Construction of a prognostic model for hepatocellular carcinoma based on pyroptosis-related genes / 中华肝脏病杂志

Objective: To study the construction of a prognostic model for hepatocellular carcinoma (HCC) based on pyroptosis-related genes (PRGs). Methods: HCC patient datasets were obtained from the Cancer Genome Atlas (TCGA) database, and a prognostic model was constructed by applying univariate Cox and least absolute shrinkages and selection operator (LASSO) regression analysis. According to the median risk score, HCC patients in the TCGA dataset were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox analysis, and nomograms were used to evaluate the predictive ability of the prognostic models. Functional enrichment analysis and immune infiltration analysis were performed on differentially expressed genes between the two groups. Finally, two HCC datasets (GSE76427 and GSE54236) from the Gene Expression Omnibus database were used to externally validate the prognostic value of the model. Univariate and multivariate Cox regression analysis or Wilcoxon tests were performed on the data. Results: A total of 366 HCC patients were included after screening the HCC patient dataset obtained from the TCGA database. A prognostic model related to HCC was established using univariate Cox regression analysis, LASSO regression analysis, and seven genes (CASP8, GPX4, GSDME, NLRC4, NLRP6, NOD2, and SCAF11). 366 cases were evenly divided into high-risk and low-risk groups based on the median risk score. Kaplan-Meier survival analysis showed that there were statistically significant differences in the survival time between patients in the high-risk and low-risk groups in the TCGA, GSE76427, and GSE54236 datasets (median overall survival time was 1 149 d vs. 2 131 d, 4.8 years vs. 6.3 years, and 20 months vs. 28 months, with P = 0.000 8, 0.034 0, and 0.0018, respectively). ROC curves showed good survival predictive value in both the TCGA dataset and two externally validated datasets. The areas under the ROC curves of 1, 2, and 3 years were 0.719, 0.65, and 0.657, respectively. Multivariate Cox regression analysis showed that the risk score of the prognostic model was an independent predictor of overall survival time in HCC patients. The risk model score accurately predicted the survival probability of HCC patients according to the established nomogram. Functional enrichment analysis and immune infiltration analysis showed that the immune status of the high-risk group was significantly decreased. Conclusion: The prognostic model constructed in this study based on seven PRGs accurately predicts the prognosis of HCC patients.

Quality assessment indictors and benchmarks for pancreatic surgery / 中华外科杂志

Pancreatic surgery is the most complex type of abdominal surgery,with high technical requirements and long learning curve,and the quality of surgery is directly related to the prognosis of the patients. In recent years,more and more indicators have been used to evaluate the quality of pancreatic surgery,such as operation time,intraoperative blood loss,morbidity,mortality, prognosis and so on,and different evaluation systems have been established,including benchmarking,auditing,outcome evaluation based on risk factor adjustment and textbook outcomes. Among them,the benchmark is the most widely used to evaluate surgical quality and is expected to become the standard for comparison among peers. This article reviews existing quality evaluation indicators and benchmarks for pancreatic surgery and anticipates its future application prospects.

Expression pattern of MMP-12 in long-term optic nerve regeneration induced by lens injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.

Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification / 中国中药杂志

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.@*METHODS@#H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.@*RESULTS@#Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).@*CONCLUSION@#Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes / 中华劳动卫生职业病杂志

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Clinical characteristics of anomalous aortic origin of a coronary artery in children / 中华儿科杂志

Objective: To analyze the clinical characteristics, diagnosis and treatment of anomalous aortic origin of a coronary artery (AAOCA) in children. Methods: There were 17 children diagnosed with AAOCA from January 2013 to January 2022 in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine.Their clinical manifestations, laboratory and imaging data, treatment and prognosis were retrospectively analyzed. Results: These 17 children included 14 males and 3 females, with the age of (8.7±3.5) years. There were 4 anomalous left coronary artery (ALCA) and 13 anomalous right coronary artery (ARCA). Seven children presented with chest pain or chest pain after exercise, three patients presented with cardiac syncope, one complained chest tightness and weakness, and the other six patients had no specific symptoms. Cardiac syncope and chest tightness occurred in patients with ALCA. Fourteen children had the dangerous anatomical basis of myocardial ischemia caused by coronary artery compression or stenosis on imaging. Seven children had coronary artery repair, of whom two were ALCA and five were ARCA. One patient had received heart transplantation because of heart failure. The incidence of adverse cardiovascular events and poor prognosis in ALCA group was higher than that in ARCA group (4/4 vs. 0/13, P<0.05). They were followed up in the outpatient department regularly for 6 (6, 12) months; except for the one who lost visit, the rest of the patients had a good prognosis. Conclusions: Cardiogenic syncope or cardiac insufficiency usually occurs in ALCA, and adverse cardiovascular events and poor prognosis are more common in ALCA than in ARCA. Early surgical treatment should be considered for children with ALCA and ARCA accompanied by myocardial ischemia.

Research progress on ferroptosis regulated by glycolysis-fatty acid metabolism in metabolic diseases / 药学学报

In metabolic diseases, the accumulation of reactive oxygen species and oxidative stress are closely associated with ferroptosis. As a key regulatory factor, the imbalance between glycolysis and fatty acid metabolism can participate in ferroptosis directly or indirectly, thereby regulating the occurrence and development of various metabolic diseases. The essence of ferroptosis is a new regulatory cell death mode, which is caused by the excessive accumulation of iron-dependent lipid peroxide. It is closely related to glycolysis and fatty acid metabolism, which plays an important role in metabolic diseases. This regulatory cell death mode is significantly distinguished from other programmed cell death modes and has unique changes in cell morphology, symbolic characteristics and mechanisms. This paper first illustrates the main mechanism of glycolysis and fatty acid metabolism imbalance in the occurrence of ferroptosis, then reviews the research progress of ferroptosis in tumor, diabetes, rheumatoid arthritis and other metabolic diseases, and finally reveals the internal connection between glycolysis-fatty acid metabolism imbalance and ferroptosis, as well as its impacts on metabolic diseases, which provide new strategies for the prevention and treatment of metabolic diseases.

Cinnamomi Cortex Regulates Incretin Effect in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1 / 药学学报

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

Mechanical circulatory support combined with immunomodulation treatment for patients with fulminant myocarditis: a single-center real-world study / 中华心血管病杂志

Objective: To investigate the relationship between the mechanical circulatory support (MCS) combined with immunomodulation and the prognosis of patients with fulminant myocarditis. Methods: This is a retrospective study. A total of 88 patients with fulminant myocarditis admitted to Dongguan Kanghua hospital from Aug. 2008 to Dec. 2020 were included. Medical histories, results of laboratory tests, treatment regimens and clinical outcomes of these patients during their hospitalization were collected from the medical record system. According to the treatment methods, the patients were divided into MCS+immunomodulation group (38 cases), MCS group (20 cases) and traditional treatment group (30 cases). Patients in the MCS+immunomodulation group received intra-aortic balloon pump (IABP) or IABP combined with extracorporeal membrane oxygenation (ECMO) and immunoglobulin or glucocorticoid. Patients in the MCS group only received mechanical circulatory support. Patients in the traditional treatment group received neither mechanical circulatory support nor immunomodulatory therapy, and only used vasoactive drugs and cardiotonic drugs. The in-hospital mortality and length of stay were compared among the three groups. Results: A total of 88 patients with fulminant myocarditis aged (35.0±10.8) years were included, and there were 46 males (52.3%). The mortality of MCS+immunomodulation group (7.9% (3/38) vs. 56.7% (17/30), P=0.001 2) and MCS group (30.0% (6/20) vs. 56.7% (17/30), P=0.002 8) were lower than that of traditional treatment group. Compared with the MCS group, the in-hospital mortality in the MCS+immunomodulation group was lower (P=0.005 4). The most common cause of death was multiple organ dysfunction syndrome (MODS). The constituent ratios of death in MCS+immunomodulation group, MCS group and traditional treatment group were 3/3, 4/6 and 12/17, respectively. The incidence of MODS in the MCS group (20% (4/20)) and the traditional treatment group (40% (12/30)) was significantly higher than that in the MCS+immunomodulation group (7.9% (3/38)) (both P<0.01). In discharged patients, the hospitalization time of MCS+immunomodulation group was shorter than that of traditional treatment group ((13.4±5.5)d vs. (18.5±7.4)d, P<0.05) and MCS group ((13.4±5.5)d vs. (16.9±8.5)d, P<0.05). Conclusion: MCS combined with immunomodulatory therapy is associated with lower in-hospital mortality and shorter hospital stay in patients with fulminant myocarditis.

An adjustable anti-snoring device improves brain oxygen supply and chronic cerebral circulation insufficiency in patients with obstructive sleep apnea syndrome / 中国基层医药

Objective:To investigate the efficacy of an adjustable anti-snoring device in improving brain oxygen supply and chronic cerebral circulation insufficiency in patients with obstructive sleep apnea syndrome (OSAS).Methods:Thirty-four patients with OSAS who received treatment in Huidong People's Hospital from January to September 2018 were included in the OSAS group. An additional 34 sex- and age-matched healthy volunteers who concurrently received physical examination were included in the control group. Apnea-hypopnea index score for each patient was determined by polysomnography. Cerebral blood flow velocity was measured by transcranial Doppler ultrasonography. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate was obtained by electrocardiography. Arterial oxygen saturation (SaO 2) was obtained using pulse oximetry. Blood pressure was obtained by an automatic sphygmomanometer. Peripheral and cerebral hemodynamics of patients with OSAS were measured. Nighttime sleep quality of patients was assessed using polysomnography. Lateral projection of the skull was photographed using an X-ray machine for correcting measurement results. Results:There were no significant differences in sex and age between OSAS and control groups (both P > 0.05). Body mass index, Apnea-hypopnea index score and the percentage of time spent at SaO 2 below 90% in the OSAS group were significantly higher than those in the control group (all P < 0.05). The lowest SaO 2 value in the OSAS group was significantly lower than that in the control group ( P < 0.05). Heart rate and forearm blood flow in the OSAS group were (76.27 ± 9.34) beats/min and (7.24 ± 3.13) mL·100 mL -1·min -1, respectively, which were significantly higher than those in the control group [(65.42 ± 6.38) beats/min, (4.11 ± 1.25) mL·100 mL -1·min -1]. After treatment with an adjustable anti-snoring device, heart rate and forearm blood flow in the OSAS group were (66.17 ± 4.53) beats/min and (4.54 ± 3.26) mL·100 mL -1·min -1, respectively, which were significantly lower than those in the control group ( F = 2.66, 0.85, both P < 0.05). Peripheral oxygen saturation, tissue oxygen saturation, and total hemoglobin in the OSAS group were significantly lower than those in the control group. These indexes in the anti-snoring device treatment group were significantly higher than those in the OSAS group ( F = 12.33, 13.57, 14.22, all P < 0.05). The number of snorings and number of wake-ups from sleep in the anti-snoring device treatment group were significantly lower compared with those in the OSAS group ( χ2 = 13.14, 12.36, both P < 0.05).Palatopharyngeal diameter, glossopharyngeal diameter and laryngopharyngeal diameter in the anti-snoring device treatment group were significantly higher than those in the OSAS group, and they were almost close to the levels of healthy people ( t = 11.46, 15.13, 12.58, all P < 0.05). Conclusion:Adjustable anti-snoring device can improve brain oxygen supply and chronic cerebral circulation insufficiency in patients with OSAS, in particular with mild and moderate OSAS.

Effect of Alcohol Extract of Spore Powder of Lasiosphaera Calvatia on Wound Healing of Full-thickness Skin Defect in Mice / 中国实验方剂学杂志

ObjectiveTo compare the effect of different solvent extracts of spore powder and fruiting body of Lasiosphaera Calvatia on fibroblasts and wound healing of full-thickness skin defect， in order to screen the optimal medication part of Lasiosphaera Calvatia. MethodThe effect of water extract and alcohol extract of spore powder and fruiting body on cell proliferation and cell migration of mouse skin fibroblasts （MSF） were examined in vitro. Cell proliferation and activity test （CCK-8） method was used for cell proliferation， scratch assay was used for cell migration， flow cytometry was conducted to explore cell cycle， enzyme-linked immunosorbent assay （ELISA） was used to determine the production of collagen Ⅰ and Ⅲ. At the same time， a full-thickness skin defect wound model was established to investigate the therapeutic effect of different solvent extracts of spore powder. Ultraviolet-visible spectrophotometry was used to measure the contents of index components in different solvent extracts. ResultThe water extract of spore powder and fruiting body had certain cytotoxicity， while the alcohol extract could promote proliferation， migration and production of collagen Ⅰ and Ⅲ of MSF， and the effect of spore powder was significantly higher than that of fruiting body. When the concentration was 10 mg·L-1， the cell proliferation rate of alcohol extract of spore powder was as high as （159.22±15.95）%， and could promote MSF from the G0/G1 phase to S phase and G2/M phase with an increased proliferation index. The alcohol extract also promoted the migration of fibroblasts， secreted collagen Ⅰ and Ⅲ. On in vivo model， the alcohol extract of spore powder significantly accelerated wound healing on mice， effectively promoted the complete epithelialization of wound tissue， and generated new collagen fiber. The results of determination showed that the contents of polyphenols and flavonoids in the alcohol extract were higher than the alcohol extract of fruiting body. ConclusionThe alcohol extract of spore powder in Lasiosphaera Calvatia has active components in the treatment of wounds with good development prospect， and the medicinal components may be polyphenols and flavonoids.

Causal Relations between Exposome and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. @*Results@#We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. @*Conclusions@#The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.

Construction of a blood-brain barrier microfluidic chip model and evaluation of the permeability of active components in traditional Chinese medicine / 药学学报

A blood-brain barrier microfluidic chip platform for studying the permeability of active components in traditional Chinese medicine was developed. This model used primary human brain microvascular endothelial cells on a microfluidic chip consisting of two perpendicularly-crossing channels and a single layer porous polycarbonate membrane. The physiological shear stress in the human vasculature was also modeled in this device. Cell viability on the chip was monitored by cell staining and immunofluorescence staining. The cells spread well and the structure of an intercellular adhesion protein was satisfactory. The permeability of fluorescent tracers and three model drugs and the functional expression of P-glycoprotein (P-gp)on the blood-brain barrier were investigated. The results show that the apparent permeability coefficients (Papp) of the fluorescent tracers and three model drugs were consistent with those reported in the literature, and P-gp on the chip showed normal function, indicating that there was a complete structure and a functional BBB. The permeability of six active components of traditional Chinese medicine was investigated through this microfluidic chip and the drug concentration was determined by HPLC-MS/MS to obtain the Papp of each component. The Papp of corydaline was (4.51 ± 1.90)×10-7 cm·s-1, the Papp of tetrahydropalmatine was (9.10 ± 6.59)×10-7 cm·s-1, and the Papp of imperatorin was (9.38 ± 2.53)×10-7 cm·s-1; the concentration of isoimperatorin, baicalin and chlorogenic acid was below the limit of quantification, which suggested that isoimperatorin, baicalin and chlorogenic acid have poor permeability in this BBB chip. This blood-brain barrier microfluidic platform possesses a complete barrier function and near-physiological conditions and could be a valuable in vitro tool for drug permeability evaluation.

Research model integrating "both medicinal and adjuvant properties" for essential oils from Chinese medicinal: based on characterization of medicinal properties / 中国中药杂志

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.

Practice and analysis of empowerment reform of service invention in medical institutions / 中华医学科研管理杂志

Objective:To stimulate innovation vitality, the government promulgated the Pilot Implementation Plan for Granting Scientific and Technological Achievements Ownership or Long- term Use Right to Scientific Research Investigators. As one of the 40 pilot institutions, Beijing JiShuiTan Hospital attached great attention to it and, through the exploration and practice of pilot work, combined with the transformation of medical institutions' achievements Status quo, summarized the experiences of job scientific and technological achievements empowerment. Methods:Explored the mechanism and mode to empower researchers with the ownership or long-term right of service invention according to the policy review and case studies.Results:Developed hospital-level empowerment reform program and related supporting documents, Beijing JiShuiTan Hospital has completed the first empowerment work in Beijing.Conclusions:The reform of empowering scientific and technological achievements gives a new pathway to transform scientific and technological achievements in medical institutions, which will promote the transformation process of service invention-creation.

Comparative study on the efficacy of transumbilical single port and three port laparoscopic cholecystectomy in the treatment of calculous cholecystitis / 国际外科学杂志

Objective:To explore the efficacy of transumbilical single-port and three-port laparoscopic cholecystectomy (LC) in the treatment of calculous cholecystitis and its influence on immunological indicators and recovery of gastrointestinal function.Methods:One hundred and twenty patients with calculous cholecystitis who were treated in Suzhou Municipal Hospital of Anhui Province from June 2018 to June 2020 were prospectively selected as the research subjects, and the patients were randomly divided into single-hole group and three-hole group by random number table method. Group of 60 cases. The single port group used the transumbilical single port method LC, and the three port group used the transumbilical three port method LC. Compare the 24-hour pain VAS scores and the use of analgesics of the two groups of patients; compare the surgical indicators of the two groups of patients; compare the immunological indicators of the two groups before and after treatment; compare the two groups of patients The recovery of gastrointestinal function after operation; the occurrence of postoperative complications between the two groups was compared.Results:There was no statistically significant difference in intraoperative blood loss, hospitalization expenses, preoperative IgG, IgA, IgM levels, and postoperative complications between the two groups of patients ( P>0.05). The two groups of patients had significantly lower levels of IgG, IgA, and IgM after treatment ( P<0.05). In the single hole group, the pain VAS score, the use rate of analgesics, the time of hospitalization, the time of anal exhaust, the time of bowel sound returning to normal and the time of defecation were (4.65±0.61) points, 11.67%(7/60), (2.52±0.47) d, (13.65±3.72) h, (11.64±3.25) h and (20.31±4.12) h, respectively. The three-hole group were (6.87±0.58) points, 23.33% (14/60), (4.58±0.37) d, (17.36±4.12) h, (15.47±4.12) h and (26.48±4.25) h, respectively. It was significantly lower in the single-hole group than in the three-hole group ( P<0.05). In the single hole group, the operation time, abdominal wall cosmetology score and the levels of IgG, IgA, IgM after treatment were (76.36±4.58) min, (4.72±0.13) points, (1 108.48±42.65) mg/dL, (208.12±10.86) mg/dL, (154.65±8.72) mg/dL, respectively. The three-hole group were (51.37±5.25) min, (3.25±0.35) mg/dL, (1 072.39±28.42) mg/dL, (193.08±10.35) mg/dL and (145.28±8.42) mg/dL, respectively, and those in the single-hole group were significantly higher than those in the three-hole group ( P<0.05). Conclusion:Under the premise of proficiency in surgical operation techniques, the single-port method reduces pain, reduces the use of analgesics, has less impact on immunological indicators, recovers gastrointestinal function faster, and has better postoperative abdominal wall cosmetic effects.