Influence of recombinant human B-type natriuretic peptide on improving ventricular function in patients with ST elevation myocardial infarction.

OBJECTIVE: The aim of this study was to investigate the effect of recombinant human B-type natriuretic peptide (rhBNP) on improving ventricular function in patients with ST-elevation myocardial infarction (STEMI). PATIENTS AND METHODS: In this retrospective study, 96 patients with STEMI admitted to Cangzhou Central Hospital from June 2017 to June 2019 were recruited and randomized to either a control group or an experimental group, with 48 patients in each group. Patients in both groups were given conventional pharmacological therapy, and an emergency coronary intervention was performed within 12 hours. Patients in the experimental group received rhBNP intravenously postoperatively, whereas patients in the control group received an equal amount of 0.9% NaCl solution through an intravenous drip. Postoperative recovery indicators were compared between the two groups. RESULTS: Patients treated with rhBNP showed better postoperative respiratory frequency, heart rate, blood oxygen saturation, pleural effusion, acute left heart remodeling after surgery and central venous pressure at 1-3 days after surgery than those without (p<0.05). Early diastolic blood flow velocity/early diastolic motion velocity (E/Em) and wall-motion score indices (WMSI) of patients in the experimental group were markedly lower compared to the control group one week after surgery (p<0.05). Patients receiving rhBNP had better left ventricular ejection fraction (LVEF) and WMSI six months after surgery and higher left ventricular end diastolic volume (LVEDV) and LVEF one week after surgery than the controls (p<0.05). Administration of rhBNP for patients with STMI provided a higher treatment safety by significantly reducing the incidence of left ventricular remodeling and complication than conventional medication (p<0.05). CONCLUSIONS: Intervention with rhBNP in STEMI patients could effectively inhibit ventricular remodeling, alleviate symptoms, reduce adverse complications and improve ventricular function.

Selenylation to charge transfer improvement at the counter electrode (CE)/electrolyte interface for nanocrystalline Cu1.8S1-xSex CEs.

Pt counter electrodes (CEs) have been widely used in dye-sensitized solar cells (DSSCs) due to their high conductivity and electrocatalytic activity. However, industrialization of DSSCs is limited by shortcomings of Pt CEs such as being expensive, and weak corrosion resistance in electrolytes. Reported in this paper is two simple approaches to Pt-free Cu1.8S1-xSex CEs. Nanocrystalline Cu1.8S1-xSex CEs were fabricated via two processes, that is, a solvothermal process to Cu1.8S1-xSex powder followed by CE fabrication, and a solvothermal process and CE fabrication to Cu1.8S films followed by selenylation to Cu1.8S1-xSex CEs. Photoelectric conversion efficiencies (PCE) of 4.02% and 4.16% were achieved respectively by the as-fabricated Cu1.8S1-xSex CEs. Compared with the cells with Cu1.8S CEs fabricated by the same processes, increases of 19% and 45% were achieved, respectively. The PCE improvement comes from the enhancement of charge transfer at the CE/electrolyte interface induced by the selenylation of the CEs.

[CacyBP promotes the proliferation and invasion of non-small cell lung cancer].

Objective: To investigate the effects and the mechanism of Calcyclin-binding protein (CacyBP) on the proliferation and invasion of non-small cell lung cancer (NSCLC) cells. Methods: Six lung cancer tissues and paired normal lung tissues were collected from NSCLC patients who underwent surgical treatment in Jinan Central Hospital during 2016. The expression of CacyBP in these tissues was examined by western blot. The protein and mRNA expression of CacyBP in human bronchial epithelial cells (16HBE), NSCLC cell lines including A549, H1299, H460 and H1975 were examined by western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RNAi and shRNA against negative control (NC) or CacyBP were transfected into A549 cell which were denoted as siNC group, siCacyBP-1 group, sicacyBP-2 group, shNC group and shCacyBP group, respectively. Control and Flag-CacyBP plasmids were transfected into A549 cells which were denoted as NC group and Flag-CacyBP group, respectively. Cell counting kit-8 (CCK-8), plate clone formation assay and flow cytometry assay were used to assess cell proliferation ability and cycle of A549. Wound healing assay and transwell assay were used to assess abilities of A549 cells migration and invasion. The protein expressions of epithelial-mesenchymal transition (EMT) markers including E-cadherin, N-cadherin, Snail1, Vimentin, and phosphorylation of protein kinase B (p-Akt) were examined in CacyBP depleted or overexpressed A549 cells. Results: The CacyBP protein level in NSCLC tissues was 0.41±0.23, significantly higher than 0.11±0.04 in normal lung tissues (P<0.05). The CacyBP protein expression levels in different NSCLC cell lines including A549, H1299, H460 and H1975 were 0.35±0.01, 0.38±0.01, 0.32±0.01 and 0.41±0.01, respectively, which were significantly higher than 0.03±0.01 in 16HBE cells (P<0.05). The result of RT-PCR was consistent with that of western blot. Compared with siNC group (absorbance was 1.54±0.03), siCacyBP-1 group and siCacyBP-2 group showed decreased cell proliferation (absorbances were 1.38±0.04 and 1.34±0.03, P<0.05). The number of cell colony in shNC group was 41.33±3.21, significantly higher than 22.00±3.61 in shCacyBP group (P<0.05). The proportion of G(1) phase in shCacyBP group was (61.35±5.45)%, higher than (49.61±1.54) % in shNC group (P<0.05). The proportion of S phase was (25.41±3.21)%, which was lower than (38.68±0.46)% of shNC group (P<0.05). The cell migration rate of shCacyBP group was (12.67±0.71)%, which was significantly lower than (35.50±2.07)% of shNC group (P<0.05). The numbers of cell migration and invasion in shNC group were 406.33±7.37 and 92.33±8.50, respectively, which were significantly higher than 224.67±10.01 and 66.00±7.94 in shCacyBP group (P<0.05). Compared with siNC group, the expression of epithelial marker E-cadherin was up-regulated, while the expressions of mesenchymal markers including N-cadherin, Vimentin, Snail1 and p-Akt were down-regulated in CacyBP depleted A549 cells. Compared with NC group, overexpression of CacyBP inhibited E-cadherin expression while promoted the expressions of N-cadherin, Snail1, Vimentin and p-Akt, which could be restored by LY294002. Conclusion: CacyBP may promote the proliferation and invasion of NSCLC cells by regulating Akt signal pathway.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.

[Clinical application of mCIM and eCIM combined detection of carbapenemase-producing enterobacteriaceae].

Objective: To explore the clinical application value of modified carbapenem inactivation test (mCIM) combined with EDTA-modified carbapenem inactivation test (eCIM) for detecting the carbapenemase of CRE isolated from infected patients in clinical diagnosis and infection control of CRE infection. Methods: Drug resistance of seventy eight non-repetitive enterobacteriaceae resistant to carbapenem antibiotics, which were isolated from clinically infected patients from January 2017 to December 2017 in the Tianjin Medical University General Hospital, was retrospectively analyzed. Meanwhile, Vitek2 Compact automatic bacterial identification instrument was used to identify the species and detect its minimum inhibitory concentration (MIC) for ertapenem and imipenem. Carbapenemase genes blaKPC, blaNDM, blaIMP and blaVIM were detected by PCR test, the genotype was determined by gene sequencing as the gold standard, and mCIM Combined eCIM test was used for carbapenemase detection of collected bacteria. Using PCR results as the standard, the sensitivity, specificity, positive predictive value, negative predictive value and Cohen' Kappa value of mCIM and eCIM were calculated, and the consistency of the combined detection results of mCIM and eCIM and PCR results was checked. Results: Seventy eight carbapenem-resistant Enterobacteriaceae were detected by PCR, 74 carbapenemase gene positive and 4 negative, including 60 blaKPC-2 positive, 2 blaNDM-1 positive and blaNDM-5 positive Of the 7 strains, 3 strains were positive for blaNDM-9, 1 strain was positive for blaIMP-4, and 1 strain was both positive for blaKPC-2 and blaNDM-1. The sensitivity of mCIM to detect carbapenemase is 100%, the specificity is 100%, and the Kappa value is 1.000; the combined detection of mCIM and eCIM for serine carbapenemase has a sensitivity of 100%, the specificity is 100%, and the Kappa value is 1.000; The sensitivity of combined detection of metallo-ß-lactamase is 92.9%, the specificity is 100%, and the Kappa value is 0.955. Conclusions: The combined test of mCIM and eCIM which is used to detect carbapenemase in CRE costs low, doesn't require special reagents and equipment, has strong practicability, simple operation, and easy interpretation of results. According to the different genotypes of CRE bacteria, it provides important clinical diagnostic evidence for clinical CRE diagnosis, precise antimicrobial treatment and infection control.

Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism.

OBJECTIVE: Pulmonary embolism (PE) is a primary clinical manifestation of venous thromboembolism (VTE). It has been demonstrated that pulmonary endothelial cells (PECs) are apoptotic-resistant in PE. MATERIALS AND METHODS: In this study, PECs were collected from PE patients and mouse models. Western blot, RT-PCR, flow cytometry, H&E and TUNEL assay, confocal and TEM microscopy, and Luciferase reporter assay were performed to determine the effects of miR-28-3p on PECs apoptosis and if exosomes can act as the shuttle to transport miR-28-3p to PECs. RESULTS: The results revealed that apoptosis and miR-28-3p were downregulated in PECs of PE. The miR-28-3p mimics and inhibitor enhanced and further inhibited apoptosis in PECs, respectively. Both miR-28-3p-modified adipose tissue-derived mesenchymal stem cells (AMSCs) and AMSC-derived exosomes upregulated miR-28-3p expression in PECs, leading to elevated apoptosis of PECs. Apoptosis inhibitor 5 (API5) was a direct target gene of miR-28-3p, and the overexpression of API5 in miR-28-3p-modified PECs further suppressed apoptosis. Furthermore, the administration of miR-28-3p-modified exosomes to PE mouse model promoted apoptosis in PECs. CONCLUSIONS: Exosomal miR-28-3p could ameliorate PE-associated apoptosis-resistance in PECs through targeting API5 in vitro and in vivo. Therefore, AMSCs-derived exosome is a promising way to deliver functioning miRNA to PECs, providing insight into novel therapy of PE.

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial.

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

[Investigation on the content of persistent organic pollutants in fish from Dongting Lake in China].

Objective: To investigate the content of persistent organic pollutants (POPs) in fish from Dongting Lake. Methods: Ten sample collection points were set in lakeside city Yueyang and Yuanjiang. In July (wet season) and November (dry season) of 2012, 13 common fish species were captured by convenience sampling in Dongting Lake. Two to three fish with similar weight were selected in each season for the same species of fish. After sample preparation and pretreatment, the contents of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), indicator polychlorinated biphenyls and polybrominated diphenyls ether (PBDEs) in the samples were determined by high resolution gas chromatographer-high resolution mass spectrometry. Toxicity Equivalents (TEQ) of PCDD/Fs and dl-PCBs were calculated according to the revised toxicity equivalent factor (TEF) of WHO in 2005. The contents of POPs were expressed by median and quavtile. The differences of POPs in fish in different periods were compared by Wilcoxon rank sum test. Results: The content of PCDD/Fs of fish in Dongting Lake in wet season was 12.397 (8.865, 24.964) pg/g, higher than that in the dry season 0.771 (0.490, 1.442) pg/g (P<0.001), and the toxicity equivalent quantity (TEQ) were 0.150 (0.066,0.528) and 0.143 (0.066, 0.235) pg-TEQ/g without statistically significant difference (P>0.05). For the fish in wet and dry season from Dongting Lake,Σdl-PCBs of fish were 66.475 (28.065, 77.794) and 24.205 (18.237, 90.777) pg/g, respectively, and the TEQ were 0.061 (0.046, 0.268) and 0.075 (0.054, 0.182) pg-TEQ/g; Σ indicative PCBs were 237.764 (153.896, 335.483) and 119.711 (52.171, 408.696) pg/g, respectively; Σ PBDEs were 106.513 (64.834, 164.860) and 86.837 (61.872, 177.108) pg/g, respectively. The highest content of PCDD/Fs was found in grass carp (198.360 pg/g) in wet season. The higher content of PCBs was found in long-necked fish (2 332.509 pg/g) and PBDEs was found in pelteobagrus fulvidraco (343.857 pg/g), respectively. Conclusion: A lower burden was found in fishes from Dongting Lake, and the content of POPs varied in different seasons and fishes.

Measurement of the cosmic ray proton spectrum from 40 GeV to 100 TeV with the DAMPE satellite.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

HCP5 promotes colon cancer development by activating AP1G1 via PI3K/AKT pathway.

OBJECTIVE: To explore whether HCP5 participates in the pathogenic progression of colon cancer (CC) and its underlying mechanism. PATIENTS AND METHODS: HCP5 expression in CC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the HCP5 expression and tumor stage of CC patients was then analyzed. After CC cells were transfected with HCP5-siRNA, the proliferation and migration capacities were detected by cell counting kit-8 (CCK-8), colony formation and transwell assay, respectively. Cell cycle was examined by flow cytometry. Western blot was conducted to detect protein expressions of HCP5, AP1G1 and relative molecules in the PI3K/AKT pathway. Rescue experiments were performed by co-transfection of HCP5-siRNA and AP1G1-siRNA into CC cells, followed by cell function detection. RESULTS: HCP5 was highly expressed, whereas AP1G1 was lowly expressed in CC tissues and cell lines. Besides, CC patients with stage III-IV presented higher expression of HCP5 than those with stage I-II. The knockdown of HCP5 in CC cells down-regulated proliferation and migration capacities, and arrested cell cycle in the G0/G1 phase, which was reversed by the AP1G1 knockdown. In addition, HCP5 knockdown up-regulated AP1G1 expression, whereas down-regulated the expression of relative proteins in the PI3K/AKT pathway. CONCLUSIONS: HCP5 was significantly increased in CC and enhanced the proliferation and migration of CC cells by inhibiting the AP1G1 expression. HCP5 promoted CC development by activating the PI3K/AKT pathway.

[Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review].

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) . Methods: Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed. Results: The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months. Conclusions: Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.

[Operative strategy and clinical results of complex four part distal radius fractures by combined palmar and dorsal internal fixation].

Objective: To explore a standard procedure for the treatment of combined dorsal and palmar internal fixation for complex four part distal radius fractures and assess its clinical results. Methods: From May 2009 to October 2016, 38 patients(39 sides)who suffered from complex four part distal radius fractures were performed operatively with open reduction and internal fixation via combined dorsal and palmar approach in Department of Orthopaedic Trauma, Qilu Hospital of Shandong University(Qingdao). The series included 22 males(22 sides) and 16 females(17 sides). Age of the patients was 53.5 years ranging from 25 to 79 years.According to Melone classification, there were 34 sides of type of Ⅳ, 5 of type Ⅴ.According to Frykman classification, there were 15 sides of type Ⅶ, 24 sides of type Ⅷ, and all the cases were type C3 according to AO/OTA classification.Preoperatively, the key articular fragments in four part distal radius fractures were identified and the individual fracture patterns from conventional X-ray and CT-scan were analyzed. All the patients were performed combined volar and dorsal fixation.Firstly, a palmar approach which gave access to and fix the palmar-ulnar fragment and the radial styloid fragment was performed.Then a limited dorsal approach across the third extensor compartment which gave access to the dorso-ulnar fragment and a limited dorsal arthrotomy to visualize the radiocarpal joint when necessary were performed.Through dorsal approach, we can address the dorso-ulnar fragment, free intra-articular fragment and direct visualize the joint.Use of a retinacular flap was routinely advocated to help prevent against tendon irritation and rupture.The follow-up control included conventional X-ray, range of motion(ROM), grip strength, and the disabilities of the arm, shoulder and hand index(DASH), as well as the patient-rated wrist evaluation(PRWE) score for functional outcome at 6 and 12 months. Results: Thirty-three patients(34 sides) were followed up for at least 12 months.The would healed well in all cases 2 weeks postoperatively, and no soft tissue infections, necrosis or neurovascular complications occurred.All the fractures of 38 cases(39 sides)healed averaged 3.6 months(ranging from 2.5-5.7 months), and no loss of reduction occurred postoperatively.Anatomic reconstruction with a step or gap of <1 mm was achieved in 37 cases(38 sides), Whereas 5 patients were lost to follow-up at 12 months postoperatively.ROM and grip strength were all recovered to over 85% of the unaffected side(exception of the bilateral patient). Median DASH-index and PRWE were 6.5(0-17) and 9.3(0-20)respectively. Conclusion: Combined volar and dorsal approaches allow achieving anatomic reconstruction in complex four part intra-articular distal radius fractures and reveal good functional outcomes at intermediate follow-up.

Mechanism of feedback regulation of neutrophil inflammation in Henoch-Schönlein purpura.

OBJECTIVE: The aim of this study is to investigate the role of complement-neutrophil feedback regulation of inflammatory response in Henoch-Schönlein purpura (HSP) through constructing an animal model of HSP. MATERIALS AND METHODS: Twenty-four SPF grade Japanese large-eared white rabbits were randomly divided into normal group and model group, 12 for each group. HSP model was constructed by challenging rabbits with gastric gavage of a decoction solution containing ginger, Piper longum L. and pepper, intraperitoneal injection of ovalbumin (OVA)-Freund's adjuvant and intravenous injection at marginal ear vein and subcutaneous injection in the back of rabbits with OVA normal saline solution. Changes in general conditions of rabbits including food intake, water intake and body temperature as well as alterations in blood routine, urine routine, reactive oxygen species (ROS), inflammatory cytokines and complement were compared between two groups. In the meantime, N-Acetyl-L-Cysteine (NAC)and hydrogen peroxide (H2O2) treatment was used to manipulate ROS level and determined the changes in aforementioned parameters. RESULTS: After sensitization, rabbits of the model group displayed significantly elevated body temperature, apathy, reduced physical activity, significantly decreased water and food intake compared to the situations before sensitization (p<0.05). Significant pathological changes were observed in these rabbits through HE staining study. Furthermore, blood levels of white blood cells (WBC), mean corpuscular hemoglobin concentration (MCHC), neutrophils (NEU) and NEU% were significantly increased, whereas levels of red blood cells (RBC), hemoglobin (HGB), eosinophils (EOS) and EOS% were significantly decreased (p<0.05). No significant alterations were observed in levels of mean corpuscular hemoglobin (MCH) and platelet (PLT) (p>0.05). Urine with mucus and a strong odor was observed in model rabbits. Proteinuria occurred in 66.67% of model rabbits, hematuria in 58.33% and presence of WBC in the urine in 25%. Also, levels of ROS, inflammatory cytokines, tumor growth factor (TGF)-ß, complement and tumor necrosis factor (TNF)-α were significantly increased in model rabbits. After the treatment of ROS inhibitor, NAC, levels of these parameters were significantly decreased (p<0.05), but significantly increased after treatment of H2O2, the ROS agonist (p<0.05). CONCLUSIONS: Complement-neutrophil feedback regulation of inflammatory response plays important roles in the pathogenesis of HSP, and inhibition of ROS can suppress the development and progression of HSP.

Uptake characteristics of levofloxacin for the eradication of Helicobacter pylori by GES-1 and MGC80-3 cells.

OBJECTIVE: The aim of this study was to study the uptake of levofloxacin for the eradication of Helicobacter pylori by human gastric epithelial cell lines, GES-1 and MGC80-3. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) and coomassie brilliant blue staining, among other methods, were used to study the uptake of levofloxacin in GES-1 and MGC80-3 cells. The effect of time, concentration, temperature, pH, cyclosporine A, verapamil, and cimetidine on uptake was analyzed. RESULTS: The uptake of levofloxacin by GES-1 and MGC80-3 cells reached a steady state after 15 minutes of incubation, and was enhanced by increasing the extracellular levofloxacin concentration, although not in a linear manner. A maximum uptake was observed at 37 °C and pH 7.4. Cyclosporin A and verapamil enhanced uptake in GES-1 cells by 2.07%-13.23% (p > 0.05), and 17.5%-35.3% in MGC80-3 cells (p < 0.05). The uptake of levofloxacin was not affected by cimetidine. CONCLUSIONS: P-glycoprotein mediates levofloxacin uptake in MGC80-3 cell. Further, P-glycoprotein may be involved in levofloxacin uptake in GES-1 cells. However, organic cation transporters were not involved in levofloxacin uptake in MGC80-3 and GES-1 cells.

Minimally invasive manipulative reduction with poking k-wire fixation in the treatment of various types of calcaneal fractures.

OBJECTIVE: The aim of this study is to investigate the safety and clinical efficacy of minimally invasive manipulative reduction with poking k-wire fixation in the treatment of various types of calcaneal fractures. PATIENTS AND METHODS: Between July 2012 and July 2014, a prospective parallel controlled study was conducted on 96 patients with closed calcaneal fractures who were admitted to our institution. These patients were randomly divided into two groups, with 48 in each group. Patients in plate group were treated using open reduction and internal fixation, whereas those of manipulation group were treated with minimally invasive manipulative reduction with poking k-wire fixation. All patients were followed up for six months to assess the postoperative recovery and complications. Kerr's scale was adopted to evaluate the functional recovery of fractured calcaneus. RESULTS: A mean healing duration of 9.48 ± 1.92 weeks was achieved in patients of plate group compared with a healing duration of 9.35 ± 1.66 weeks in those of manipulation group, with no statistical significance (p > 0.05). Complications occurred in 20 cases in plate group versus in seven cases in manipulation group with significant difference (p < 0.05). As for Sanders type II fracture, among patients with compression fracture and tongue type fracture, > 70% of patients achieved with excellent and good outcomes in both groups with no significant difference in clinical efficacy (p > 0.05). The rate of excellent and good outcomes in Sanders type III compression fractures was lower in manipulation group than in plate group (p < 0.05). As for Sanders type II fractures, the Kerr's score of tongue type fractures in manipulation group was higher than that in plate group, and comparison within manipulation group showed that the score of tongue type fractures was significantly higher than that of compression fractures (p < 0.05). However, as for Sanders type III fractures, the score of tongue type fractures in manipulation group was significantly higher than that in plate group, and the score of compression fractures in plate group was significantly higher than that in manipulation group (p < 0.05). CONCLUSIONS: Minimally invasive manipulative reduction with poking k-wire fixation is suitable for the treatment of Sanders type II tongue type and compression calcaneal fractures, as well as the treatment of Sanders type III tongue type fractures with several advantages, including easy operation, lower cost, fewer complications and favorable recovery.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells.

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Primary lymphoepithelioma-like carcinoma of ocular adnexa: clinicopathologic features and treatment.

BACKGROUND AND METHODS: Lymphoepithelioma-like carcinoma (lelc) is a rare malignancy in ocular adnexa. Here, we report 4 patients with lelc and review 11 patients reported in the literature. Clinical profiles, association with Epstein-Barr virus (ebv), treatment, and outcomes are analyzed. RESULTS: Lacrimal glands and the lacrimal drainage system, eyelid, and conjunctiva are potential primary sites for lelc. The tumours are characterized histologically by nests of undifferentiated malignant cells surrounded by lymphoid infiltrates. Infection with ebv was confirmed in lelc of ocular adnexa, and that association seemed to be restricted to Asian populations. Results from our centre uniformly showed expression of ebv-encoded small rnas in primary tumour, locally recurrent tumour, and metastatic lymph nodes. This disease had a tendency to relapse regionally. Postoperative radiotherapy seems to improve disease-free survival. Tumours appear to be sensitive to radiotherapy and chemotherapy based on cisplatin and 5-fluorouracil. At our centre, 3 patients were still living at 22, 33, and 76 months after surgery. One patient died of distant metastasis after a survival of 38 months. CONCLUSIONS: Lymphoepithelioma-like carcinoma is a heterogenous entity among ocular adnexal malignancies. Multimodality treatment provides a better chance at survival. Further investigation is required to achieve a better understanding of the biologic behavior of this entity and of its optimal treatment.

Molecular analysis and frequency of Staphylococcus aureus virulence genes isolated from bloodstream infections in a teaching hospital in Tianjin, China.

Staphylococcus aureus is an important cause of bloodstream infections worldwide. We examined the prevalence of genes that encode erythromycin ribosome methylase and bacterial toxins in S. aureus collected from bloodstream infections. Sixty different S. aureus isolates were obtained from blood cultures of patients who were admitted to a Teaching Hospital in Tianjin from January 2006 to August 2011. The susceptibility of the isolates to 16 antibiotics was tested. Methicillin-resistant S. aureus (MRSA) was identified using the disk diffusion method with cefoxitin. PCR was used to detect genes that encode the staphylococcal enterotoxins, Panton-Valentine leukocidin, toxic shock syndrome toxin 1 and erythromycin ribosome methylase. Molecular analysis of the MRSA strains was done using pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome mec (SCCmec) typing. The positivity rates of mecA, ermA, ermB, and ermC in the isolates were 13/60, 10/60, 18/60, and 18/60, respectively. Among the 60 isolates, 30 harbored enterotoxin genes, with sea as the most frequent toxin gene (33%), followed by sec (15%), sed (12%), and seb (5%). The see and tst genes were not found in any of the isolates. The pvl gene was detected in four strains. Eleven MRSA isolates were of the SCCmec type III; two MRSA isolates could not be determined through SCCmec typing. PFGE analysis of the 13 MRSA isolates produced 8 distinct pulsotypes. Virulence genes and erythromycin ribosome methylase genes were highly prevalent in these isolates. The PFGE results demonstrated that the MRSA spread through cloning, mainly involving SCCmec type III.