the reactive oxygen species (ROS)-dependent ERK signaling triggered trophoblast proliferation, while the ATF4-dependent C/EBP homologous protein (CHOP) signaling was the trigger of apoptosis. We conclude that PFOA-induced ER stress is the trigger of proliferation and apoptosis of trophoblast via ROS or UPR signaling pathway, which leads to the altered balance critical to the normal development and function of the placenta.

Prognostic Value of a Novel Parameter in Patients with Infective Endocarditis.

Background: Infective endocarditis (IE) has a high rate of mortality and the prognosis of IE was poor. The purpose of this investigation was to explore the value of lactate dehydrogenase (LDH)/lymphocyte and compare it with LDH/lymphocyte percentage (L-LWR) in predicting the in-hospital mortality in IE patients. Methods: The investigation cohort contained 147 IE patients between January 2017 and December 2019. We retrospectively went over the medical records and selected admission indexes. Results: Compared with IE patients with adverse events, significantly higher levels of LDH/lymphocyte and significantly lower levels of L-LWR were discovered in IE patients without adverse events. After adjustments, L-LWR (odds ratio (OR): 4.558, 95% confidence interval (CI) 1.362-15.256, P = 0.014) still maintained its significant independence. In addition, L-LWR had the highest area under curve (AUC) (0.780, 0.704-0.844, P < 0.001) with good sensitivity (81.89%) and specificity (65.00%) when 34 was selected as the best cutoff value. Conclusions: L-LWR is a reliable, low-priced, easily applicable, and independent prognostic parameter for in-hospital death with good performance in patients with IE.

The association between systemic inflammatory response index and in-hospital mortality in patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) has a significant mortality, and early identification of high-risk patients and prediction of poor outcomes is of great significance. In recent years, increasing research has revealed the predictors associated with infective endocarditis prognosis. Systemic inflammatory response index (SIRI) is an important new indicator of inflammation. So far, there have been no reports on the relationship between SIRI and the prognosis of IE patients. HYPOTHESIS: The purpose of this study was to explore the value of SIRI in predicting in-hospital death for patients with infective endocarditis (IE), so as to provide reference for improving the prognosis of patients with IE. METHOD: A retrospective analysis was performed on the clinical data of patients with IE admitted to the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2019. SIRI was calculated according to the blood routine results of patients at admission; receiver operating characteristic curve was employed to determined the optimal cutoff value of SIRI. Patients were divided into groups (low SIRI group and high SIRI group; nonsurvivor group and survivor group) according to the levels of SIRI or their prognosis, and the general clinical features of the two groups were compared. Univariate and multivariate logistic regression analysis were performed to analyze the independent prognostic factors of in-hospital death in IE patients. RESULTS: A total of 147 IE patients meeting the diagnostic criteria were included, including 102 males (69.4%) and 45 females (30.6%). There was statistically significant difference in SIRI level between nonsurvivor group and survivor group (p < .05). After adjusting for the related factors, the risk of in-hospital death in the high SIRI was still a risk of in-hospital death with statistical significance (hazard ratio = 5.053, 95% confidence interval: 1.426-17.905, p = .012). CONCLUSIONS: Higher SIRI level is independently associated with the risk of in-hospital death in IE patients, and can be an independent predictor of poor outcome in IE patients.

Development and validation of a prediction model for malignant pulmonary nodules: A cohort study.

ABSTRACT: This study is to develop and validate a preoperative prediction model for malignancy of solitary pulmonary nodules. Data from 409 patients who underwent solitary pulmonary nodule resection at the First Affiliated Hospital of Nanjing Medical University, China between June 2018 and December 2020 were retrospectively collected. Then, the patients were nonrandomly split into a training cohort and a validation cohort. Clinical features, imaging parameters and laboratory data were then collected. Logistic regression analysis was used to develop a prediction model to identify variables significantly associated with malignant pulmonary nodules (MPNs) that were then included in the nomogram. We evaluated the discrimination and calibration ability of the nomogram by concordance index and calibration plot, respectively. MPNs were confirmed in 215 (52.6%) patients by a pathological examination. Multivariate logistic regression analysis identified 6 risk factors independently associated with MPN: gender (female, odds ratio [OR] = 2.487; 95% confidence interval [CI]: 1.313-4.711; P = .005), location of nodule (upper lobe of lung, OR = 1.126; 95%CI: 1.054-1.204; P < .001), density of nodule (pure ground glass, OR = 4.899; 95%CI: 2.572-9.716; P < .001; part-solid nodules, OR = 6.096; 95%CI: 3.153-14.186; P < .001), nodule size (OR = 1.193; 95%CI: 1.107-1.290; P < .001), GAGE7 (OR = 1.954; 95%CI: 1.054-3.624; P = .033), and GBU4-5 (OR = 2.576; 95%CI: 1.380-4.806; P = .003). The concordance index was 0.86 (95%CI: 0.83-0.91) and 0.88 (95%CI: 0.84-0.94) in the training and validation cohorts, respectively. The calibration curves showed good agreement between the predicted risk by the nomogram and real outcomes. We have developed and validated a preoperative prediction model for MPNs. The model could aid physicians in clinical treatment decision making.