Objective Extracorporeal membrane oxygenation (ECMO) provides a treatment for patients with acute heart-lung failure. However, as an invasive procedure, it associated with high incidence of complications. It is important to a-vert and reduce the complications for improving the success rate in critically ill patients. We investigate the complications associated with ECMO after cardiac surgery and their management. Methods Clinical data from 117 postoperative patients[32 male, mean age (48.7 ± 16.5) years]supported with ECMO in the cardiovascular intensive care unit( ICU) from March 2005 to June 2008 were analyzed retrospectively. The cardiac operations they had undergone included coronary artery bypass grafting (n = 20), coronary artery bypass grafting and remodeling of left ventricle(n =9), coronary artery bypass grafting and valvular operation(n =5), repair of ventricular septal perforation following acute myocardial infarction(n =2), valvular operation( n = 46), heart/lung transplantation (n = 20/1), correction of congenital heart defects ( n = 10), and aortic operations ( n = 4). Venoarterial bypass was established in 110 patients by cannulation of the right atrium and femoral artery, and that of the right atrium and ascending aorta in 5 cases. Left atrial drainage to ECMO was added in 2 cases. Venovenous bypass was established in 2 patients with hypoxemia following cardiac surgery. Heparin was infused for maintaining the activated coagulation time (ACT) at 160 to 200 seconds for centrifugal pump(114 cases),and 200 to 250 seconds for roller pump(3 cases) to avoid thrombotic events until decannulation was achieved. Results The mean ECMO duration was 61 hours (range 3 to 225 hours). 48(41.0% ) patients died, 18 of them died of complications after weaning from circulatory assistant successfully. Complications occurred in 74 (63.2% ) patients included reoperation for hemostasis (n = 24), renal failure requiring renal replacement therapy (n =29), nosocomial infections ( n = 32) , ischemia in the extremities(n = 5), plasma leakage of oxygenators ( n = 29), gastroenteral hemorrhage ( n = 14), hemolysis ( n = 7 ), neurological complications ( n = 4) and centrifugal pump failure (n =1). Conclusion Bleeding is an early complication associated with ECMO support. The risk of nosocomial infection, renal failure and plasma leakage of oxygenators increases with the duration of ECMO support.

Background and Objectives: Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction ofarticular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. Methods: and Results: Real-time reverse transcription–polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3’-untranscribed region. Conclusions These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

Objective: To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis.Methods: Magnolia flower, xanthium fruit, astragalus root, paniculate cynanchum, scutellaria root, cicada molting, stephania root, small centipeda herb, and licorice root as traditional Chinese herbs are widely used to treat allergic rhinitis. With multiple database integration and entity grammar systems, a mo-lecular interaction network of traditional Chinese herbs for treating allergic rhinitis was established. Bioinformatics approaches were adopted to integrate relevant data and biological information by mul-tiple databases. Molecular interaction network of Chinese herbs for treating allergic rhinitis was con-structed based on entity grammar systems model. The network was then used for elucidating the anti-allergic rhinitis mechanism of the Chinese herbs on the molecular level. The subnetworks were also extracted to explicitly display the pathway and targets where effective components acted on. Results: Traditional Chinese herbs could influence various pathological aspects in allergic rhinitis including the production of pro-inflammatory substances, such as histamine and cytokine interleukin-4 (IL-4), interleukin-13 (IL-13), lowering immunoglobulin E (IgE) level or blocking antigen binding, altering the biological processes of IgE, modulating the balance of T helper (Th) or other cells by cell proliferation and differentiation, mediating cell-cell signaling and second-messenger-mediated signaling, stabilizing the cell membrane, and affecting regulation of cellular defense response. Conclusion: The research theoretically confirms the mechanism of anti-allergic rhinitis by traditional Chinese herbs, provides important fundamental research information for treatment of allergic rhinitis, and may serve as a reference for new drug development and effective ingredients of compatibility.

Objective:To investigate the stability of fat emulsions after the preparation of parenteral nutrient solution under different storage conditions.Methods:Standardized parenteral nutrient solution was used to prepare a total of 24 bags of nutrient solution with the same formula, except for that Group A (12 bags) contains 20% of medium and long chain fat emulsion (C6-24) while Group B contains 20% of C8-24. The preparations were stored under 2-8℃, 23-25℃, and 35-37℃ and were examined at 24h, 48h and 72h after preparation. The appearance, average size of fat particles, pH value of nutrient solution, and lipid peroxidation were investigated.Results:After storage at 4℃, 25℃ and 36℃ for 24h, 48h and 72h respectively, both groups of preparations showed no obvious change in appearance. There was no significant difference in pH ( P>0.05) nor lipid peroxidation ( P>0.05). Conclusion:Both kinds of fat emulsion are stable in terms of pH value, fat particle size and lipid peroxidation, and can be used for patients receiving intravenous nutrition support.

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.

Objective:To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods:According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results:Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects ( t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group ( F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group ( F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation ( F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group ( F=88.24, P<0.001). Conclusions:Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

Objective: To investigate the clinical, histologic and immunophenotypic features, genetic alterations and prognosis of the rare Xp11 neoplasm with melanocytic differentiation. Methods: Twenty-one cases were selected from the Department of Pathology, Jingling Hospital, Nanjing University School of Medicine from May 2008 to May 2018. The clinicopathologic, immunohistochemical, molecular analysis and follow-up details were collected. Results: There were 7 males and 14 females, with their ages ranging from 4 to 57 years (mean 32.8 years). The tumors were located in kidney (11 cases), pelvis (three cases), and in pancreas, retroperitoneum, adrenal gland, small intestine, prostate, cervix and appendix (one case each). Microscopically, most tumors shared similar morphology such as purely nested or sheet-like architectures separated by a delicate vascular network, purely epithelioid cells with clear to granular eosinophilic cytoplasm, lacks of papillary structures, spindle cell or fat components, uniform round to oval nuclei with small visible nucleoli, and in most of them (16/21) melanin pigment. Immunohistochemically, all cases showed moderately (2+) or strongly (3+) positive staining for TFE3 and Cathepsin K. HMB45 and Melan A were focally expressed in three of 21 cases, while the remaining cases showed typically moderate(2+) or strong (3+) expression. None of the cases were immunoreactive for SMA, desmin, CKpan, S-100 and PAX8. All cases showed TFE3 rearrangement using fluorescence in-situ hybridization (FISH). Fusion FISH assays detected SFPQ-TFE3 gene fusion in 16 cases, NONO-TFE3 gene fusion in two, ASPL-TFE3 and MED15-TFE3 gene fusions in one case each. Polymerase chain reaction and direct sequencing detected SFPQ-TFE3 gene fusion in nine cases, NONO-TFE3 and MED15-TFE3 gene fusions in one case each. Clinical follow-up was available for 15 patients for 12 to 74 months. Six patients died of the disease; and three had recurrences and/or metastases. Six patients were alive with no evidence of disease after initial resection. Conclusions Xp11 neoplasm with melanocytic differentiation has unique morphologic, immunophenotypic and genetic characteristics. The tumor is aggressive, and should be differentiated from Xp11 translocation RCC and perivascular epithelioid cell tumor.

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65^f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Objective: To establish a quantitative three-dimensional method based on intraoral scan to evaluate the changes of soft tissue, and to evaluate the changes of supracrestal gingival thickness (SGT) in skeletal class Ⅲ patients induced by periodontal regenerative and corticotomy surgery (PRCS). Methods: Twenty-two systematically and periodontally healthy skeletal class Ⅲ patients (4 males and 18 females, aged between 19 and 35 years), who were in need of combined orthodontic-orthognathic treatment and referred to the Department of Periodontology from the Department of Orthodontics and the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from January, 2018 to March, 2019, were collected in the study. The teeth involved were 112 anterior teeth (46 maxillary anterior teeth and 66 mandibular anterior teeth). PRCS in anterior tooth area was conducted before orthodontic decompensation. Probing depth (PD), bleeding index (BI) and keratinized gingiva width (KGW) were recorded before surgery and 6 months post-surgery. The intraoral digital impressions of maxillary and mandibular anterior teeth were obtained by 3-shape intraoral scanner before surgery and 6 months after surgery. The Standard Tessellation Language (STL) files were processed using Geomagic qualify 12.2 software to establish the soft tissue morphological measurement model, and to quantitatively analyze the changes of gingival thickness situated 1 to 2 mm apical to the free gingival margin on the median sagittal measurement plane. Results: Probing depth and bleeding index had no significant difference before and 6 months after operation (P>0.05). KGW in 6-month post-operation group [(5.18±2.32) mm] was significantly higher than that in pre-operation group [(4.22±1.43) mm] (P<0.05). Supracrestal gingival thickness situated 1 to 2 mm apical to the free gingival margin also significantly increased 6 months after surgery (P<0.05). The changes of gingival thickness situated 1 to 2 mm apical to the free gingival margin in the upper anterior area were (0.68±0.56) and (1.00±0.69) mm, respectively. The changes in the lower anterior area were (0.38±0.42) and (0.58±0.45) mm, respectively. The gingival changes of the upper anterior teeth were also significantly higher than those of the lower anterior teeth (P<0.01). Conclusions The described quantitative measurement based on intraoral scan could be an effective method for quantitative evaluation of the changes of soft tissue. PRCS could safely increase the supracrestal gingival thickness as well as KGW in skeletal class Ⅲ patients who were in need of combined orthodontic-orthognathic treatment.