Pharmacological inhibition of the ACE/Ang-2/AT1 axis alleviates mechanical ventilation-induced pulmonary fibrosis.

Mechanical ventilation (MV) is an essential therapy for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. However, it can also induce mechanical ventilation-induced pulmonary fibrosis (MVPF) and the underlying mechanism remains unknown. Based on a mouse model of MVPF, the present study aimed to explore the role of the angiotensin-converting enzyme/angiotensin II/angiotensin type 1 receptor (ACE/Ang-2/AT1R) axis in the process of MVPF. In addition, recombinant angiotensin-converting enzyme 2(rACE2), AT1R inhibitor valsartan, AGTR1-directed shRNA and ACE inhibitor perindopril were applied to verify the effect of inhibiting ACE/Ang-2/AT1R axis in the treatment of MVPF. Our study found MV induced an inflammatory reaction and collagen deposition in mouse lung tissue accompanied by the activation of ACE in lung tissue, increased concentration of Ang-2 in bronchoalveolar lavage fluid (BALF), and upregulation of AT1R in alveolar epithelial cells. The process of pulmonary fibrosis could be alleviated by the application of the ACE inhibitor perindopril, ATIR inhibitor valsartan and AGTR1-directed shRNA. Meanwhile, rACE2 could also alleviate MVPF through the degradation of Ang-2. Our finding indicated the ACE/Ang-2/AT1R axis played an essential role in the pathogenesis of MVPF. Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF.

Worldwide productivity and research trend of publications concerning extracellular vesicles role in fibrosis: A bibliometric study from 2013 to 2022.

Background: Fibrosis is a heavy burden on the global healthcare system. Recently, an increasing number of studies have demonstrated that Extracellular vesicles play an important role in intercellular communication under both physiological and pathological conditions. This study aimed to explore the role of extracellular vesicles' in fibrosis using bibliometric methods. Methods: Original articles and reviews related to extracellular vesicles and fibrosis were obtained from the Web of Science Core Collection database on November 9, 2022. VOSviewer was used to obtain general information, including co-institution, co-authorship, and co-occurrence visualization maps. The CiteSpace software was used to analyze citation bursts of keywords and references, a timeline view of the top clusters of keywords and cited articles, and the dual map. R package "bibliometrix" was used to analyze annual production, citation per year, collaboration network between countries/regions, thematic evolution map, and historiography network. Results: In total, 3376 articles related to extracellular vesicles and fibrosis published from 2013 to 2022 were included in this study, with China and the United States being the top contributors. Shanghai Jiao Tong University has the highest number of publications. The main collaborators were Giovanni Camussi, Stefania Bruno, Marta Tepparo, and Cristina Grange. Journals related to molecular, biology, genetics, health, immunology, and medicine tended to publish literature on extracellular vesicles and fibrosis. "Recovery," "heterogeneity," "degradation," "inflammation," and "mesenchymal stem cells" are the keywords in this research field. Literature on extracellular vesicles and fibrosis associated with several diseases, including "kidney disease," "rheumatoid arthritis," and "skin regeneration" may be the latest hot research field. Conclusions: This study provides a comprehensive perspective on extracellular vesicles and fibrosis through a bibliometric analysis of articles published between 2013 and 2022. We identified the most influential countries, institutions, authors, and journals. We provide information on recent research frontiers and trends for scholars interested in the field of extracellular vesicles and fibrosis. Their role in biological processes has great potential to initiate a new upsurge in future research.

Green preparation of antibacterial shape memory foam based on bamboo cellulose nanofibril and waterborne polyurethane for adaptive relief of plantar pressure.

This study developed an aqueous solution blending and freeze-drying method to prepare an antibacterial shape memory foam (WPPU/CNF) based on waterborne PHMG-polyurethane and cellulose nanofibers derived from bamboo in response to the increasing demand for environmentally friendly, energy conserving, and multifunctional foams. The obtained WPPU/CNF composite foam has a highly porous network structure with well-dispersed CNFs forming hydrogen bonds with the WPPU matrix, which results in a stable and rigid cell skeleton with enhanced mechanical properties (80 KPa) and anti-abrasion ability. The presence of guanidine in the polyurethane chain endowed the WPPU/CNF composite foam with an instinctive and sustained antibacterial ability against Escherichia coli and Staphylococcus aureus. The WPPU/CNF composite foam exhibited a water-sensitive shape memory function in a cyclic shape memory program because of the chemomechanical adaptability of the hydrogen-bonded network of CNFs in the elastomer matrix. The shape-fixation ratio for local compression reached 95 %, and the shape-recovery rate reached 100 %. This allows the WPPU/CNF pad prototype to reversibly adjust the undulation height to adapt to plantar ulcers, which can reduce the local plantar pressure by 60 %. This study provides an environmentally friendly strategy for cellulose-based composite fabrication and enriches the design and application of intelligent foam devices.

METFORMIN MITIGATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY PROMOTING AMPK ACTIVATION AND INHIBITING HIF-1α-INDUCED AEROBIC GLYCOLYSIS.

ABSTRACT: Recent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)-induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. Cellular experiments demonstrated that lipopolysaccharide increased fibroblast activation through AMPK inactivation, HIF-1α induction, alongside an augmentation of aerobic glycolysis. By contrast, the effects were reversed by AMPK activation or HIF-1α inhibition. In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effects in vivo . Our research implies that targeting AMPK activation and HIF-1α-induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF.

Spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a Chinese child: A case report.

RATIONALE: Mutations in the gene encoding type VI collagen cause Bethlem myopathy (MIM 158810) and Ullrich congenital muscular dystrophy (MIM 254090); 2 diseases previously recognized as completely independent, and have been increasingly recognized. However, collagen-related myopathy caused by intron variation in the COL6 gene is rarely reported in China. Ullrich congenital muscular dystrophy is an autosomal recessive disorder that leads to severe muscle weakness with early onset. Thus, children may never walk independently, with proximal joint contractures and significant hyperelastic distal joints, and have early respiratory failure. Therefore, timely diagnosis and treatment are important. We report a spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a pediatric patient. PATIENT CONCERNS: A boy aged 4 years was unable to walk independently, could sit alone for a short time, and his motor development was delayed and had regressed after 1 year of age. He had a high palatal arch and a through palm with localized transverse lines running laterally from the palm. Electromyography showed an impaired neurogenic source, and whole-exon gene sequencing revealed a spontaneous heterozygous mutation in the COL6A2 gene (c.955-2A>G), which was determined to be a pathogenic mutation according to the American Guidelines of the College of Medical Genetics. DIAGNOSES: This child has a delayed motor development, high osprey arch and a through palm with localized transverse lines running laterally from the palm, and regression of motor development after the age of 1 year. Whole exon examination showed spontaneous mutation of the COL6A2 gene; thus, the child was diagnosed with UCMD type 1. INTERVENTIONS: At present, there is no special treatment for this disease, and treatment is mainly symptomatic and supportive. The child underwent home massage, rehabilitation training, oral folic acid tablets, vitamins and coenzyme Q10. OUTCOMES: During the subsequent follow-up period, the patient can now sit alone for a short period of time. LESSONS: We report a case of spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a pediatric patient, expanding the phenotypic spectrum of the disease and enriching the human gene pool.

Citrin deficiency due to SLC25A13 exon deletion in a Chinese infant: A case report.

INTRODUCTION: Citrin is a calcium-bound aspartate-glutamate carrier protein encoded by the gene SLC25A13, mutations of which can cause citrin deficiency, an autosomal recessive disorder. The manifestations of citrin deficiency include neonatal intrahepatic choledeposits caused by citrin deficiency (NICCD: OMIM#605814), intermediate growth disorders and dyslipidemia caused by citrin deficiency, and citrullinemia type II (OMIM#603471) in adults. NICCD is a classical metabolic disorder that causes cholestasis in newborns. PATIENT CONCERN AND CLINICAL FINDINGS: Here, we present the case of a 2-month-old male patient treated in our hospital on March 20, 2023, due to "postnatal skin xanthochromia and transaminases higher than normal values". Since birth, the child's skin had yellowed all over the body, and his condition did not improve after multiple medical treatments. DIAGNOSIS/INTERVENTION/OUTCOMES: The child underwent full exome gene testing at the age of 2 months and 13 days, and the results indicated heterozygous deletion of exon 3 of the SLC25A13 gene, while genetic testing of the parents revealed no gene mutations. The variant was preliminarily judged as being pathogenic according to the ACMG guidelines, and the patient was diagnosed with "citrin deficiency". Skin yellowing eventually subsided, and liver function returned to normal without special treatment. CONCLUSIONS: Here, we report a rare case of citrin deficiency caused by a heterozygous deletion of the SLC25A13 gene. This case increases the clinical phenotypic profile of NICCD, suggesting that clinicians must be vigilant regarding such genetic metabolic diseases in the clinic for early diagnosis and treatment. NICCD should always be considered in the differential diagnosis of neonatal cholestasis.

Large-range lithography nano-alignment without phase unwrapping by a dual-frequency moiré fringe heterodyne.

Moiré fringe is an effective approach to realize nano-alignment. However, affected by short periodicity and phase unwrapping, moiré fringe technology has small alignment ranges and redundant algorithms, making it difficult to meet practical application requirements. To solve the problem, we propose a large-range lithography nano-alignment method without phase unwrapping by a dual-frequency moiré fringe heterodyne. This method obtains four sets of moiré fringes from the main and differential alignment marks and then calculates the misalignment information using the heterodyne method. In this approach, both large alignment range and high alignment accuracy are achieved while avoiding the phase unwrapping process. The experimental results verified the rationality and feasibility of the proposed method.

[Research on the mechanism of mechanical ventilation induced endoplasmic reticulum stress promoting mechanical ventilation-induced pulmonary fibrosis].

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/ß-actin: 1.40±0.02 vs. 1, BIP/ß-actin: 2.79±0.07 vs. 1, PDI/ß-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/ß-actin: 0.53±0.03 vs. 1.40±0.02, BIP/ß-actin: 1.73±0.15 vs. 2.79±0.07, PDI/ß-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad+/AT1R+ and E-cad+/BIP+ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS: MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.

Efficient Fourier single-pixel imaging based on weighted sorting.

Fourier single-pixel imaging (FSI) has attracted increased attention in recent years with the advantages of a wide spectrum range and low cost. FSI reconstructs a scene by directly measuring the Fourier coefficients with a single-pixel detector. However, the existing sampling method is difficult to balance the noise suppression and image details within a limited number of measurements. Here we propose a new sampling strategy for FSI to solve this problem. Both the generality of the spectral distribution of natural images in the Fourier domain and the uniqueness of the spectral distribution of the target images in the Fourier domain are considered in the proposed method. These two distributions are summed with certain weights to determine the importance of the Fourier coefficients. Then these coefficients are sampled in order of decreasing importance. Both the simulations and experiments demonstrate that the proposed method can capture more key Fourier coefficients and retain more details with lower noise. The proposed method provides an efficient way for Fourier coefficient acquisition.

A deep learning model for predicting COVID-19 ARDS in critically ill patients.

Background: The coronavirus disease 2019 (COVID-19) is an acute infectious pneumonia caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection previously unknown to humans. However, predictive studies of acute respiratory distress syndrome (ARDS) in patients with COVID-19 are limited. In this study, we attempted to establish predictive models to predict ARDS caused by COVID-19 via a thorough analysis of patients' clinical data and CT images. Method: The data of included patients were retrospectively collected from the intensive care unit in our hospital from April 2022 to June 2022. The primary outcome was the development of ARDS after ICU admission. We first established two individual predictive models based on extreme gradient boosting (XGBoost) and convolutional neural network (CNN), respectively; then, an integrated model was developed by combining the two individual models. The performance of all the predictive models was evaluated using the area under receiver operating characteristic curve (AUC), confusion matrix, and calibration plot. Results: A total of 103 critically ill COVID-19 patients were included in this research, of which 23 patients (22.3%) developed ARDS after admission; five predictive variables were selected and further used to establish the machine learning models, and the XGBoost model yielded the most accurate predictions with the highest AUC (0.94, 95% CI: 0.91-0.96). The AUC of the CT-based convolutional neural network predictive model and the integrated model was 0.96 (95% CI: 0.93-0.98) and 0.97 (95% CI: 0.95-0.99), respectively. Conclusion: An integrated deep learning model could be used to predict COVID-19 ARDS in critically ill patients.

Fibrotic extracellular vesicles contribute to mechanical ventilation-induced pulmonary fibrosis development by activating lung fibroblasts via JNK signalling pathway: an experimental study.

Recent research has revealed that mechanical ventilation (MV) could initiate ventilator-induced lung injury along with the initiation of the process of pulmonary fibrosis (PF), leading to MV-induced PF (MVPF). However, the underlying mechanism remains unclear. This study aimed to explore the role of MV-induced extracellular vesicles (MV-EVs) and the c-Jun N-terminal kinase (JNK) signalling pathway in the pathogenesis of MVPF in vivo and in vitro. The process of MV is accompanied by the secretion of MV-EVs, which could induce lung fibroblast activation. Furthermore, single-cell RNA-sequencing analysis revealed that the JNK pathway in lung fibroblasts was activated after MV initiation. Inhibiting the JNK pathway could both restrain MV-EV-induced lung fibroblast activation in vitro or reduce the severity of MVPF in vivo. In conclusion, this study demonstrated that MV-EVs contribute to MVPF progression by activating lung fibroblasts via the JNK signalling pathway and that inhibiting the secretion of EV and the activation of the JNK signalling pathway is a promising strategy for treating MVPF.

Eosinophilic granuloma of the clavicle in an 11-year-old Chinese girl: A case report.

RATIONALE: Eosinophilic granuloma (EG) - the most common form of Langerhans cell histiocytosis - occurs rarely, and manifestations with only rib and clavicle involvement are extremely rare. EG symptoms often include pain, swelling, and soft tissue mass. The clinical diagnosis of bone EG is complex, and the differential diagnosis includes Ewing sarcoma, tuberculosis, multiple myeloma, lymphoma, primary bone malignancy, and other osteolytic lesions. PATIENTS CONCERN: The patient was an 11-year-old female who found a subcutaneous mass at the junction of the right clavicle and sternum 2 days before presenting at the clinic without apparent triggers. Initially, we considered a subcutaneous cyst or inflammatory mass. Color ultrasound and computed tomography examination revealed osteomyelitis. Finally, the patient was diagnosed with EG after a pathological tissue biopsy, and the child recovered after surgery and anti-infective treatment. DIAGNOSIS: The patient underwent surgery to remove the tumor at a specialist hospital and was diagnosed with EG by pathological examination. INTERVENTION: The patient went to a specialist hospital for surgery to remove the mass and underwent anti-infective treatment. OUTCOMES: The patient recovered after surgical resection and antibiotic treatment. LESSONS: In this report, we emphasize that the clinical presentation of EG in children is not specific. Furthermore, examining age, history, presence of symptoms, and the number of sites is essential to make a correct diagnosis, and a histological examination is necessary to confirm the diagnosis.

High-order spatial phase shift method realizes modulation analysis through a single-frame image.

For the modulation-based structured illumination microscopy system, how to obtain modulation distribution with an image has been a research hotspot. However, the existing frequency-domain single-frame algorithms (mainly including the Fourier transform method, wavelet method, etc.) suffer from different degrees of analytical error due to the loss of high-frequency information. Recently, a modulation-based spatial area phase-shifting method was proposed; it can obtain higher precision by retaining high-frequency information effectively. But for discontinuous (such as step) topography, it would be somewhat smooth. To solve the problem, we propose a high-order spatial phase shift algorithm that realizes robust modulation analysis of a discontinuous surface with a single-frame image. At the same time, this technique proposes a residual optimization strategy, so that it can be applied to the measurement of complex topography, especially discontinuous topography. Simulation and experimental results demonstrate that the proposed method can provide higher-precision measurement.

Study on the application effect of the family doctor contract service mode of 'basic package+personalised package' in elderly hypertension management in Chengdu, China: a retrospective observational study.

OBJECTIVES: We conducted this study to assess the application effect of the family doctor contract service mode of 'basic package+personalised package' in the management of hypertension patients. DESIGN: Observational study. SETTING: The study was conducted at a community health centre in Southwest China. Data were collected from 1 January 2018 to 31 December 2020. PARTICIPANTS: From 1 January 2018 to 31 December 2020, hypertensive patients (age ≥65 years) who participated in the contract services of family doctors at a community health service centre in Chengdu, Southwest China, were selected as the study subjects. MAIN OUTCOME MEASURES: The primary outcomes included mean blood pressure (systolic, diastolic) and the rate of blood pressure control, secondary outcomes included the level of cardiovascular disease risk and self-management ability. Assessments of baseline and 6 months after signing up were conducted on all outcomes. The major statistical analysis methods included two independent sample t-tests, paired t-tests, Pearson's χ2 test, McNemar's test, two independent sample Mann-Whitney U tests and paired sample marginal homogeneity tests. RESULTS: Of the 10 970 patients screened for eligibility, 968 (8.8%) were separated into an observation group (receiving 'basic package+personalised package (hypertension)' service) (n=403) and a control group (receiving 'basic package' service) (n=565) according to the type of service package they received. In comparison to the control group, the observation group had lower mean systolic blood pressure (p=0.023), higher blood pressure control rate (p<0.001), lower cardiovascular disease risk level (p<0.001) and higher self-management ability level (p<0.001) at 6 months after signing up. The mean diastolic blood pressure of the two groups was not significantly different (p=0.735). CONCLUSIONS: The family doctor contract service model of 'basic package+personalised package (hypertension)' has a good application effect in the management of elderly hypertension, which can improve the average blood pressure, the rate of blood pressure control, the level of cardiovascular disease risk and self-management ability of the elderly with hypertension.

Thyroid hormone resistance resulting from a novel mutation in the THRB gene in a Chinese child: A case report.

INTRODUCTION: Thyroid hormone resistance (RTH) (mim # 188570) is a rare autosomal dominant genetic disorder characterized by reduced thyroid hormone response in target tissues. The clinical manifestations of RTH vary from no symptoms to symptoms of thyroid hormone deficiency to symptoms of thyroid hormone excess. PATIENT CONCERN AND CLINICAL FINDINGS: A 24-month-old girl presented with growth retardation, tachycardia, and persistently elevated thyroid hormones despite antithyroid treatment. DIAGNOSIS/INTERVENTION/OUTCOMES: The patient was diagnosed with RTH, after whole exon gene sequencing, found a de novo missense mutation (c.1375T > G,p.Phe459Val) in a novel locus of the thyroid hormone receptor beta gene. She had only mild growth retardation, so the decision was made to monitor her development without intervention. At her last follow-up at 5 years and 8 months of age, she continued to show growth retardation (-2 standard deviation below age-appropriate levels), in addition to delayed language development. Her comprehension ability and heart rate have remained normal. CONCLUSIONS: We report a mild case of RTH caused by a novel thyroid hormone receptor beta gene mutation. RTH should be considered in the differential diagnosis of abnormal serum thyroxine levels during neonatal screening.

[Progress in Application of Hyaluronic Acid-based Hydrogel on Surface of Medical Catheters].

Hyaluronic acid (HA) has favorable physicochemical properties and superior biological activities, which is an ideal biomaterial for preparing hydrogel coating. After physically or chemically modifying, HA-based hydrogel coating has been gradually applied to functional modification for medical catheters surface, such as hydrophilic lubricating coating, anti-inflammatory coating, biomedical antifouling coating and blood compatibility improved coating. However, there are still intractable problems in the coating technology of HA hydrogel which is applied to the surface of medical catheters, especially in adhesion, stability and element proportion of HA coating. Finally, the related influencing factors and improvement suggestions are analyzed in this study.

Non-coding RNA alterations in extracellular vesicles from bronchoalveolar lavage fluid contribute to mechanical ventilation-induced pulmonary fibrosis.

Objective: For respiratory failure patients, mechanical ventilation (MV) is a life-saving therapy to maintain respiratory function. However, MV could also cause damage to pulmonary structures, result in ventilator-induced lung injury (VILI) and eventually progress to mechanical ventilation-induced pulmonary fibrosis (MVPF). Mechanically ventilated patients with MVPF are closely related to increased mortality and poor quality of life in long-term survival. Thus, a thorough understanding of the involved mechanism is necessary. Methods: We used next-generation sequencing to identify differentially expressed non-coding RNAs (ncRNAs) in BALF EVs which were isolated from Sham and MV mice. Bioinformatics analysis was conducted to identify the engaged ncRNAs and related signaling pathways in the process of MVPF. Results: We found 1801 messenger RNAs (mRNA), 53 micro RNAs (miRNA), 273 circular RNAs (circRNA) and 552 long non-coding RNAs (lncRNA) in mice BALF EVs of two groups, which showed significant differential expression. TargetScan predicted that 53 differentially expressed miRNAs targeted 3105 mRNAs. MiRanda revealed that 273 differentially expressed circRNAs were associated with 241 mRNAs while 552 differentially expressed lncRNAs were predicated to target 20528 mRNAs. GO, KEGG pathway analysis and KOG classification showed that these differentially expressed ncRNA-targeted mRNAs were enriched in fibrosis related signaling pathways and biological processes. By taking the intersection of miRNAs target genes, circRNAs target genes and lncRNAs target genes, we found 24 common key genes and 6 downregulated genes were confirmed by qRT-PCR. Conclusions: Changes in BALF-EV ncRNAs may contribute to MVPF. Identification of key target genes involved in the pathogenesis of MVPF could lead to interventions that slow or reverse fibrosis progression.

Integrin ß3 Mediates Sepsis and Mechanical Ventilation-Associated Pulmonary Fibrosis Through Glycometabolic Reprogramming.

Mechanical ventilation (MV) has become a clinical first-line treatment option for patients with respiratory failure. However, it was unclear whether MV further aggravates the process of sepsis-associated pulmonary fibrosis and eventually leads to sepsis and mechanical ventilation-associated pulmonary fibrosis (S-MVPF). This study aimed to explore the mechanism of S-MVPF concerning integrin ß3 activation in glycometabolic reprogramming of lung fibroblasts. We found that MV exacerbated sepsis-associated pulmonary fibrosis induced by lipopolysaccharide, which was accompanied by proliferation of lung fibroblasts, increased deposition of collagen in lung tissue, and increased procollagen type I carboxy-terminal propeptide in the bronchoalveolar lavage fluid. A large number of integrin ß3- and pyruvate kinase M2-positive fibroblasts were detected in lung tissue after stimulation with lipopolysaccharide and MV, with an increase in lactate dehydrogenase A expression and lactate levels. S-MVPF was primarily attenuated in integrin ß3-knockout mice, which also resulted in a decrease in the levels of pyruvate kinase M2, lactate dehydrogenase A, and lactate. In conclusion, MV aggravated sepsis-associated pulmonary fibrosis, with glycometabolic reprogramming mediated by integrin ß3 activation. Thus, integrin ß3-mediated glycometabolic reprogramming might be a potential therapeutic target for S-MVPF.

Effect of sevoflurane anesthesia to neonatal rat hippocampus by RNA-seq.

BACKGROUND: Sevoflurane is an inhalational anesthetic for the induction and maintenance of general anesthesia in pediatric surgery. However, few studies have paid attention to the multiple organ toxicity and the mechanism behind it. METHODS: Inhalation anesthesia neonatal rat model were realized by exposing to 3.5% sevoflurane. RNA-seq was performed to find out how inhalation anesthesia affects the lung, cerebral cortex, hippocampus, and heart. Validation of RNA-seq results by QPCR after animal model establishment. Tunel assay detects cell apoptosis in each group. CCK-8, cell apoptosis assay and western blot assay validation of the role of siRNA-Bckdhb in the action of sevoflurane on rat hippocampal neuronal cells. RESULTS: There are significant differences between different groups, especially the hippocampus and cerebral cortex. Bckdhb was significantly up-regulated in the hippocampus with sevoflurane-treated. Pathway analysis revealed several abundant pathways related to DEGs, e.g., protein digestion and absorption and PI3K-Akt signaling pathway. A series of cellular and animal experiments showed that siRNA-Bckdhb can inhibit the reduction of cellular activity caused by sevoflurane. CONCLUSION: Bckdhb interference experiments indicated that sevoflurane induces hippocampal neuronal cells apoptosis by regulating Bckdhb expression. Our study provided new insights into the molecular mechanism of sevoflurane-induced brain damage in pediatrics.