Effect of pre-pregnancy obesity on trimester-specific thyroid dysfunction / 上海预防医学

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

A case-control study on gut microbiota diversity and species composition in obese/overweight children aged 2-6 years in Shanghai / 环境与职业医学

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

Value of the expression levels of complement-3a receptor 1 and neutrophil extracellular traps in predicting sepsis-induced coagulopathy / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical value of complement-3a receptor 1 (C3aR1) and neutrophil extracellular traps (NETs) in predicting sepsis-induced coagulopathy (SIC).@*METHODS@#A prospective study was conducted among 78 children with sepsis who attended Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2022 to June 2023. According to the presence or absence of SIC, they were divided into two groups: SIC (n=36) and non-SIC (n=42) . The two groups were compared in terms of clinical data and the levels of C3aR1 and NETs. The factors associated with the occurrence of SIC were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the performance of C3aR1 and NETs in predicting SIC.@*RESULTS@#Compared with the non-SIC group, the SIC group had significantly higher levels of C-reactive protein, interleukin-6 (IL-6), interleukin-10, C3aR1, and NETs (P<0.05). The multivaiate logistic regression analysis showed that the increases in C3aR1, NETs, and IL-6 were closely associated with the occurrence of SIC (P<0.05). The ROC curve analysis showed that C3aR1 combined with NETs had an area under the curve (AUC) of 0.913 in predicting SIC (P<0.05), which was significantly higher than the AUC of C3aR1 or IL-6 (P<0.05), while there was no significant difference in AUC between C3aR1 combined with NETs and NETs alone (P>0.05).@*CONCLUSIONS@#There are significant increases in the expression levels of C3aR1 and NETs in the peripheral blood of children with SIC, and the expression levels of C3aR1 and NETs have a high clinical value in predicting SIC.

Research progress concerning prevention and treatment of tension blisters after fracture / 中华创伤骨科杂志

This paper reviews the research progress concerning the prevention and treatment of tension blisters after fracture. There are 8 preventive measures to reduce the incidence of fracture tension blisters, such as correct identification of the high risk factors for fracture blister, immobilization and fixation, and elevation of the affected limb. There are 4 treatments: blister aspiration, deroofment, leaving the blister intact, and negative pressure wound therapy. This review is to provide useful reference for those who need construction of clinical protocls for prevention and treatment of fracture tension blisters.

Advances in the establishment and evaluation of animal models of secondary lymphedema / 中华显微外科杂志

Secondary lymphedema is a chronic progressive disease caused by the obstruction of lymphatic reflux, which leads to a series of secondary affection. There is no cure at present. Exploring the pathogenesis and treatment of lymphedema is based on animal models that mimic the pathophysiology of chronic lymphedema in humans. Currently, there are many known animal models of lymphedema, such as the limb lymphedema model of mice, dogs and other animals, and the rabbit ear lymphedema model. But most of them cannot induce the persistent and stable lymphedema temporarily, which lead to a deadlock in the related research progress. Therefore, it is necessary to improve and even create new animal models of lymphedema. This paper summarises the progress of relevant literature and provides references for further improving the establishment of a lymphedema animal model. It also summarise existing methods for evaluating lymphedema or lymphatic vessel function to provide an evaluation tool for modified or new animal models.

Analysis on the Social Advantages and Practical Paths of Integrating Medical Social Work Services in the Medical Field / 中国医学伦理学

There are some issues in the process of patient treatment in the medical field, such as knowledge inequality, difficulties in doctor-patient trust and interdisciplinary cooperation, disciplinary barriers, excessive diagnosis and treatment, and structural imbalance of medical resources. In response to these issues, combined with the advantages of conceptual integration, professional integration, and resource integration of medical social work, this paper proposed a practical path for integrating medical social work services in the medical field. The main paths include micro path that systematization, comprehensiveness, and personalization of patient’s diagnosis and treatment process, the integration of intermediary path that integration of disciplinary and professional perspectives, concepts, and practices, and macro path that collaboration and coordination among society, community, and healthcare systems.

A multi-cancer risk prediction model which constructed based on H4C6 methylation level and cfDNA concentration / 安徽医科大学学报

Objective@#To explore the difference in H4 clustered histone 6(H4C6) methylation level and circulating cell-free DNA (cfDNA) concentration between 94 normal group and 122 tumor groups (65 patients with lung cancer，22 patients with gastric cancer，23 patients with colorectal cancer，and 12 patients with liver cancer) ，and the age of total 216 subjects were between 18 and 85 years old．To construct a cancer risk prediction model based on H4C6 methylation level and cfDNA concentration and evaluate the predictive performance of the model．@*Methods@#cfDNA was extracted from blood samples using magnetic beads．Qubit 4. 0 fluorescence quantitative meter was used to detect the concentration of cfDNA. Real-time quantitative PCR( RT-qPCR) technology was used to detect the methylation level of H4C6 in cfDNA．Logistic regression algorithm was used to construct a cancer risk prediction model of H4C6 methylation level combined with cfDNA concentration．The accuracy of the model was assessed using receiver operating characteristic (ROC) curve and calibration curve．The clinical benefit of the model was as- sessed using decision curve analysis (DCA) . @*Results@#The model was constructed by combining H4C6 methylation level and cfDNA concentration to distinguish lung cancer，liver cancer，colorectal cancer，gastric cancer，pancancer from healthy control group had the area under curve (AUC) of 0. 769，0. 988，0. 934，0. 922，0. 830，respectively．The mean absolute error of the calibration curve was less than 0. 05 ; the net benefit of the DCA curve was greater than 0．@*Conclusion@#The cancer risk prediction model based on H4C6 methylation level and cfDNA concentration has good predictive performance，which helps to provide reasonable and effective suggestions for preclinical decision-making，and ultimately may provide patients with targeted and personalized cancer detection and diagnosis program.

Preoperative risk factors for early extremity blood supply after repair of major arterial injury / 中华创伤骨科杂志

Objective:To investigate the preoperative risk factors affecting early extremity blood supply after repair of major arterial injury so as to provide clues for prevention of limb ischemia.Methods:The clinical data were retrospectively analyzed of the 139 patients (140 extremities) with major extremity arterial injury who had been admitted to Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, The First Hospital Affiliated to Sun Yat-sen University from January 2003 to December 2019. There were 112 males and 27 females, with a mean age of 30 (20, 44) years. The primary outcome was the early status of blood supply to the injured extremity (48 hours after surgery). Univariate analysis was conducted of such factors as gender, age, ischemia time, injury mechanism, injury site, fracture, soft tissue lesion, and duration of surgery. The significant factors ( P<0.1) were then analyzed by logistic regression, and P<0.05 was considered statistically significant. Results:Ischemia happened in 44 (31.4%, 44/140) extremities within 48 hours after surgery. There were significant differences in injury mechanism, ischemia time, fracture, and soft tissue lesion between patients with and without postoperative extremity ischemia ( P<0.05). Logistic regression analysis indicated that blunt injury ( OR=5.639, 95% CI: 1.068 to 29.761, P=0.042) and soft tissue lesion ( OR=12.568, 95% CI: 3.402 to 46.431, P<0.001) were significant preoperative risk factors affecting the early blood supply after repair of major extremity arterial injury. Conclusion:As blunt injury and soft tissue defect are preoperative risk factors for early extremity ischemia after repair of major extremity arterial injury, surgeons should pay more attention to them when assessing patients and making repair protocols.

Analysis of influencing factors on surgical outcome and exploration of technical principles during pancreaticojejunostomy / 中华外科杂志

Pancreaticojejunostomy is the most common anastomosis following pancreaticoduodenectomy and middle pancreatectomy. The detailed surgical technics of pancreaticojejunostomy vary dramatically, but none of them can achieve zero fistula rate. In recent years,with the development of new surgical concept,application of new surgical technology, high-tech materials and instruments,the incidence of pancreatic fistula has decreased. At the same time,researches on investigating the risk factors of pancreaticojejunostomy are gradually deepening. Based on years of surgical experience on pancreaticojejunostomy and current literatures, this paper analyzes the factors affecting the effect of pancreaticojejunostomy, such as the patient's basic physical state,pancreatic texture and diameter of the pancreatic duct,pathology and course of the disease,surgical technology and perioperative management,and summarizes six technical principles for pancreaticojejunostomy to be shared with surgical comrades:appropriate tension,protection of blood supply,hermetic closure of pancreatic section,accurate connection of pancreatic duct and intestinal mucosa,individualization,learning and accumulation of experience.

Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Applications and constructions of benzazepine scaffolds in drug molecular design / 药学学报

Benzazepine is a kind of fused ring structure, which is composed of nitrogen-containing seven-membered ring and benzene ring. The introduction of benzazepine scaffolds into compounds can not only adjust the physicochemical properties, maintain or enhance the biological activities of the compounds, but also improve the pharmacokinetic properties, increase the brain permeability, and reduce the toxicity of hERG of the compounds, which is one of the privileged scaffolds for rational design and structural optimization of drug molecules. Benzazepine scaffolds can be constructed by different synthetic methods such as Dickmann condensation reaction, Mitsunobu reaction, Pictet-Spengler reaction, CMD reaction, multicomponent reactions (MCRs), metal catalysis reactions and asymmetric catalysis etc., which play an important role in enriching the structure diversity of drug molecules.

Construction of prediction model for early screening in male patients with gastric cancer based on cell －free DNA methylation and machine learning / 安徽医科大学学报

Objective @#To construct a cell-free DNA ( cfDNA) methylation model for early screening in male pa- tients with gastric cancer by using novel cfDNA methylation detection technology．@*Methods @#Methylation informa- tion of the whole genome of gastric cancer patients were detected by cell-free methylated DNA immunoprecipitation and highthroughput sequencing ( cfMeDIP-seq ) technology and locate gastrogenic cfDNA． Then bioinformation methods were used to extract specific methylation labels which could distinguish GC patients and establish diagnosis model by random forest algorithm. Related validation clinical researches were also conducted. @*Results @#63 most sig- nificant DMR were selected to construct the cfDNA methylation model based on GC samples and normal control samples，the goal sensitivity was above 85 percent while the goal specificity was above 95% ．The sensitivity and specificity of the validation set were 98. 7% and 99. 0% while the area under curve(AUC) was 0. 999．@*Conclusion@#The cfDNA methylation model constructed in this study has good performance in predicting GC.

Correlation between endoscopic ultrasonographic features and pathological risk grade of gastric stromal tumors / 中华消化内镜杂志

To investigate the correlation between different endoscopic ultrasonographic signs and pathological risk grade of gastric stromal tumors. Data of 89 patients with gastric stromal tumors confirmed by pathology and immunohistochemistry who underwent gastroscopy and endoscopic ultrasonography in Zhongnan Hospital of Wuhan University from March 2013 to December 2017 were retrospectively analyzed. The endoscopic ultrasonographic characteristics of gastric stromal tumors with different risk degrees were compared. Among the 89 cases, 63 were very low-risk grade, 21 were low-risk grade, and 5 were intermediate-risk grade. Tumor size, echo homogenicity, ulcer, with or without regular boundary, and cystic change were correlated with tumor risk grade ( P<0.05). Endoscopic ultrasonography is helpful to predict risk grade of gastric stromal tumors before surgery.

Bone grafts for scaphoid fracture nonunion: a review of research advances / 中华创伤骨科杂志

In all the carpal fractures, scaphoid fracture is the most common in clinic (from 60% to 70% in proportion) and likely leads to nonunion. If nonunion is not treated in time, it probably causes instability of the scaphoid lunate joint, further leading to scapholunate advanced collapse. Its comprehensive manifestations include degenerative arthropathy of radial styloid process, radial scaphoid joint, capitulolunate joint and even total wrist joint, eventually leading to wrist joint dysfunction. Therefore, more and more attention has been paid to treatments of scaphoid fracture nonunion. Bone grafting is the most common practical treatment, but new surgical procedures have emerged in recent years. This article thus reviews the research advances in bone grafting for scaphoid fracture nonunion, commenting on the advantages and disadvantages of various techniques.

RSC96 proliferation and migration induced by Etifoxine through up-regulating CELSR2 expression / 中华显微外科杂志

Objective:To observe the effects of Etifoxine on proliferation and migration of RSC96 (Schwann cells of rat) and its potential molecular mechanisms.Methods:From March, 2020 to October, 2020, cultured RSC96 were treated with 20 μmol/L Etifoxine and saline respectively for 48 h. Cell proliferation was tested by EdU assay using Cell-Light EdU DNA Cell Proliferation Kit and the capability of migration was determined by wound healing assay and a transwell system. To investigate the effects of Etifoxine on CELSR2 protein expression, after treated with different concentrations of Etifoxine at 0-20 μmol/L for 48 hours, cells were subject to Western blot analysis to verify the expression of CELSR2 protein. To explore whether CELSR2 would be a potential target of Etifoxine, siRNA targeting CELSR2 and control siRNA groups were transfected into 20 μmol/L Etifoxine-treated RSC96 using Lipo3000. Again, the cell proliferation and migration of were investigated after 48 hours with the same procedures. The two-tailed Mann-Whitney U test was employed in statistical assessment.Results:EdU results showed a significant higher percentage of Edu-positive (proliferating) cells in the 20 μmol/L Etifoxine-treated group than the control group[(36.30±3.09)% vs (19.40±2.50)%, P<0.05]. Transwell migration assay demonstrated that the number of 20 μmol/L Etifoxine-treated RSC96 which migrated through the transwell membrane was higher than saline group, with significant statistical difference [(132.30±6.77) vs(65.33±7.37), P<0.05]. The percentage of reduction of wound area measured at 24 hours and 36 hours after the scratch also showed the similar results [(30.67±2.16)% vs (23.00±2.61)%; (86.00±2.19)% vs (49.67±2.81)%, respectively, P<0.05]. Besides, with increase of the concentration of etifoxine, the expression of CELSR2 showed an trend of increase in RSC96 ( P<0.05), but no significant statistical difference was found between 10 μmol/L and 20 μmol/L groups ( P>0.05). Interestingly, the rate of cell proliferation, the number of migrating cells and the percentage of wound area reduction of RSC96 in which were treated by Etifoxine and transfected with CELSR2 siRNA were significantly decreased compared with the control siRNA treatment ( P<0.05). Conclusion:Etifoxine could promote proliferation and migration of RSC96. Upregulation of CELSR2 protein expression in RSC96 is associated with the Etifoxine-induced enhancement of cell proliferation and migration.

Limb salvage for Gustilo III C open fracture of left humerus with limb ischemia and wound infection by microsurgery: A case report / 中华显微外科杂志

Report a case sustained Gustilo type III C open fracture of the left humerus with brachial artery injury who has limb ischemia and wound infection after operation in June, 2014. To salvage the limb, performed cross limb vessel transfer to restore blood supply at one-stage. After multiple debridement, Flow-through flap transfer was performed for definitive reconstruction of the arterial injury and repair the wound in secondary stage. In the 3rd stage, cutting the pedicle of transposition vessels. Follow-up at 1 year after surgery, the patient's left upper limb had survived with limited movement and confirmed Flow-through the vessel reconstruction using CTA.

Whole exome sequencing and trio analysis to broaden the variant spectrum of genes in idiopathic hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Dozens of genes are associated with idiopathic hypogonadotropic hypogonadism (IHH) and an oligogenic etiology has been suggested. However, the associated genes may account for only approximately 50% cases. In addition, a genomic systematic pedigree analysis is still lacking. Here, we conducted whole exome sequencing (WES) on 18 unrelated men affected by IHH and their corresponding parents. Notably, one reported and 10 novel variants in eight known IHH causative genes (AXL, CCDC141, CHD7, DMXL2, FGFR1, PNPLA6, POLR3A, and PROKR2), nine variants in nine recently reported candidate genes (DCAF17, DCC, EGF, IGSF10, NOTCH1, PDE3A, RELN, SLIT2, and TRAPPC9), and four variants in four novel candidate genes for IHH (CCDC88C, CDON, GADL1, and SPRED3) were identified in 77.8% (14/18) of IHH cases. Among them, eight (8/18, 44.4%) cases carried more than one variant in IHH-related genes, supporting the oligogenic model. Interestingly, we found that those variants tended to be maternally inherited (maternal with n = 17 vs paternal with n = 7; P = 0.028). Our further retrospective investigation of published reports replicated the maternal bias (maternal with n = 46 vs paternal with n = 28; P = 0.024). Our study extended a variant spectrum for IHH and provided the first evidence that women are probably more tolerant to variants of IHH-related genes than men.

Unfractionated heparin attenuates endothelial barrier dysfunction via the phosphatidylinositol-3 kinase/serine/threonine kinase/nuclear factor kappa-B pathway / 中华医学杂志(英文版)

BACKGROUND@#Vascular endothelial dysfunction is considered a key pathophysiologic process for the development of acute lung injury. In this study, we aimed at investigating the effects of unfractionated heparin (UFH) on the lipopolysaccharide (LPS)-induced changes of vascular endothelial-cadherin (VE-cadherin) and the potential underlying mechanisms.@*METHODS@#Male C57BL/6 J mice were randomized into three groups: vehicle, LPS, and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received subcutaneous injection of 8 U UFH 0.5 h before LPS injection. The lung tissue of the mice was collected for assessing lung injury by measuring the lung wet/dry (W/D) weight ratio and observing histological changes. Human pulmonary microvascular endothelial cells (HPMECs) were cultured and used to analyze the effects of UFH on LPS- or tumor necrosis factor-alpha (TNF-α)-induced vascular hyperpermeability, membrane expression of VE-cadherin, p120-catenin, and phosphorylated myosin light chain (p-MLC), and F-actin remodeling, and on the LPS-induced activation of the phosphatidylinositol-3 kinase (PI3K)/serine/threonine kinase (Akt)/nuclear factor kappa-B (NF-κB) signaling pathway.@*RESULTS@#In vivo, UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes (neutrophil infiltration and erythrocyte effusion, alveolus pulmonis collapse, and thicker septum), decreased the lung W/D, and increased protein concentration (LPS vs. LPS + UFH: 0.57 ± 0.04 vs. 0.32 ± 0.04 mg/mL, P = 0.0092), total cell count (LPS vs. LPS + UFH: 9.57 ± 1.23 vs. 3.65 ± 0.78 × 10/mL, P = 0.0155), polymorphonuclear neutrophil percentage (LPS vs. LPS + UFH: 88.05% ± 2.88% vs. 22.20% ± 3.92%, P = 0.0002), and TNF-α (460.33 ± 23.48 vs. 189.33 ± 14.19 pg/mL, P = 0.0006) in the bronchoalveolar lavage fluid. In vitro, UFH pre-treatment prevented the LPS-induced decrease in the membrane expression of VE-cadherin (LPS vs. LPS + UFH: 0.368 ± 0.044 vs. 0.716 ± 0.064, P = 0.0114) and p120-catenin (LPS vs. LPS + UFH: 0.208 ± 0.018 vs. 0.924 ± 0.092, P = 0.0016), and the LPS-induced increase in the expression of p-MLC (LPS vs. LPS + UFH: 0.972 ± 0.092 vs. 0.293 ± 0.025, P = 0.0021). Furthermore, UFH attenuated LPS- and TNF-α-induced hyperpermeability of HPMECs (LPS vs. LPS + UFH: 8.90 ± 0.66 vs. 15.84 ± 1.09 Ω·cm, P = 0.0056; TNF-α vs. TNF-α + UFH: 11.28 ± 0.64 vs. 18.15 ± 0.98 Ω·cm, P = 0.0042) and F-actin remodeling (LPS vs. LPS + UFH: 56.25 ± 1.51 vs. 39.70 ± 1.98, P = 0.0027; TNF-α vs. TNF-α + UFH: 55.42 ± 1.42 vs. 36.51 ± 1.20, P = 0.0005) in vitro. Additionally, UFH decreased the phosphorylation of Akt (LPS vs. LPS + UFH: 0.977 ± 0.081 vs. 0.466 ± 0.035, P = 0.0045) and I kappa B Kinase (IKK) (LPS vs. LPS + UFH: 1.023 ± 0.070 vs. 0.578 ± 0.044, P = 0.0060), and the nuclear translocation of NF-κB (LPS vs. LPS + UFH: 1.003 ± 0.077 vs. 0.503 ± 0.065, P = 0.0078) in HPMECs, which was similar to the effect of the PI3K inhibitor, wortmannin.@*CONCLUSIONS@#The protective effect of UFH against LPS-induced pulmonary endothelial barrier dysfunction involves VE-cadherin stabilization and PI3K/Akt/NF-κB signaling.

Effects and Mechanism of PARP Inhibitor Olaparib on the Expression of NKG2D Ligands in HL-60 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effects of Olaparib on natural killer cell activating receptor (NKG2D) ligands expression on human acute myeloid leukemia (AML) cell line HL-60, and to explore the molecular mechanism of Olaparib on HL-60 cells.@*METHODS@#After HL-60 cells in logarithmic growth phase were treated with Olaparib at different concentrations for different times (24, 48 h), the expression of NKG2D ligand on the surface of HL-60 cells was detected by flow cytometry. Western blot was used to dectect the expression of ERK expression in HL-60 cells. The killing effect of NK cells to HL-60 cells was detected by CFSE/PI method.@*RESULTS@#10 μmol/L Olaparib could upregulate the expression of NKG2D ligand on the surface of HL-60 cell at 24 and 48 hours, while 5 μmol/L Olaparib could induce up-regulation of the expression of ULBP-2 and ULBP-3 at 48 hours. Western blot analysis showed that ERK phosphorylation of HL-60 cells was enhanced after treating with Olaparib. The killing effect of NK cells to HL-60 cells could be enhanced by Olaparib, however, ERK inhibitor could suppress the killing effect of NK cells to HL-60 cells.@*CONCLUSION@#Olaparib can upregulate NKG2D ligands expression on the surface of HL-60 cells and enhance the cytotoxicity of NK cell to HL-60 cells. The mechanism may be related to Olaparib promoting ERK phosphorylation expression.

Therapeutic effect of ramipril and nifedipine on aged patients with hypertensive heart disease and its influence on cardiac function and inflammatory factor level ／ / 心血管康复医学杂志

Objective :To explore therapeutic effect of ramipril tablet and nifedipine controlled release tablet on aged patients with hypertensive heart disease and its influence on cardiac function and inflammatory factor level .Methods :A total of 186 aged patients with hypertensive heart disease were randomly equally divided into ramipril group ,nifedipine group and com‐bined treatment group (received ramipril + nifedipine).After eight weeks ,the therapeutic effect were observed and com‐pared among all groups.Results :Compared with before treatment , there were significant rise in LVEF ,cardiac index (CI) ,left ventricular early diastolic／late diastolic peak flow velocity (E／A) and 6min walking distance (6MWD) ,and sig‐nificant reductions in plasma levels of BNP ,CRP ,interleukin (IL)‐1 and IL‐6 after treatment in three groups , P＜0.01 all.Compared with ramipril group and nifedipine group after treatment ,there were significant rise in LVEF [ (43.44 ± 5.75)%,(43.41 ± 5.73)% vs.(49.89 ± 5.84)%] ,CI [(2.23 ± 0.64) L·min－1 ·m－2 ,(2.28 ± 0.69) L·min－1 ·m－2 vs.(2.87 ± 0.71) L·min－1 ·m－2 ] ,E／A [(0.87 ± 0.31) ,(0.90 ± 0.32) vs.(1.21 ± 0.39)] ,6MWD [(233.44 ± 38.95) m ,(236.45 ± 39.13) m vs.(299.77 ± 45.77) m] ,and significant reductions in plasma levels of BNP [ (199.67 ± 27.86) ng／L ,(194.55 ± 25.46) ng／L vs.(124.67 ± 29.45) ng／L] ,CRP [ (10.32 ± 3.18) mg／L ,(10.21 ± 2.89) mg／L vs. (8.35 ± 2.12) mg／L] , tumor necrosis factor (TNF)‐α [ (45.52 ± 14.56) pg／ml ,(45.45 ± 13.78) pg／ml vs.(37.86 ± 10.35) pg／ml] ,IL‐1 [ (6.34 ± 2.54) pg／ml ,(6.31 ± 2.31) pg／ml vs.(3.42 ± 1.89) pg／ml] and IL‐6 [ (6.71 ± 2.23) pg／ml ,(6.68 ± 2.11) pg／ml vs.(4.11 ± 1.75) pg／ml] , P＝0.001 all.Over all therapeutic effect of combined treatment was significantly higher than that of ramipril group ( Z＝ 3.747 , P＝ 0.001 ) and nifedipine group ( Z＝ 3.838 , P＝0.001).Conclusion :Ramipril combined nifedipine can improve therapeutic effect and cardiac function ,and reduce plasma levels of inflammatory factors in aged patients with hypertensive heart disease .