[The diagnostic value of genetic testing in familial hypercholesterolemia in patients with premature myocardial infarction].

Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.

[Rosuvastatin acts on the lymphatic system to improve atherosclerosis].

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.

[Role of miR-106b-5p in the regulation of gene profiles in endothelial cells].

OBJECTIVE: To evaluate the role of miR-106b-5p in the regulation of gene expression in endothelial cells. METHODS: The Taqman low-density microRNAs (miRNAs) array (TLDA) was used to identify miRNA expression profiles in the plasma of patients with atherosclerotic coronary artery disease (CAD) (atherosclerosis group, n=9) and individuals without atherosclerotic CAD disease (control group, n=9). A weighed and undirected miRNA coexpression network analysis was performed to investigate the interactions among miRNAs in the two groups. MiR-106b-5p, whose coexpression pattern in atherosclerosis group was most different from that of control group, was further studied. Human umbilical vein endothelial cells (HUVEC) were transfected with miR-106b-5p mimic or negative control mimic, and Affymetrix GeneChip Human Transcriptome Array 2.0 was used to screen the differential gene expression profiles after transfection. And the signal transduction pathway of differential gene profiles was further analyzed in Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway database. After parsing the whole KEGG database, all differentially expressed genes involved pathways were extracted, and the hypergeometric distribution was used to calculate the pathway enrichment. RESULTS: The coexpression pattern of the patients with atherosclerosis (140 nodes, 1 154 edges) differed from that of the non-atherosclerosis control group (140 nodes, 612 edges). The analysis of array data with significant analysis of microarray (SAM) identified 746 significantly deregulated genes (fold change ≥ 1.5 and false discovery rate < 0.01) altered by overexpression of miR-106b-5p with miR-106b-5p mimic in HUVEC. By calculating the pathway enrichment, we found that multiple signaling pathways enriched in differential gene profiles were closely related to the process of formation and rupture of atherosclerotic plaque, including phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (PKB, also called Akt), mammalian target of rapamycin (mTOR), transforming growth factor-ß (TGF-ß), janus kinase / signal transducer and activator of transcription (Jak-STAT), tumor necrosis factor (TNF), toll like receptor (TLR) and hypoxia-inducible factor 1α (HIF-1α) and other signal pathways. CONCLUSION: The coexpression pattern of miRNAs in plasma of patients with atherosclerosis is more significantly changed than that of individuals without atherosclerotic disease. MiR-106b-5p, which shows the most significant difference between groups, targets multiple signal pathways in vascular endothelial cells, and might play an important role in the regulatory network of atherosclerotic gene expression.

Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/ß-catenin complex cross-talk.

OBJECTIVE: This study aimed to investigate the role of the Wnt/ß-catenin signaling pathway and E-cadherin/ß-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate cartilage degeneration. DESIGN: ß-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/ß-catenin signaling after ICMT application in vivo and in vitro. Co-immunoprecipitation was performed to examine the interaction between E-cadherin and ß-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/ß-catenin signaling and E-cadherin expression. RESULTS: ß-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/ß-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/ß-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and ß-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and ß-catenin proteins. CONCLUSIONS: ICMT promotes endplate cartilage degeneration via activation of Wnt/ß-catenin signaling and suppression of physical protein-protein interactions between E-cadherin and ß-catenin.

[microRNA-126 delivered by microparticles mediates intercellular signal transmission].

OBJECTIVE: To investigate the role of microRNAs (miRNAs) in mediating intercellular signaling. METHODS: Microparticles (MP) from HUVEC and 293T were isolated by sequential centrifugation. THP-1 was co-cultured with microparticles. And then the migration of THP-1 was measured by transwell. real-time PCR and Western blotting were used to study the related mechanisms. RESULTS: Compared with the microparticles from 293T, MP from HUVEC could promote the migration of monocytes (P<0.05) and upregulate the expression of CXCR4 mRNA and protein (P<0.05). MiRNA-126 deficient MP could downregulate the migration of monocytes (P<0.05) and the expression of CXCR4 mRNA and protein (P<0.05) compared with miRNA-126 abundant MP. CONCLUSION: Microparticles from HUVEC could promote the migration of monocytes. As carriers, microparticles could mediate intercellular signaling.

Yuan-Hu Zhi Tong Prescription Mitigates Tau Pathology and Alleviates Memory Deficiency in the Preclinical Models of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by memory dysfunction, Aß plaques together with phosphorylated tau-associated neurofibrillary tangles. Unfortunately, the present existing drugs for AD only offer mild symptomatic cure and have more side effects. As such, developments of effective, nontoxic drugs are immediately required for AD therapy. Present study demonstrates a novel role of Chinese medicine prescription Yuan-Hu Zhi Tong (YZT) in treating AD, and it has substantiated the in vivo effectiveness of YZT in two different transgenic mice models of AD, namely P301S tau and 3XTg-AD mice. Oral treatment of YZT significantly ameliorates motor dysfunction as well as promotes the clearance of aggregated tau in P301S tau mice. YZT improves the cognitive function and reduces the insoluble tau aggregates in 3XTg-AD mice model. Furthermore, YZT decreases the insoluble AT8 positive neuron load in both P301S tau and 3XTg-AD mice. Using microarray and the "Connectivity Map" analysis, we determined the YZT-induced changes in expression of signaling molecules and revealed the potential mechanism of action of YZT. YZT might regulate ubiquitin proteasomal system for the degradation of tau aggregates. The research results show that YZT is a potential drug candidate for the therapy of tau pathogenesis and memory decline in AD.

[Nutritional support therapy during treatment of chronic critical illness].

Chronic critical illness (CCI) refers to a group of critically ill patients who survive the acute phase of intensive care, but with persistent organ dysfunction, thus entering a chronic period of continuous dependence on life support system, and still need to stay in intensive care unit (ICU) for a long time. Persistent inflammatory response-immunosuppression-catabolic syndrome (PICS) is the main pathophysiological feature of CCI. Three factors interact to form a vicious circle, leading to poor prognosis. Nutritional support therapy is a key link in the comprehensive treatment of CCI. Enteral nutrition (EN) should be started as soon as possible if conditions permit. If EN can not be implemented, temporary or transitional parenteral nutrition (PN) should be used, and EN should be added gradually in time. At the same time, the amount of PN should be gradually reduced. When EN meets more than 60% of patients' energy and protein requirements, PN can be considered to be discontinued. The main strategies and functions of CCI nutritional support therapy are as follows: strengthening high protein supply to correct negative nitrogen balance and inhibit catabolism, selecting branched chain amino acids (BCAA) to promote anabolism, using immunomodulators (arginine, ω3 polyunsaturated fatty acids) to improve immune suppression and inflammatory response, supplementing micronutrients (vitamins and trace elements) to counteract the decrease in intake and the increase in consumption, and adding probiotics to maintain the intestinal microecological balance, and so on. Reasonable nutritional support therapy not only improve malnutrition of CCI patients, but also help to reduce complications, thus speeding up rehabilitation, improving prognosis, shortening ICU hospitalization time, and even reducing mortality.

Effect and mechanism of andrographolide on the recovery of Pseudomonas aeruginosa susceptibility to several antibiotics.

Effectiveness and mechanism of action of andrographolide on the recovery of Pseudomonas aeruginosa susceptibility to antibiotics was investigated. In the presence of andrographolide, the Mueller-Hinton broth dilution method measured minimal inhibitory concentrations (MIC) of ceftazidine, cefpirome, chloramphenicol, L-ofloxacin, kanamycin, imipenem and meropenem. Real-time fluorescence quantitative polymerase chain reaction was used to determine mexB mRNA expressions in P. aeruginosa PAO1 strain and MexAB-OprM overexpressing strain. Relative mexB mRNA expression was detected in both strains incubated for 3 and 9 h. When andrographolide-treated groups were compared with controls, the MIC of ceftazidine, cefpirome, L-ofloxacin and meropenem for both strains decreased, and the relative mexB mRNA expression was significantly lower, although between andrographolide groups there were no significant differences. Compared with the inactivated quorum-sensing system, relative amounts of mexB mRNA in the PAO1 strain and MexAB-OprM overexpressing strain in the activated quorum-sensing system increased 10- and 30-fold, respectively. Andrographolide recovered P. aeruginosa susceptibility to antibiotics and reduced the MexAB-OprM efflux pump expression level.

Correlation between adiponectin polymorphism and atherosclerotic plaque compositions under intravascular ultrasound (IVUS).

OBJECTIVE: To discuss the correlation between polymorphism of rs266729 (-11377C/G, Cytosine/Guanine) (adiponectin promoter) site and atherosclerotic plaque compositions as well as related indicators under intravascular ultrasound (IVUS). PATIENTS AND METHODS: 76 patients with coronary heart disease from December 2014 to December 2016 were enrolled. The PCR-RFLP method was used to analyze the adiponectin gene polymorphism in rs266729 site. All the objects were divided into CC type group (n=26), CG type group (n=23), and GG type group (n=27) according to the results of polymorphism. The amount of lesions and length of lesion in the vessel were determined according to the images of coronary angiography. The indicators from each group, including minimum external elastic membrane area, the smallest lumen area, the patch area, the patch load, the lipid pool area, the lipid pool/plaque area, the fiber cap thickness, the reconstruction index, the positive reconstruction, the negative reconstruction and the patch character were measured according to the IVUS results. RESULTS: The baseline data from distinct the gene types showed no significant difference. The results of quantitative IVUS plaque analysis indicated a statistical difference of factors such as plaque area, plaque burden, lipid pool area, lipid pool/plaque area, and remodeling index between the CC and GG types (p<0.05). The levels of aminopeptidase N (APN), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), fasting serum insulin (FIN), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) among diverse groups presented statistical difference (p<0.05). Of note, the analysis results of IVUS qualitative components of plaque showed that soft plaque in CC group was 42.3% (11/26), which was significantly lower than GG group 11.1% (3/27) (p<0.05). The vascular remodeling ratio in CC group 26.9% (7/26) was also significantly decreased compared to that in GG group 66.7% (18/27) (p<0.05). The tubular and diffuse ratio in CC groups according to the comparison of diseased vessel, count, length of the lesion were 34.6% (9/26) and 42.3% (11/26), respectively. CONCLUSIONS: Our data on biochemical indicators demonstrates CC type gives rise to poor prognosis compared to GG type does, which suggests that close attention should be paid in the impact of adiponectin polymorphism on atherosclerotic plaque compositions.

[Evaluation of anastomotic effect with esophagogastrostomy covered by tongue-like sero-muscular flap of gastric wall in 1515 cases].

Esophagogastrostomy covered by tongue-like sero-muscular flap of gastric wall has already been performed in 1515 cases with esophageal cancer of middle or lower third segment over the last three years. All cases were of squamous cell carcinoma. The same anastomotic procedure was done in all cases by authors in different hospitals. In this series the operative mortality was 0.07%, there were 5 anastomotic leaks (0.33%), and no anastomotic stricture and reflux esophagitis happened within 6 months to 3 years after surgery. The operative procedure is described again in detail. The authors believe that this new anastomotic procedure is satisfactory and prospectively beneficial for improving the therapeutic effect and patients' living quality after operation.

[Effects of CCK-8 of hypothalamus on antral motility in rats].

Cholecystokinin-octapeptide (CCK-8) of 10 ng were injected into lateral hypothalamus (LH) and ventromedial hypothalamus (VMH) in conscious rats, both of which brought about inhibition of antral motility recorded by a strain gauge, the actions were partly antagonised by bilateral vagotomy, but blocked by intravenous infusion of atropine or regitine. It is suggested that both vagus and sympathetic nerves be involved in mediation of function of central CCK-8. In addition, the unit spontaneous discharges of neurons in vagal nuclei were attenuated while CCK-8 injected into LH. On the contrary, the antral motility was stimulated markedly by injection CCK-8-antiserum into LH, indicating that the endogenous CCK-8 in this area exercises a continuous restraint on antral motility in the basal state. CCK-8 cells both in LH and VMH were visualized by PAP method. It may be reasonable to refer this as the histological basis of the identical function on antral motility exercised by CCK-8 both in LH and VMH.

[Microcirculation in unphysiological flaps at early stage after operation: an experimental study].

Microcirculation and blood perfusion in unphysiological flaps were observed with rabbit ear microcirculation chamber. The microcirculation of the venous flap in two days after operation was reestablished mainly by diversion of blood flow through the "to and fro" movement of venous blood. Arteriovenous anastomoses were gradually opened, resulting in the microcirculation to restore normal perfusion, venous blood through the anastomoses into arteriole then to capillaries. The microcirculation of arterialized venous flaps was almost the same as that of the venous flaps. In two days after operation, the diversion of blood flow perfused the capillaries under high pressure, so that the flow velocity and rate were much faster and larger than those of the venous flaps. The microcirculation of venouslized arterial flap, nourished by venous blood through the arterial system, was the same as that of the physiological flap. But the capillaries were perfused venous blood flow, and the blood flow velocity and rate were much slower and smaller than those of the physiological flap.

[Clinical observation of cryotherapy in 242 cases of ocular and facial neoplasms].

242 patients of ocular and facial hemangioma, nevi, papilloma, etc. were treated with liquid nitrogen cryotherapy which satisfactorily removed the neoplasms in 97.2% of the cases, leaving essentially no scars, and the rest (2.8%) were improved. Pathological examinations confirmed that the neoplasms had been necrotized. There were no relapses in 97.7% of the cases after a follow-up of over 5 years. The author's experience was summarized in 9 points for good results of the treatment.

Estimating mercury emissions from a zinc smelter in relation to China's mercury control policies.

Mercury concentrations of flue gas at inlet/outlet of the flue gas cleaning, electrostatic demister, reclaiming tower, acid plant, and mercury contents in zinc concentrate and by-products were measured in a hydrometallurgical zinc smelter. The removal efficiency of flue gas cleaning, electrostatic demister, mercury reclaiming and acid plant was about 17.4%, 30.3%, 87.9% and 97.4% respectively. Flue gas cleaning and electrostatic demister captured 11.7% and 25.3% of the mercury in the zinc concentrate, respectively. The mercury reclaiming tower captured 58.3% of the mercury in the zinc concentrate. About 4.2% of the mercury in the zinc concentrate was captured by the acid plant. Consequently, only 0.8% of the mercury in the zinc concentrate was emitted to the atmosphere. The atmospheric mercury emission factor was 0.5 g t(-1) of zinc produced for the tested smelter, indicating that this process offers the potential to effectively reduce mercury emissions from zinc smelting.

Prognostic significance of PTEN expression in esophageal squamous cell carcinoma from Linzhou City, a high incidence area of northern China.

Decreased expression of tumor suppressor gene PTEN has been reported to be a poor prognostic indicator in a variety of human malignant tumors. The purpose of this study was to clarify the roles of PTEN in esophageal squamous cell carcinoma (ESCC) and the prognostic significance of PTEN protein expression. Sixty-four patients from a high incidence area of northern China who underwent esophagectomy for ESCC between January 1998 and December 1999 enrolled in this study. PTEN expression was assessed by immunohistochemistry in 64 primary cancers and 64 paired normal esophageal epithelium tissues. The positive rate and staining grade of PTEN protein expression was lower in the esophageal cancers than in paired adjacent normal esophageal epithelium (P < 0.001). PTEN expression correlated with tumor differentiation (P = 0.001), tumor infiltration depth (P = 0.015) and pTNM staging (P = 0.048). The 5-year survival rate in patients with PTEN positive expression was 82% compared to 39% in patients with PTEN negative expression (P = 0.0019). Our results show that the expression of PTEN is decreased in ESCC compared to normal esophageal epithelium. Therefore, PTEN may play an important role in carcinogenesis and the progression of ESCC in a high incidence area of northern China, and PTEN could serve as an important factor to predict clinical outcome and prognosis.