[Epidemiological characteristics and Spatial-temporal clustering of hand, foot and mouth disease in Shanxi province, 2009-2020].

Objective: To analyze the epidemiology and spatial-temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Shanxi province. Methods: The data of HFMD in Shanxi province from 2009 to 2020 were collected from notifiable disease management information system of Chinese information system for disease control and prevention and analyzed by descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis and spatio- temporal scanning analysis. Results: A total of 293 477 HFMD cases were reported in Shanxi province from 2009 to 2020, with an average annual incidence of 67.64/100 000 (293 477/433 867 454), severe disease rate of 5.36/100 000 (2 326/433 867 454), severe disease ratio of 0.79%(2 326/293 477), mortality of 0.015/100 000 (66/433 867 454), and fatality rate of 22.49/100 000 (66/293 477). The reported incidence rate, severe disease rate, mortality rate and fatality rate of HFMD showed decreasing trends. The main high-risk groups were scattered children and kindergarten children aged 0-5. The incidence of HFMD had obvious seasonal variation, with two peaks every year: the main peak was during June-July, the secondary peak was during September-October and the peak period is from April to November. A total of 13 942 laboratory cases were confirmed, with a diagnosis rate of 4.75% (13 942/293 477), including 4 438 (35.11%, 4 438/293 477) Enterovirus A71 (EV-A71) positive cases, 4 609 (33.06%, 4 609/293 477) Coxsackievirus A16 (CV-A16) positive cases, and 4 895 (31.83%, 4 895/293 477) other enterovirus positive cases. There was a spatial positive correlation (Moran's I ranged from 0.12 to 0.58, all P<0.05) and the spatial clustering was obvious. High-risk regions were mainly distributed in Taiyuan in central Shanxi province, Linfen and Yuncheng in southern Shanxi province, and Changzhi in southeastern Shanxi province. Spatial-temporal scanning analysis revealed 1 the most likely cluster and 8 secondary likely clusters, of which the most likely cluster (RR=2.65, LLR=22 387.42, P<0.001) located in Taiyuan and Jinzhong city, Shanxi province, including 12 counties (districts), and accumulated from April 1, 2009 to November 30, 2018. Conclusions: There was obvious spatial-temporal clustering of HFMD in Shanxi province, and the epidemic situation was in decline. The key areas were the districts in urban areas and the counties adjacent to it. Meanwhile, the monitoring and classification of other enterovirus types of HFMD should be strengthened.

[Analysis of clinical features and treatment of pyoderma gangrenosum].

Objective: To explore the clinical features and treatment of pyoderma gangrenosum (PG). Methods: A retrospective observational study was conducted. From January 2012 to July 2021, 25 patients with PG who met the inclusion criteria were admitted to Beijing Fucheng Hospital, including 16 males and 9 females, with the age of onset of disease being 14 to 75 years. Among them, the classification of PG identified 17 cases of ulcerative type, 6 cases of pustular type, 1 case of proliferative type, and 1 case of bullous type. Six patients were accompanied with systemic diseases, while 19 patients were not accompanied with systemic diseases. At the same time of systemic treatment with glucocorticoids, dressing changes or surgical skin grafting was performed on the wounds. The results of laboratory and histopathological examinations, the overall curative effects and follow-up of patients, the wound healing time of patients with negative and positive microbial culture results of wound secretion specimens, and the curative effects of patients with and without systemic diseases were analyzed. Results: The results of blood routine examination of 19 patients were abnormal, and all the immunological indexes were normal in all the patients; the microbial culture results of wound secretion specimens were positive in 14 patients; and the histopathological examination results of ulcer boundary tissue in 15 patients with rapid wound progress were mainly local tissue inflammatory changes. The wounds were cured in 17 patients, mostly healed in 7 patients, and not healed in 1 patient. After one-year's follow-up, the PG in 3 patients relapsed due to self-discontinuation of medication after discharge, and the wounds were healed gradually after adjustment of medication, while the remaining patients had no relapse. The days of wound healing in 14 patients with positive microbial culture results of wound secretion specimens were 21-55 days, and the days of wound healing in 11 patients with negative microbial culture results in wound secretion specimens were 20-54 days. In the 6 patients with systemic diseases, the wounds of 3 patients were cured, and the wounds of the other 3 patients were mostly healed. In the 19 patients without systemic diseases, the wounds of 14 patients were cured, the wounds of 4 patients were mostly healed, and the wound of 1 patient was not healed. Conclusions: The laboratory examination and pathological manifestations of patients with PG lacks characteristics, and their clinical manifestations are rich and diverse, thus PG can be easily misdiagnosed. The glucocorticoids combined with immunosuppressive therapy have good effects on PG. Surgical intervention can be performed on the wounds. Specifically, excessive debridement is not recommended in the acute phase, but skin grafting can be performed in the contraction phase.

[Roles of ten eleven translocation proteins family and 5-hydroxymethylcytosine in epigenetic regulation of stem cells and regenerative medicine].

The methylation of cytosine is one of the most fundamental epigenetic modifications in mammalian genomes, and is involved in multiple crucial processes including gene expression, cell differentiation, embryo development and oncogenesis. In the past, DNA methylation was thought to be an irreversible process, which could only be diluted passively through DNA replication. It is now becoming increa-singly obvious that DNA demethylation can be an active process and plays a crucial role in biological processes. Ten eleven translocation (TET) proteins are the key factors modulating DNA demethylation. This family contains three members: TET1, TET2 and TET3. Although three TET proteins have relatively conserved catalytic domains, their roles in organisms are not repeated, and their expression has significant cell/organ specificity. TET1 is mainly expressed in embryonic stem cells, TET2 is mainly expressed in hematopoietic system, and TET3 is widely expressed in cerebellum, cortex and hippocampus. This family catalyzes 5-methylcytosine to 5-hydroxymethylcytosine and other oxidative products, reactivates silenced-gene expression, in turn maintains stem cell pluripotency and regulates lineage specification. With the development of tissue engineering, organ transplantation, autologous tissue transplantation and artificial prosthesis have been widely used in clinical treatment, but these technologies have limitations. Regenerative medicine, which uses stem cells and stem cell related factors for treatment, may provide alternative therapeutic strategies for multiple diseases. Among all kinds of human stem cells, adipose-derived stem cells (ADSCs) are the most prospective stem cell lineage since they have no ethical issues and can be easily obtained with large quantities. To date, ADSCs have been shown to have strong proli-feration capacity, secrete numerous soluble factors and have multipotent differentiation ability. However, the underlying mechanism of the proliferation, secretion, acquired pluripotency, and lineage specific differentiation of ADSCs are still largely unknown. Some studies have explored the role of epigenetic regulation and TET protein in embryonic stem cells, but little is known about its role in ADSCs. By studying the roles of TET proteins and 5-hydroxymethylcytosine in ADSCs, we could provide new theoretical foundation for the clinical application of ADSCs and the stem cell-based therapy. In the future, combined with bioprinting technology, ADSCs may be used in tissue and organ regeneration, plastic surgery reconstruction and other broader fields.

[Retrospective analysis of the effectiveness of treating multi-space infection combined with descending necrotizing mediastinitis at oral maxillofacial and cervical region via multidisciplinary team collaboration].

Objective: To explore the strategy and experience for treating maxillofacial and cervical multi-space infection combined with descending necrotizing mediastinitis (DNM) via multidisciplinary team (MDT) collaboration. Methods: A total of 36 patients with maxillofacial and cervical multi-space infection complicated with DNM admitted to the First Affiliated Hospital of Zhengzhou University from July 2011 to July 2019 were included in the study. The clinical data of the patients were retrospectively analyzed, including gender, age, symptoms at admission, source of infection, preoperative and postoperative evaluation indicators, MDT strategy and prognosis. Results: There were 26 males and 10 females with an average age of (51.6±17.6) years (8-80 years). The course of disease before admission was (8.9±8.4) days (2-30 days). All patients were admitted with maxillofacial and neck swelling and pain as the main complaints. Odontogenic infection accounted for 39% (14/36), throat floor swelling and pain accounted for 25% (9/36) and unknown maxillofacial swelling accounted for 36% (13/36). There were 28 cases receiving surgical treatment, 26 cases were cured and discharged (72%), 10 cases died (28%). In the patients treated with multidisciplinary therapy (mainly by surgery), the white blood cell count, neutrophil percentage, C-reactive protein and procalcitonin levels were significantly improved compared with those at admission at each observation time point after operation (P<0.05). The length of stay was positively correlated with the levels of C-reactive protein (r=0.545, P<0.05) and procalcitonin (r=0.504, P<0.05). The prognosis of patients treated with surgery (26/28) was better than that of patients without surgery (0/8) (P<0.01). Conclusions: The patients with maxillofacial and cervical multi-space infection combined with DNM might be in critical condition. The surgical based MDT strategy has an important impact on the prognosis of patients. White blood cell count and other inflammatory indicators monitoring can effectively observe the changes of the patient's condition.

[Clinical features and imaging analysis of primary bone lymphoma of the jaw].

Objective: To investigate the clinical characteristics and imaging manifestations of primary bone lymphoma (PBL) located in the jaw. Methods: Clinical data of 14 PBL patients admitted to The First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019 were retrospectively analyzed, which including age, gender, location, chief complaint, laboratory test, imaging manifestations and so on. Results: Among the 14 PBL patients, 10 were male and 4 were female. Age range from 4 to 79 years, median age was 56 years old. There were 6 cases involved maxillary, 7 cases involved mandible and 1 case involved mandible and maxillary simultaneously. Twelve patients were admitted with local mass as the chief complaint, 3 had a history of toothache, 4 had loosen tooth and 2 had numbness of lips and cheeks. Two cases of oral mass with mucosal surface ulcer or abscess formation. One case complained of fever, night sweats and other systemic symptoms. The imaging findings showed 8 cases of osteolytic lesions, 1 case of sclerosis, 4 cases of mixed lesions and 1 case of cystic lesions. One case had periosteum reaction. In 12 cases, there was an obvious mass, which was characterized by the large soft-tissue mass and marrow changes were associated with surprisingly little cortical destruction. Conclusions: PBL is more common in middle aged male. The upper and lower jaw bones can be involved. Clinical and imaging manifestations lack characteristics, and common dental or periodontal symptoms such as toothache, tooth loosening, and paresthesia may occur. However, the imaging characteristics of large soft tissue masses with small degree of bone destruction can be used as an important basis for the differential diagnosis of osteomyelitis, squamous cell carcinoma, osteosarcoma and other diseases.

[Clinical strategies for preservation of the exposed implant in chronic wounds and wound repair].

Objective: To explore the clinical strategies for preservation of the exposed implant in chronic wounds and wound repair. Methods: From January 2016 to January 2019, totally 8 patients (4 males and 4 females, aged 10 to 73 years) sustaining postoperative chronic wounds with exposed implants were admitted to the Fourth Medical Center of PLA General Hospital. There were 2 cases of abdominal patch exposure after abdominal trauma surgery, 2 cases of titanium plate exposure post craniocerebral surgery, 3 cases of internal fixator exposure post orthopedic surgery, and 1 case of cerebrospinal fluid drainage tube exposure after craniocerebral surgery. The wound exudate was collected for bacterial culture on admission. On the basis of glycemic control and correction of anemia and hypoproteinemia, thorough wound debridement was performed as soon as possible and the wound area after debridement ranged from 2.0 cm×0.5 cm to 6.0 cm×5.0 cm. The wounds of 4 patients were immediately closed after debridement, including 1 case by primary closure, 1 case by primary closure after local filling of platelet rich plasma gel, and 2 cases by local flap transplantation, with flap size of 10.0 cm×8.0 cm and 12.0 cm×8.0 cm, respectively. The donor sites of flaps were sutured directly and all the incisions were treated with continuous vacuum sealing drainage (VSD) after surgery. The other 4 patients were treated with continuous VSD after debridement to improve the wound bed. The wound of 1 case healed gradually, 1 case received direct wound suturing, and the wounds of 2 cases were repaired with thin split-thickness skin grafts from the thigh or the head. The results of bacterial culture of wound exudate on admission, wound healing post surgery, and follow-up were observed and recorded. Results: The bacterial culture of wound exudate on admission was positive in 6 patients, and 10 strains of bacteria were isolated with Staphylococcus epidermidis as the main pathogen. All the skin grafts or flaps of patients survived post surgery, with the incisions and wounds healed and all the implants preserved. After 1 to 3 years of follow-up, no recurrence of wound was found in any patient. Conclusions: The postoperative chronic wounds with exposed implants can be closed in primary stage by direct suturing or flap transplantation if it is clean enough on the basis of thorough debridement. The wounds with large defects or serious infection can be treated with continuous VSD firstly and then closed with direct suturing or skin grafting for delayed wound closure, thereby to reach the treatment goal of preserving the implants and repairing the wounds simultaneously.

[Preliminary study on the elimination of artifacts of five kinds of dental prosthetic materials by energy spectrum CT multi-material artifact reduction technology].

Objective: To investigate the effect of the multi-material artifact reduction (MMAR) algorithm of spectral CT in reducing the beam hardening artifacts in dental restoration material. Methods: Three-unit fixed bridge restorations were fabricated on the first to third molars in pig jaw. Gold alloy, zirconia, cobalt chromium alloy, nickel chromium alloy and pure titanium were used as materials for these fixed bridges. After restoration delivery, the pig jaw was scaned using energy spectrum CT machines. Images in regular 120 kVp scan mode were used as conventional group, and reconstructed single-energy horizontal images of 80, 90, 100, 110, 120, 130 and 140 keV in energy spectrum scanning mode were used as energy spectrum group, and reconstructed images applied MMAR technology in energy spectrum scanning mode were used as energy spectrum MMAR group. Each group was scanned 10 times to measure CT value and noise of muscles around dental prosthetic materials and adjacent non-artifact layers. Artifact index was calculated. Two radiologists scored the image quality of each group subjectively. Kruskal Wallis rank sum test was used to compare the difference of image noise, artifact index and subjective score among the control group and the best keV condition in the energy spectrum group and the energy spectrum MMAR group. Results: The image noise of energy spectrum group and energy spectrum MMAR group decreased gradually with the increase of single energy level. The artifact index of pure titanium restorations in conventional group, energy spectrum group and energy spectrum MMAR group were 71.0±8.0, 21.4±2.7 and 14.7±2.7 respectively, and these values were significantly lower than those of other materials in the same group (P<0.05). The subjective image quality scores in energy spectrum MMAR group were as follows: 3.0±0.2 for gold alloy, 4.3±0.5 for zirconia, 3.0±0.4 for cobalt chromium alloy, 3.1±0.4 for cobalt chromium alloy, and 4.6±0.5 for pure titanium. These scores were significantly smaller than those in the conventional group (P<0.05). There was no significant difference in noise between energy spectrum group and energy spectrum MMAR group (P>0.05), and the noise values in energy spectrum group and energy spectrum MMAR group were significantly lower than that in the conventional group (P<0.05). Conclusions: Artifacts of pure titanium is minimal. Energy spectrum CT combined with MMAR technology can effectively reduce the artifacts of gold, zirconia, cobalt-chromium alloy, nickel-titanium alloy and pure titanium. This technique can be used as an effective method to remove artifacts of dental prosthesis.

LncRNA SNHG1 inhibits neuronal apoptosis in cerebral infarction rats through PI3K/Akt signaling pathway.

OBJECTIVE: To investigate the effects of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 1 (SNHG1) on the neuronal apoptosis in rats with cerebral infarction through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats were divided into M group (model control group), N group (rat model of cerebral infarction) and R group (rat model of cerebral infarction plus lncRNA SNHG1) and then treated accordingly. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was applied to detect the percentage of cerebral infarct volume and apoptosis of brain cells in the three groups of rats; hematoxylin and eosin (HE) staining was utilized to observe the pathological morphology of brain tissues, and Western blotting was performed to measure the protein levels of phosphorylated PI3K (p-PI3K) and p-Akt in the brain tissues. RESULTS: The degree of neurological deficit in the N group was much higher than that in the M group (p<0.05), and it was decreased markedly in the R group compared with that in the N group, with statistically significant differences (p<0.05). In comparison with that in the M group, the cell apoptosis was aggravated notably in the N group and alleviated remarkably in the R group, and the differences were statistically significant (p<0.05). In the N group, the cerebral infarct volume accounted for 33.67% of the whole brain volume, and mild cerebral infarction was detected in the R group, with a percentage of cerebral infarct volume of 20.15%. N group had a more prominent increase in the cerebral infarct volume than the R group (p<0.05). Compared with those in the M group, the pyknotic nuclei and neuron staining of brain tissues were increased significantly, and the neuronal cell injury was aggravated in the N group, while markedly reduced pyknotic nuclei and neuron staining (p<0.05), as well as mild neuronal cell injury (p<0.05), were detected in the R group. The levels of p-PI3K and p-Akt proteins in the brain tissues declined remarkably in the N group compared with those in the R group (p<0.05). CONCLUSIONS: The protective effect of lncRNA SNHG1 on the rats with cerebral infarction is correlated with the activation of the PI3K/Akt signaling pathway.

Correlations of acute myocardial infarction complicated by cerebral infarction with insulin resistance, adiponectin and HMGB1.

OBJECTIVE: To investigate the correlations of acute myocardial infarction (AMI) complicated by cerebral infarction with insulin resistance, adiponectin and high-mobility group box 1 (HMGB1). PATIENTS AND METHODS: A total of 326 AMI patients receiving percutaneous coronary intervention (PCI) were selected as the research objects. They were divided into cerebral infarction group (n=24) and non-cerebral infarction group (n=302) based on their complication of cerebral infarction. In addition, 165 healthy people were enrolled as control group. Changes in the levels of HMGB1, adiponectin, fasting insulin (FINS), insulin sensitive index (ISI), insulin resistance, N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), interleukin-6 (IL-6), myocardial infarction markers and coagulation function indexes were compared among the three groups. Correlations among those indexes were analyzed. RESULTS: AMI patients had higher levels of HMGB1, FINS, homeostasis model assessment of insulin resistance (HOMA-IR), ISI, creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), prothrombin time (PT), CRP and IL-6 than those in healthy participates, especially in those complicated with cerebral infarction. Conversely, levels of adiponectin, myoglobin (Mb), activated partial thromboplastin time (APTT), antithrombin III (AT-III), activated coagulation time (ACT) and NT-proBNP were the lowest in cerebral infarction group, and highest in control group (p<0.05). AMI complicated with cerebral infarction was negatively correlated with the levels of AT-III and adiponectin, but positively associated with the levels of NT-proBNP, HOMA-IR and HMGB1 (p<0.05). CONCLUSIONS: AMI complicated with cerebral infarction has negative correlations with the levels of AT-III and adiponectin, but positively associated with the levels of NT-proBNP, HOMA-IR and HMGB1, possessing certain clinical significance in AMI treatment.

Superconductivity in a unique type of copper oxide.

The mechanism of superconductivity in cuprates remains one of the big challenges of condensed matter physics. High-T c cuprates crystallize into a layered perovskite structure featuring copper oxygen octahedral coordination. Due to the Jahn Teller effect in combination with the strong static Coulomb interaction, the octahedra in high-T c cuprates are elongated along the c axis, leading to a 3dx 2-y 2 orbital at the top of the band structure wherein the doped holes reside. This scenario gives rise to 2D characteristics in high-T c cuprates that favor d-wave pairing symmetry. Here, we report superconductivity in a cuprate Ba2CuO4-y , wherein the local octahedron is in a very exceptional compressed version. The Ba2CuO4-y compound was synthesized at high pressure at high temperatures and shows bulk superconductivity with critical temperature (T c ) above 70 K at ambient conditions. This superconducting transition temperature is more than 30 K higher than the T c for the isostructural counterparts based on classical La2CuO4 X-ray absorption measurements indicate the heavily doped nature of the Ba2CuO4-y superconductor. In compressed octahedron, the 3d3z 2-r 2 orbital will be lifted above the 3dx 2-y 2 orbital, leading to significant 3D nature in addition to the conventional 3dx 2-y 2 orbital. This work sheds important light on advancing our comprehensive understanding of the superconducting mechanism of high T c in cuprate materials.

Li(Cd,Mn)P: a new cadmium based diluted ferromagnetic semiconductor with independent spin & charge doping.

We report a new diluted ferromagnetic semiconductor Li1+y(Cd,Mn)P, wherein carrier is doped via excess Li while spin is doped by isovalence substitution of Mn2+ into Cd2+. The extended Cd 4d-orbitals lead to more itinerant characters of Li1+y(Cd,Mn)P than that of analogous Li1+y(Zn,Mn)P. A higher Curie temperature of 45 K than that for Li1+y(Zn,Mn)P is obtained in Li1+y(Cd,Mn)P polycrystalline samples by Arrott plot technique. The p-type carriers are determined by Hall effect measurements. The first principle calculations and X-ray diffraction measurements indicate that occupation of excess Li is at Cd sites rather than the interstitial site. Consequently holes are doped by excess Li substitution. More interestingly Li1+y(Cd,Mn)P shows a very low coercive field (<100 Oe) and giant negative magnetoresistance (~80%) in ferromagnetic state that will benefit potential spintronics applications.

MicroRNA-19a-3p suppresses invasion and metastasis of prostate cancer via inhibiting SOX4.

OBJECTIVE: To explore the role of microRNA-19a-3p in regulating invasion, metastasis and EMT (epithelial mesenchymal transition) of prostate cancer (PCa) cells, as well as its underlying mechanism. MATERIALS AND METHODS: MicroRNA-19a-3p mimic and negative control plasmid were first constructed. After transfection of microRNA-19a-3p mimic or negative control in DU145 cells, expression levels of microRNA-19a-3p and SOX4 were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and Western blot. The regulatory effects of microRNA-19a-3p on migration and invasion of DU145 cells were detected by wound healing assay and transwell assay, respectively. Protein levels of matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), N-cadherin, Vimentin, alpha-smooth muscle actin (α-SMA) and E-cadherin in DU145 cells transfected with microRNA-19a-3p mimic or negative control were detected by Western blot. RESULTS: Overexpression of microRNA-19a-3p inhibited protein level of SOX4 in DU145 cells. The migration and invasion of DU145 cells were inhibited after transfection of microRNA-19a-3p mimic. Protein levels of MMP2, MMP9, N-cadherin, Vimentin and α-SMA were downregulated, whereas E-cadherin was upregulated after microRNA-19a-3p overexpression. CONCLUSIONS: MicroRNA-19a-3p inhibits migration, invasion and EMT of PCa cells via inhibiting SOX4.

[Effect of human trophoblast cell-surface antigen 2 gene expression by RNA interference on proliferation and apoptosis of tongue squamous cell carcinoma and its mechanism].

Objective: To investigate the effect and its mechanism of human trophoblast cell-surface antigen 2 (Trop2) gene expression was inhibited in squamous cell carcinoma of tongue on the proliferation and apoptosis of cancer cells. Methods: A total of 46 patients from February 2014 to May 2016 received radical treatment of tongue cancer from oral and maxillofacial surgery of the First Affiliated Hospital of Zhengzhou University were enrolled in this study. Real time PCR and Western blotting were used to detect mRNA and protein expression of Trop2 in tongue squamous cell carcinoma and corresponding adjacent tissues; NC-siRNA and Trop2-siRNA were transfected into human tongue squamous cell carcinoma CAL-27 cells, a blank control group (control) was set, the expression of Trop2, Ki-67, cyclin D1, cleaved caspase3, Notch1, Hes1 protein after transfected for 48 h were detected by Western bloting; cell proliferation was detected by cell counting kit-8; cell cycle and apoptosis rate were detected by flow cytometry. Results: The mRNA (5.72±1.13) and protein expression (0.77±0.06) of Trop2 gene in tongue squamous cell carcinoma were significantly higher than those in adjacent tissues (0.92±0.15, 0.11±0.01, P<0.05); Trop2 protein expression after transfeced Trop2-siRNA (0.08±0.01) in CAL-27 cells decreased significantly (0.46±0.05); the survival rate (64.28±4.12)%, S cells (14.54±1.02)% and Ki-67 (0.12±0.01), cyclin D1 (0.04±0.01) protein expression in Trop2-siRNA group were significantly lower than those in control group [(100.00±1.02)%, (27.33±1.11)%, (0.24±0.02), (0.20±0.02)] and NC-siRNA group [(96.55±2.43)%, (26.67±1.23)%, (0.26±0.03), (0.21±0.024)], the apoptosis rate (23.55±1.45)%, G0/G1 cells (72.32±0.94)% and the expression of cleaved caspase 3 (0.16±0.02), Notch1 (0.62±0.06) and Hes1 (0.50±0.05) protein were significantly higher than control group and NC-siRNA group (P<0.05). Conclusions: The expression of Trop2 gene was inhibited in tongue squamous carcinoma cells can reduce the proliferation of cancer cells, block the cells in phase G1, and promote the apoptosis of cells. The mechanism is related to the up regulation of Notch1 signaling pathway.

Clinical significance and levels of blood brain natriuretic peptides in patients with persistent atrial fibrillation before and after catheter ablation.

The aim of this study was to observe levels of blood brain natriuretic peptides (BNPs) in patients with persistent atrial fibril-lation (AF) before and after catheter ablation. Thirty-six patients with persistent AF (28 successful surgeries and eight recurrent cases) and 36 healthy controls with normal sinus rhythm were recruited for this study. BNP levels in the AF and control groups were measured before and after catheter ablation. BNP levels before surgery were significantly higher in the persistent AF group than in the control group (P < 0.01). The successful surgery group had distinctly lower BNP levels before ablation than the recurrent group (P < 0.01). In the recurrent group, BNP levels 2 h after ablation were significantly lower than those be-fore ablation (P < 0.01); these levels increased after AF recurrence (P < 0.01) and were comparable with those before ablation (P < 0.01). Logistic regression analysis indicated that the BNP level was an inde-pendent factor for and predictor of AF recurrence (P < 0.01). The BNP level in patients with persistent AF is clinically important in predicting and evaluating AF recurrence after ablation.

Safety and efficacy of intracoronary tirofiban administration in patients with serious thrombus burden and ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

OBJECTIVE: This work aims to explore the safety and efficacy of intracoronary tirofiban administration in patients with serious thrombus burden and ST-elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 104 patients with serious thrombus burden and acute STEMI were randomly divided into treatment (intracoronary tirofiban administration, 56 cases) and control (48 cases) groups. Comparison of coronary blood flow, ST-segment resolution (STR), duration of hospital stay, 30-day major adverse cardiac events (MACE) and complications such as hemorrhage was conducted. RESULTS: In treatment group, the percentage of thrombolysis in myocardial infarction-3 (TIMI-3) flow in the infarct-related artery (IRA) increased (89.3% to 85.4, p < 0.05), blood flow in the IRA calculated with TIMI frame count method enhanced [(1.68 ± 0.23) ml/s to (1.42 ± 0.31) ml/s, p < 0.05], STR on electrocardiogram (ECG) enlarged [(64.3 ± 7.84)% to (48.6 ± 6.47)%, p < 0.05)] and the prevalence of MACE decreased (10.7% to 18.8%, p < 0.05), all of which were significantly different from those of control group, but no statistical difference in complications was observed between two groups (p > 0.05). CONCLUSIONS: It was simple, safe and effective to perform intracoronary tirofiban administration in patients with serious thrombus burden and STEMI when undergoing emergency PCI.

Polymorphism of the OLR1 3'UTR potential microRNA binding site and risk of Alzheimer's disease: a meta-analysis.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that contributes to dementia in the elderly population. Genome-wide linkage analysis has identified chromosome 12p as the AD-susceptible region, which includes lectin-like oxidized low-density lipoprotein receptor 1 (OLR1). The OLR1 +1073 C/T single-nucleotide polymorphism is located in the 3'-untranslated region of the gene and may influence the binding of regulatory microRNAs (miRNAs) and OLR1 protein homeostasis. A number of studies have reported an association between this variant and AD. However, the results are controversial. A meta-analysis of case-control studies examining the relationship between the OLR1 +1073 C/T single-nucleotide polymorphism and AD risk was performed. Five studies were selected that included 2419 cases and 2381 controls. The results revealed a significantly decreased AD risk in the recessive model (TT vs TC + CC: odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.65-0.96). The control group in one of the studies was in Hardy-Weinberg disequilibrium, so we performed additional meta-analysis excluding this study. The significance was much more pronounced in the recessive model (TT vs TC + CC: OR = 0.72, 95%CI = 0.62-0.85). Using miRanda and RNA hybrid methods, the polymorphic allele was shown to influence the binding of various miRNAs. Our results suggested that the +1073 C/T polymorphism decreased the risk of AD. The polymorphic allele was also predicted to affect the binding site of many miRNAs, which may explain the relationship between the +1073 C/T variant and AD.

The essential role of transient receptor potential vanilloid 1 in simvastatin-induced activation of endothelial nitric oxide synthase and angiogenesis.

AIMS: We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin-mediated activation of endothelial nitric oxide synthase (eNOS) and angiogenesis. METHODS: Fluo-8 NW assay was for Ca(2+) detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis. RESULTS: In endothelial cells (ECs), treatment with simvastatin time-dependently increased intracellular level of Ca(2+). Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin-mediated elevation of intracellular Ca(2+) in ECs or TRPV1-transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin-induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin-elicited increase in the formation of TRPV1-Akt-CaMKII-AMPK-eNOS complex. In mice, Matrigel plug assay showed that simvastatin-evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin-activated TRPV1-Ca(2+) signalling and in the consequent NO production and angiogenesis as evidence by that re-expression of TRPA1 further augmented simvastatin-elicited Ca(2+) influx in TRPV1-expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin-induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1-Akt-CaMKII-AMPK-eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice. CONCLUSION: Simvastatin-induced Ca(2+) influx may through the activation of TRPV1-TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1-CaMKII-AMPK-eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs.

Activation of soluble guanylyl cyclase prevents foam cell formation and atherosclerosis.

AIMS: Soluble guanylyl cyclase (sGC) is a key modulator in the regulation of vascular tone. However, its role and involving mechanism in cholesterol metabolism of macrophages and atherosclerosis remain unclear. METHODS: Oil red O staining, Dil-oxidized low-density lipoprotein (oxLDL)-binding assay and cholesterol efflux assay were performed in biology of foam cells. Levels of cytokines or intracellular lipid were evaluated by ELISA or colorimetric kits. Expression of gene or protein was determined by quantitative real-time PCR or Western blotting. Histopathology was examined by haematoxylin and eosin staining. RESULTS: Soluble guanylyl cyclase was expressed in macrophages of mouse atherosclerotic lesions. Treatment with 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, sGC inhibitor) exacerbated oxLDL-induced cholesterol accumulation in macrophages. In contrast, 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1, sGC activator) attenuated the oxLDL-induced cholesterol accumulation because of increased cholesterol efflux. Additionally, YC-1 dose dependently increased the protein expression of ATP-binding cassette transporter A1 (ABCA1) but did not alter that of scavenger receptor class A (SR-A), CD36, SR-BI or ABCG1. Moreover, YC-1-upregulated ABCA1 level depended on liver X receptor α (LXRα). Inhibition of the LXRα-ABCA1 pathway by LXRα small interfering RNA (siRNA), ABCA1 neutralizing antibody or ABCA1 siRNA abolished the effect of YC-1 on cholesterol accumulation and cholesterol efflux. In vivo, YC-1 retarded the development of atherosclerosis, accompanied by reduced serum levels of cholesterol and pro-inflammatory cytokines, in apolipoprotein E-deficient mice. CONCLUSION: Activation of sGC by YC-1 leads to LXRα-dependent upregulation of ABCA1 in macrophages and may confer protection against atherosclerosis.