Use of pressure muscle index to guide pressure support ventilation setting: a study protocol and statistical plan for a prospective randomised controlled proof-of-concept trial.

INTRODUCTION: Although pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support. By performing an end-inspiratory airway occlusion, the difference between the peak and plateau airway pressure, which is defined as pressure muscle index (PMI), can be easily measured on the ventilator screen. Previous studies have shown that PMI is accurate in detecting high and low inspiratory effort. No study has been conducted to investigate the use of PMI as an indicator for setting inspiratory pressure support. METHOD AND ANALYSIS: This is a study protocol for a prospective, single-centre, randomised controlled, pilot trial. Sixty participants undergoing pressure support ventilation will be randomly assigned in a 1:1 ratio to the control group or intervention group, with pressure support adjusted according to standard care or guided by the PMI strategy for 48 hours, respectively. The feasibility of the PMI-guided strategy will be evaluated. The primary endpoint is the proportion of inspiratory effort measurements within a well-accepted 'normal' range, which is predefined as oesophageal pressure-time product per minute between 50 and 200 cmH2O⋅s/min, for each patient during 48 hours of pressure support adjustment. ETHICS AND DISSEMINATION: The study protocol has been approved by Beijing Tiantan Hospital (KY2023-005-02). The data generated in the present study will be available from the corresponding author on reasonable request. The results of the trial will be submitted to international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05963737; ClinicalTrials.org.

The value of radiomics features of the spleen as surrogates for differentiating subtypes of common pediatric lymphomas.

Background: Lymphoma is a common malignant tumor in children. The pathologic subtyping of lymphoma is high complex, and the treatment options vary. The different pathologic subtypes of lymphomas have no significant differences on computed tomography (CT) images. As it is a hematologic disease, patients with lymphoma often show abnormalities in the spleen, and so the aim of this study was to construct a model for differentiating Burkitt lymphoma (BL) from lymphoblastic lymphoma through the extraction of radiomic features of the spleen from CT images. This could provide an efficient, noninvasive method that can differentiate the common pathological subtypes in patients with pediatric lymphoma. Methods: The clinical data and imaging data of 48 patients with lymphoblastic lymphoma and 61 patients with BL were retrospectively analyzed. The dataset was divided into a training set (n=76) and a test set (n=33) through complete randomization. Radiomics features of the spleen were separately extracted from CT images in the noncontrast enhanced, arterial, and venous phases. These phase-specific features were integrated to construct fusion models. Three classifiers, quadratic discriminant analysis (QDA), logistic regression (LR), and support vector machine (SVM), were employed to build the models. Results: The fusion model exhibited superior performance compared to individual models. There was no significant difference between the fusion models constructed by QDA and LR in either the training set or the test set. Among the four fusion models constructed with the SVM classifier, SVM_4 emerged as the best performing model. The area under the curve, sensitivity, specificity, and F1-score of the SVM_4 model were 0.967 [95% confidence interval (CI): 0.935-0.998], 0.86, 0.97, and 0.913 in the training set, respectively, and 0.754 (95% CI: 0.584-0.924), 0.611, 0.867, and 0.71 in the test set, respectively. Conclusions: The radiomics features of the spleen demonstrated the capability to distinguish between the two most common lymphoma subtypes in pediatric patients. This noninvasive approach holds promise for efficient and accurate discrimination.

Palladium nanocrystals regulates scleral extracellular matrix remodeling in myopic progression by modulating the hypoxia signaling pathway Nrf-2/Ho-1.

Myopia represents a widespread global public health concern influenced by a combination of environmental and genetic factors. The prevailing theory explaining myopia development revolves around scleral extracellular matrix (ECM) remodeling, characterized by diminished Type I collagen (Col-1) synthesis and increased degradation, resulting in scleral thinning and eye axis elongation. Existing studies underscore the pivotal role of scleral hypoxia in myopic scleral remodeling. This study investigates the peroxidase-like activity and catalytic performance of octahedral Palladium (Pd) nanocrystals, recognized as nanozymes with antioxidative properties. We explore their potential in reducing oxidative stress and alleviating hypoxia in human scleral fibroblasts (HSF) and examine the associated molecular mechanisms. Our results demonstrate the significant peroxidase-like activity of Pd nanocrystals. Furthermore, we observe a substantial reduction in oxidative stress in HSF under hypoxia, mitigating cellular damage. These effects are linked to alterations in Nrf-2/Ho-1 expression, a pathway associated with hypoxic stress. Importantly, our findings indicate that Pd nanocrystals contribute to attenuated scleral matrix remodeling in myopic guinea pigs, effectively slowing myopia progression. This supports the hypothesis that Pd nanocrystals regulate myopia development by controlling oxidative stress associated with hypoxia. Based on these results, we propose that Pd nanocrystals represent a novel and potential treatment avenue for myopia through the modulation of scleral matrix remodeling. This study introduces innovative ideas and directions for the treatment and prevention of myopia.

Distinguishing diffuse large B-cell lymphoma from Hodgkin's lymphoma in children using an enhanced computed tomography radiomics approach.

Background: Diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) are two completely different pathologic subtypes of lymphoma with distinctly different clinical presentations and treatment options. Thus, accurately differentiating between the two subtypes has important clinical implications. This study aimed to construct a radiomics model capable of distinguishing between DLBCL and HL based on enhanced computed tomography (CT) for the non-invasive diagnosis of lymphoma subtypes. Methods: The clinical and imaging data of 16 patients confirmed to have DLBCL (33 lymphomas), and 50 patients confirmed to have HL (106 lymphomas) were retrospectively analyzed. The patients were completely randomized into a training set (n=107, DLBLC׃HL ratio: 23׃84) and a test set (n=32, DLBCL׃HL ratio: 10׃22). After multiple down-sampling, 2,264 radiomics features were automatically extracted by the application software. Feature selection was performed in the training set using Spearman's rank correlation coefficients, maximum correlation minimum redundancy, and the least absolute shrinkage and selection operator algorithm in that order. The features after selection were used to build radiomics models by logistic regression (LR) and quadratic discriminant analysis (QDA). We evaluated the model ability using receiver operating characteristic (ROC) curves and the DeLong test. Moreover, clinical indicators, such as gender, age, clinical stage, and lactate dehydrogenase (LDH), were collected and analyzed by univariate and multivariate LR analyses. The radiomics characteristics with clinical indicators that had independent influences on predicting the pathological subtypes were used to establish a comprehensive classification model. Results: The analysis of the clinical data revealed that LDH can serve as a clinical indicator that has an independent influence on the prediction of HL and DLBCL. The results of the radiomics models were as follows: Radiomics_LR: area under the curve (AUC) =0.814 [95% confidence interval (CI): 0.628-0.999]; and Radiomics_QDA: AUC =0.841 (95% CI: 0.691-0.991). Following the inclusion of LDH as a clinical indicator in the analysis, the results of the comprehensive models were as follows: Radiomics + LDH_LR: AUC =0.768 (95% CI: 0.580-0.956); and Radiomics + LDH_QDA: AUC was 0.845 (95% CI: 0.695-0.996). Conclusions: The models based on radiomics and clinical features were able to effectively distinguish DLBCL from HL. The model with the best overall performance was the Radiomics_LR model.

Long term impact of Wenchuan earthquake on population mental and behavioral disorders in heavily-stricken areas: An ecological study based on big data.

BACKGROUND: This study aimed to explore and evaluate the development trends and differential changes in the prevalence of mental and behavioral disorders among the earthquake survivors in exposure groups (highly hard-hit areas) and control groups (general disaster areas) from 2015 to 2019, as well as to investigate the potential influencing factors. METHODS: Data was obtained from the Sichuan Health Information System and the Sichuan Health Yearbook, the prevalence of the exposure group and the control group were calculated, the difference between the two groups was evaluated using the prevalence rate ratio, and a fixed effect model was developed to investigate the potential influencing factors of the prevalence. RESULTS: The prevalence by gender and age in the exposure group was always greater than those in the control group (RR>1), although the disparity between the two proceeded to diminish with time. The urbanization rate (ß = 0.0448, P < 0.05) and disaster area levels (ß = 0.0104, P < 0.05) were risk factors for the prevalence of mental and behavioral disorders. LIMITATIONS: The study only collected data at the group level following the Wenchuan earthquake. Consequently, the findings are only applicable at the group level. Furthermore, diagnostic criteria for various types of mental and behavioral disorders diseases were not provided. CONCLUSIONS: The earthquake has a significant long-term impact on mental health. It is necessary to continuously monitor the mental health of Wenchuan earthquake survivors and take appropriate post-disaster intervention measures.

Predicting response of hepatoblastoma primary lesions to neoadjuvant chemotherapy through contrast-enhanced computed tomography radiomics.

OBJECTIVE: To investigate the clinical value of contrast-enhanced computed tomography (CECT) radiomics for predicting the response of primary lesions to neoadjuvant chemotherapy in hepatoblastoma. METHODS: Clinical and CECT imaging data were retrospectively collected from 116 children with hepatoblastoma who received neoadjuvant chemotherapy. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, they were randomly stratified into a training cohort and a test cohort in a 7:3 ratio. The clinical model was constructed using univariate and multivariate logistic regression, while the radiomics model was developed based on selected radiomics features employing the support vector machine algorithm. The combined clinical-radiomics model incorporated both clinical and radiomics features. RESULTS: The area under the curve (AUC) for the clinical, radiomics, and combined models was 0.704 (95% CI: 0.563-0.845), 0.830 (95% CI: 0.704-0.959), and 0.874 (95% CI: 0.768-0.981) in the training cohort, respectively. In the validation cohort, the combined model achieved the highest mean AUC of 0.830 (95% CI 0.616-0.999), with a sensitivity, specificity, accuracy, precision, and f1 score of 72.0%, 81.1%, 78.5%, 57.2%, and 63.5%, respectively. CONCLUSION: CECT radiomics has the potential to predict primary lesion response to neoadjuvant chemotherapy in hepatoblastoma.

Use of pressure muscle index to predict the contribution of patient's inspiratory effort during pressure support ventilation: a prospective physiological study.

Background: The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support. Methods: In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort. Results: A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort. Conclusion: Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Chest Computed Tomography Radiomics for Determining Macrolide Resistance-Associated Gene Mutation Status in Children with Mycoplasma pneumoniae Pneumonia: A Two-Center Study.

RATIONALE AND OBJECTIVES: The mutations in the 23S ribosomal RNA (rRNA) gene are associated with an increase in resistance to macrolides in children with Mycoplasma pneumoniae pneumonia (MPP). This study aimed to develop and validate a chest computed tomography (CT) radiomics model for determining macrolide resistance-associated gene mutation status in MPP. MATERIALS AND METHODS: A total of 258 MPP patients were retrospectively included from two institutions (training set: 194 patients from the first institution; external test set: 64 patients from the second). The 23S rRNA gene mutation status was tested by nasopharyngeal swab polymerase chain reaction. Radiomics features were extracted from chest CT images of pulmonary lesions segmented with semi-automatic delineation. Subsequently, radiomics feature reduction was applied to identify the most relevant features. Logistic regression and random forest algorithms were employed to establish the radiomics models, which were five-fold cross-validated in the training set and validated in the external test set. RESULTS: The radiomics feature selection resulted in eight features. After five-fold cross-validation in the training set, the mean areas under the receiver operating characteristic curve (AUCs) of the logistic regression and random forest models were 0.868 (95% confidence interval (CI): 0.813-0.923) and 0.941 (95% CI: 0.907-0.975), respectively. In the external test set, the corresponding AUCs were 0.855 (95% CI: 0.758-0.952) and 0.815 (95% CI: 0.705-0.925). CONCLUSION: Chest CT radiomics is a promising diagnostic tool for determining macrolide resistance gene mutation status in MPP. AVAILABILITY OF DATA AND MATERIAL: The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

Characterization of three lamp genes from largemouth bass (Micropterus salmoides): molecular cloning, expression patterns, and their transcriptional levels in response to fast and refeeding strategy.

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

Multiprotease improves amino acid release in vitro, energy, and nutrient utilization in broilers fed diets varying in crude protein levels.

Low crude protein (CP) diets can reduce nitrogen (N) excretion and costs by increasing N utilization efficiency. Exogenous proteases may further improve protein digestibility in low CP diets. This study first evaluated in vitro the efficacy of a multiprotease on amino acid (AA) release from feedstuffs and broiler feed. Later, a broiler study evaluated the effect of feeding corn-soybean meal diets containing 3 CP levels (17, 19, and 21% CP) with supplementation on top of 0 or 2,400 U/kg multiprotease on chicken growth performance, total tract CP, and ileal AA digestibilities, and energy utilization. Ross 708 male chickens were placed in 42 cages and assigned to 6 treatments resulting from a 3 × 2 factorial arrangement. Three isocaloric basal diets were formulated to reduce CP, but all diets maintained digestible Lys:CP in 5.47% and the same ideal protein profile. Data were analyzed in a completely randomized design. On average, the multiprotease increased (P < 0.05) in vitro free AA release by 27.81% in most feedstuffs evaluated compared to the control. For broiler feed, 1,200 U/g multiprotease addition improved (P < 0.001) in vitro free AA release by 18.90%. This multiprotease showed interaction effects (P < 0.05) on chicken FCR, energy, and CP digestibility. As expected, BW at 24 d, BW gain, and FCR (8-24 d) worsened (P < 0.001) as dietary CP reduced from 21 to 17%, and multiprotease addition did not improve (P > 0.05) these parameters. BW gain decreased by 12.9% when N intake was reduced from 49.32 to 38.49 g/bird. Multiprotease supplementation improved (P < 0.01) AMEn by 71 kcal/kg, CP digestibility from 59.45 to 63.51%, ileal AA digestibility, and DM digestibility from 67.08 to 73.49%, but only in the 21% CP diet. No differences in ileal AA digestibility due to CP level (P > 0.05) were detected, except for Cys digestibility (P < 0.01). In conclusion, low CP diets reduced growth performance and improved N utilization but negatively affected energy utilization efficiency. Exogenous multiprotease supplementation improved AME, AMEn, protein, ileal AA, and DM digestibility in the 21% CP diet without significantly affecting growth performance.

Corrigendum: Study on the pathogenesis of MiR-6324 regulating diarrheal irritable bowel syndrome and bioinformatics analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1044330.].

Tanshinol inhibits trophoblast cell migration and invasion by regulating Gadd45a in preeclampsia.

OBJECTIVE: Tanshinol is an active constituent of Salvia miltiorrhiza that possesses anti-inflammatory, antioxidant, and antibacterial activities. Therefore, this study attempted to detect whether it has a role in the treatment of preeclampsia (PE). METHODS: In this study, we explored the effect of tanshinol on the development of PE at the cellular level. The effect of tanshinol on cell proliferation was measured by colony formation and EdU assays. The migration, invasion, and in vitro angiogenesis of HTR-8/SVneo cells were detected by wound-healing, transwell, and tube formation assays, respectively. In addition, a PE cell model was established by overexpression of Gadd45a, and this cell model was assessed with the optimal concentration of tanshinol. RESULTS: The results show that tanshinol enhanced proliferation, migration, invasion, and tube formation of HTR-8/SVneo cells in vitro. Furthermore, the reduction in proliferation, migration, invasion, and tube formation of cells by Gadd45a overexpression was partially reversed by tanshinol treatment. Tanshinol also inhibited the apoptosis of HTR-8/SVneo cells transfected with Gadd45a. CONCLUSIONS: In summary, tanshinol promoted proliferation, migration, invasion, and tube formation and inhibited the apoptosis of HTR-8/SVneo cells. It may be a novel therapeutic compound to attenuate the development of PE.

Traditional Chinese medicine has maintained the health of people in Asia for thousands of years and is increasingly used worldwide. Tanshinol has been found to be useful in the treatment and prevention of many diseases. Through experiments, we found that tanshinol is a novel therapeutic compound that promotes the proliferation, migration, invasion and tubular formation of HTR-8/SVneo cells. In addition, tanshinol also inhibited the apoptosis rate of preeclampsia cell models. Follow-up experiments will further validate the results of this study.

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study.

BACKGROUND: Assessment of the patient's respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation. METHODS: In this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus-time product per minute (PTPmus/min) were used as the reference standard for the patient's effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min-1, respectively. RESULTS: A total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83-0.96), specificity (0.74-0.88), and positive (0.80-0.91) and negative predictive values (0.78-0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93-0.95). A high sensitivity (0.80-1.00) and negative predictive value (0.97-1.00) were found with a low positive predictive value (0.23-0.64). CONCLUSIONS: By performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Perceived knowledge, attitudes and practices regarding the medical consortium among medical staff in Sichuan, China: a cross-sectional survey.

BACKGROUND: In China, fragmented and inefficient health care systems are common while quality resources are limited. To promote an organized, efficient system, the government launched a medical consortium policy to vertically integrate health care through the collaboration of different levels of medical care. Logically, medical staff's knowledge, attitudes and practices (KAP) regarding the consortium are critical for its development. The objective of this study was to explore the KAP regarding the medical consortium among medical staff in a medical consortium in Sichuan Province, China. METHODS: A cross-sectional survey was conducted. In total, 690 medical staff members in 3 cities of Sichuan Province, China, were interviewed from November 2018 to December 2018. The questionnaire consisted of 18 items, including 4 items related to perceived knowledge, 4 items related to attitudes and 2 items related to practices, and was rated on a 5-point Likert scale (one = strongly disagree/do not know, five = strongly agree/know). RESULTS: The effective response sample was 640 copies of the questionnaire, and most medical staff members (92.50%) knew about the cooperation with other hospitals in the medical consortium. Medical staff scored differently on each item in the questionnaire, with the highest score being the item 'agreeing with the ward rounds and clinical teaching and training organized by the leading hospital' (4.54 ± 0.76), and the lowest score being the item 'frequency in participating in ward rounds and clinical teaching organized by the leading hospital' (2.83 ± 1.36). In addition, the effect of demographic characteristics on KAP was evaluated by stepwise multiple regression analysis, and a significant positive correlation was found between all the studied variables by Spearman's correlation (p < 0.05). CONCLUSIONS: This study showed that the attitudes toward and knowledge of the medical consortium significantly contribute to practices, satisfaction with the support work performed by the leading hospital and agreement of improvement after joining the medical consortium. Thus, to improve medical staff's KAP and satisfaction, publicity and educational programs in medical consortia are necessary, and the leading hospital should attach importance to the informatization construction and demand of different medical staff members. CLINICAL TRIAL REGISTRATION: There are no clinical trials in this study.

Ecliptasaponin A attenuates renal fibrosis by regulating the extracellular matrix of renal tubular cells.

Renal fibrosis is the most common manifestation of end-stage renal disease (ESRD), including diabetic kidney disease (DKD), but there is no effective treatment in renal fibrosis. Natural products are a rich source of clinical drug research and have been used in the clinical research of various diseases. In this study, we searched for traditional Chinese medicine monomers that attenuate fibrosis and assessed their effect on the fibrosis marker connective tissue growth factor (CTGF) in cells which we found ecliptasaponin A. Subsequently, we evaluated the effect of ecliptasaponin A on renal fibrosis in the classic renal fibrosis unilateral ureteral obstruction (UUO) mouse model and found that ecliptasaponin A could reduce the renal collagen fiber deposition and renal extracellular matrix (ECM) protein expression in UUO mice. In vitro, ecliptasaponin A can inhibit ECM protein expression in human kidney-2 (HK-2) cells induced by transforming growth factor-beta1 (TGFß1). To further clarify the mechanism of ecliptasaponin A in attenuating renal fibrosis, we performed transcriptome sequencing of HK-2 cells treated with TGFß1 and ecliptasaponin A. The functions and pathways were mainly enriched in the extracellular matrix and TGFß signalling pathway. Matrix metalloproteinase 10 (MMP10) and matrix metalloproteinase 13 (MMP13) are the main differentially expressed genes in extracellular matrix regulation. Then, we measured MMP10 and MMP13 in the cells and found that ecliptasaponin A had a significant inhibitory effect on MMP13 expression but not on MMP10 expression. Furthermore, we overexpressed MMP13 in HK-2 cells treated with TGFß1 and found that MMP13 promoted HK-2 cell injury. Our findings suggest that ecliptasaponin A can attenuate renal fibrosis, which may provide a new method for treating renal fibrosis clinically.

Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

Development of a Prediction Score for Evaluation of Extubation Readiness in Neurosurgical Patients with Mechanical Ventilation.

BACKGROUND: There is no widely accepted consensus on the weaning and extubating protocols for neurosurgical patients, leading to heterogeneity in clinical practices and high rates of delayed extubation and extubation failure-related health complications. METHODS: In this single-center prospective observational diagnostic study, mechanically ventilated neurosurgical patients with extubation attempts were consecutively enrolled for 1 yr. Responsive physicians were surveyed for the reasons for delayed extubation and developed the Swallowing, Tongue protrusion, Airway protection reflected by spontaneous and suctioning cough, and Glasgow Coma Scale Evaluation (STAGE) score to predict the extubation success for neurosurgical patients already meeting other general extubation criteria. RESULTS: A total of 3,171 patients were screened consecutively, and 226 patients were enrolled in this study. The rates of delayed extubation and extubation failure were 25% (57 of 226) and 19% (43 of 226), respectively. The most common reasons for the extubation delay were weak airway-protecting function and poor consciousness. The area under the receiver operating characteristics curve of the total STAGE score associated with extubation success was 0.72 (95% CI, 0.64 to 0.79). Guided by the highest Youden index, the cutoff point for the STAGE score was set at 6 with 59% (95% CI, 51 to 66%) sensitivity, 74% (95% CI, 59 to 86%) specificity, 90% (95% CI, 84 to 95%) positive predictive value, and 30% (95% CI, 21 to 39%) negative predictive value. At STAGE scores of 9 or higher, the model exhibited a 100% (95% CI, 90 to 100%) specificity and 100% (95% CI, 72 to 100%) positive predictive value for predicting extubation success. CONCLUSIONS: After a survey of the reasons for delayed extubation, the STAGE scoring system was developed to better predict the extubation success rate. This scoring system has promising potential in predicting extubation readiness and may help clinicians avoid delayed extubation and failed extubation-related health complications in neurosurgical patients.

CERS6-derived ceramides aggravate kidney fibrosis by inhibiting PINK1-mediated mitophagy in diabetic kidney disease.

During diabetic kidney disease (DKD), ectopic ceramide (CER) accumulation in renal tubular epithelial cells (RTECs) is associated with interstitial fibrosis and albuminuria. As RTECs are primarily responsible for renal energy metabolism, their function is intimately linked to mitochondrial quality control. The role of CER synthesis in the progression of diabetic renal fibrosis has not been thoroughly investigated. In this study, we observed a significant upregulation of ceramide synthase 6 (Cers6) expression in the renal cortex of db/db mice, coinciding with increased production of CER (d18:1/14:0) and CER (d18:1/16:0) by Cer6. Concurrently, the number of damaged mitochondria in RTECs rose. Cers6 deficiency reduced the abnormal accumulation of CER (d18:1/14:0) and CER (d18:1/16:0) in the kidney cortex, restoring the PTEN-induced kinase 1 (PINK1)-mediated mitophagy in RTECs, and resulting in a decrease in damaged mitochondria and attenuation of interstitial fibrosis in DKD. Automated docking analysis suggested that both CER (d18:1/14:0) and CER (d18:1/16:0) could bind to the PINK1 protein. Furthermore, inhibiting PINK1 expression in CERS6 knockdown HK-2 cells diminished the therapeutic effect of CERS6 deficiency on DKD. In summary, CERS6-derived CER (d18:1/14:0) and CER (d18:1/16:0) inhibit PINK1-regulated mitophagy by possibly binding to the PINK1 protein, thereby exacerbating the progression of renal interstitial fibrosis in DKD.NEW & NOTEWORTHY This article addresses the roles of ceramide synthase 6 (CERS6) and CERS6-derived ceramides in renal tubular epithelial cells of diabetic kidney disease (DKD) associated interstitial fibrosis. Results from knockdown of CERS6 adjusted the ceramide pool in kidney cortex and markedly protected from diabetic-induced kidney fibrosis in vivo and in vitro. Mechanically, CERS6-derived ceramides might interact with PINK1 to inhibit PINK1/Parkin-mediated mitophagy and aggravate renal interstitial fibrosis in DKD.

Intracardiac thrombosis after congenital heart disease surgeries in neonates: a report of two cases.

BACKGROUND: Intracardiac thrombosis (ICT) is a rare complication after the cardiopulmonary surgery for interrupted aortic arch (IAA) or total anomalous pulmonary venous connection (TAPVC) without previous records. There are still no general guidelines regarding as the mechanism or management of postoperative ICT in neonates and younger infants. CASE PRESENTATION: We reported the conservative and surgical therapies in two neonates with intra-ventricular and intra-atrial thrombosis after the anatomical repair for IAA and TAPVC, respectively. There were no risk factors for ICT in both patients, except for the use of blood product and prothrombin complex concentrate. The surgery was indicated after TAPVC correction due to the worsening respiratory status and rapidly decreased mixed venous saturation. Anticoagulation combined with antiplatelet therapies was adopted in another patient. These two were both finally recovered, and three-month, six-month, and one-year follow-up echocardiography revealed no abnormality. CONCLUSIONS: ICT is uncommon in pediatric population after the surgery for congenital heart disease. Single ventricle palliation, heart transplantation, longer central line use, post-extracorporeal membrane oxygenation, and massive blood product use are major risk factors for postcardiotomy thrombosis. The causes of postoperative ICT are multifactorial, and the immaturity of thrombolytic and fibrinolytic system in neonates may serve as a prothrombotic factor. However, no consensus reached regarding as the therapies for postoperative ICT, and the large-scale prospective cohort study or randomized clinical trial is needed.