Avian influenza A virus continues to pose a global threat with occasional H5N1 human infections, which is emphasized by a recent severe human infection caused by avian-origin H7N9 in China. Luckily these viruses do not transmit efficiently in human populations. With a few amino acid substitutions of the hemagglutinin H5 protein in the laboratory, two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model. Here in this study one of the mutant H5 proteins developed by Kawaoka's group (VN1203mut) was expressed in a baculovirus system and its receptor-binding properties were assessed. We herein show that the VN1203mut had a dramatically reduced binding affinity for the avian α2,3-linkage receptor compared to wild type but showed no detectable increase in affinity for the human α2,6-linkage receptor, using Surface Plasmon Resonance techonology. Further, the crystal structures of the VN1203mut and its complexes with either human or avian receptors demonstrate that the VN1203mut binds the human receptor in the same binding manner (cis conformation) as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses. Our receptor binding and crystallographic data shown here further confirm that the ability to bind the avian receptor has to decrease for a higher human receptor binding affinity. As the Q226L substitution is shown important for obtaining human receptor binding, we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.
Air Microbiology ; Crystallography, X-Ray ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; metabolism ; Humans ; Influenza A Virus, H5N1 Subtype ; chemistry ; metabolism ; Influenza A Virus, H7N9 Subtype ; chemistry ; Models, Molecular ; Mutant Proteins ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Stability ; Receptors, Cell Surface ; genetics ; metabolism ; Solubility ; Surface Plasmon Resonance ; Temperature

OBJECTIVETo explore the sensitivity and accuracy of CT and HRCT in early detection of coal-worker's pneumoconiosis (CWP) associated micronodules, nodule coalescence and emphysema from coal miners with and without radiographic CWP evidence.

METHODContinuously Thorax-Vol. CT scanning and High resolution CT scanning were performed on 113 coal miners with or without radiographic CWP evidence and 37 health controls by the use of Multi Spiral Computed Tomography (MSCT). The CT and HRCT images were evaluated for lung parenchyma opacity profusion category, nodule coalescence, emphysema index and mean lung attenuation, and then compared with that on radiographs.

RESULTGood agreement for CWP associated opacity profusion grading was achieved between radiographs and CT scans (Kappa = 0.771). The sensitivity of CT and HRCT were 98.70% for CWP diagnosis when compared with radiographs. 8 (22.22%) cases out of 36 radiographic CWP negative coal miners were categorized as grade 1 opacity profusion in consistent with CWP on CT and HRCT scans, and 26 (35.62%) cases out of 73 radiographic grade 1-2 CWP patients were detected to have at least grade 3 nodular profusion on CT and HRCT scans. Among 113 coal miners, 36 (31.86%) were recognized as emphysema positive on CT; whereas only 7 (6.19%) on radiographs. According to CT opacity profusion grading, mean lung attenuation in coal miners with grade 1-2 opacity profusion classification was significantly increased than that in health control, CWP negative coal miner and grade 4 opacity profusion groups (F1 = -45.73, F2 = -23.00 and F3 = 52.72, P < 0.01 and P < 0.05).

CONCLUSIONCT and HRCT acquired from MSCT showed high sensitive and accurate for the early detection of micronodules, nodule coalescence and emphysema in coal miners. It could be used as semi-quantitative and quantitative method in early diagnosis of CWP and its complications.

Adult ; Aged ; Anthracosis ; diagnostic imaging ; Case-Control Studies ; Early Diagnosis ; Humans ; Lung ; diagnostic imaging ; Male ; Middle Aged ; Pulmonary Emphysema ; diagnostic imaging ; Sensitivity and Specificity ; Tomography, Spiral Computed ; Tomography, X-Ray Computed ; methods

Influenza virus is the causative agent of the seasonal and occasional pandemic flu. The current H1N1 influenza pandemic, announced by the WHO in June 2009, is highly contagious and responsible for global economic losses and fatalities. Although the H1N1 gene segments have three origins in terms of host species, the virus has been named swine-origin influenza virus (S-OIV) due to a predominant swine origin. 2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many aspects. Hemagglutinin is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of infection. Primary sequence analysis of the 2009 S-OIV hemagglutinin (HA) reveals its closest relationship to that of the 1918 pandemic influenza virus, however, analysis at the structural level is necessary to critically assess the functional significance. In this report, we report the crystal structure of soluble hemagglutinin H1 (09H1) at 2.9 Å, illustrating that the 09H1 is very similar to the 1918 pandemic HA (18H1) in overall structure and the structural modules, including the five defined antiboby (Ab)-binding epitopes. Our results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV, and people born around the 1918 are resistant to the current pandemic, yet younger generations are more susceptible to the 2009 pandemic.
Animals ; Cloning, Molecular ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; immunology ; isolation & purification ; Influenza A Virus, H1N1 Subtype ; chemistry ; genetics ; immunology ; Models, Molecular ; Protein Conformation ; Swine ; virology

ObjectiveTo investigate the possible mechanism of Bushen Zhuyun prescription （BSZYP） to reduce the level of ovarian apoptosis in Brown Norway （BN） rats with luteal phase deficiency （LPD）. MethodFifty SPF female BN rats were randomly divided into a model group， a dydrogesterone group （0.002 g·kg^-1）， and a low （4.5 g·kg^-1）， a medium （9 g·kg^-1）， and a high-dose （18 g·kg^-1） BSZYP groups， with ten rats in each group. The rats were administrated with corresponding drugs by gavage， once a day for three estrus cycle. Western blot was used to detected the protein expression levels of c-Jun NH2 terminal kinase （JNK）， extracellular signal-regulated kinase （ERK）， phosphorylated-ERK （p-ERK）， phosphorylated-JNK （p-JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylated-p38 MAPK （p-p38 MAPK ）， B-cell lymphoma （Bcl-2）， and Bcl-2 associated X protein （Bax） in ovary. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of ERK， JNK， p38 MAPK， Bax， and Bcl-2 in ovary. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E₂） levels. Hematoxylin-eosin （HE） staining was used to observe the ovarian tissue morphology. ResultCompared with the model group， the recovery of estrus cycle of rats in all BSZYP groups had statistical significance after 1-circle administration （P<0.05）. The ovarian tissue morphology in the low-dose BSZYP group was improved， and that in the medium and high-dose BSZYP groups was significantly improved with clear follicle， less vesicular follicle and atretic follicle， and more granular layers. The number of luteum， especially the fresh luteum， in the medium and high-dose groups was increased with smooth edge and large volume. The mRNA expression level of Bcl-2 was increased in all-dose BSZYP groups， while the mRNA expression level of Bax was significantly decreased in all-dose BSZYP group （P<0.05， P<0.01）. The mRNA expression levels of JNK and p38 MAPK were significantly decreased in the high-dose BSZYP group （P<0.01）， and the mRNA expression levels of ERK were increased in the low and medium-dose BSZYP groups （P<0.05）. The protein expression level of Bcl-2 was significantly increased in the medium and high-dose BSZYP groups （P<0.01）， and the protein expression level of Bax was significantly decreased in the all-dose BSZYP groups （P<0.01）. No significant difference was observed in the protein expressions of JNK， ERK， and p38 MAPK in the BSZYP groups. The protein expression levels of p-ERK in the ovarian tissues of rats were significantly inoreased in the medium and high-dose BSZYP group （P<0.01）， p-JNK， and p-p38 MAPK in the ovarian tissues of rats were significantly decreased in the medium and high-dose BSZYP group （P<0.01）. The level of E₂ was increased in all-dose BSZYP groups （P<0.05， P<0.01）， and the level of P in the medium-dose BSZYP group was increased （P<0.05）. ConclusionBSZYP improved the serum sex hormones， restored the estrous cycle， reduced atretic follicle and vesiculation， and maintained luteal morphology and function of BN rats， so as to improve luteal function and treat luteal phase deficiency. The mechanism of BSZYP may be related to reduce the level of ovarian tissue apoptosis in BN rats by regulating MAPKs signaling pathway.

Heart failure is a common frequently-occurring disease, and it is the terminal stage of the development of various heart diseases. The pathogenesis is very complex and seriously endangers human health. A large number of studies have shown that Ca2+/Calmodulin dependent protein kinase II(CaMKII) plays an important role in the occurrence and development of heart failure. Traditional Chinese medicine has unique advantages and good prospects in the prevention and treatment of heart failure. Among them, there are many compound and their active ingredients can target and regulate CaMKII. This paper mainly expounds the mechanism of the CaMKII signaling pathway in the failing heart and the research progress of traditional Chinese medicine in preventing and treating heart failure by targeting the regulation of CaMKII signaling in recent years, in order to provide reference and expand ideas for clinical traditional Chinese medicine prevention and treatment in heart failure.

Objective: To study the feasibility, safety and short-term efficacy of total laparoscopic rectal cancer surgery with transanal natural orifice specimen extraction and resection. Methods: From May 2014 to March 2016, 17 patients with rectal carcinoma were treated by total laparoscopic rectal cancer surgery with transanal natural orifice specimen extraction and resection. The clinical data of these patients was collected and retrospectively analyzed to assess the impact of the operation on postoperative recovery time and the incidence of complications. Results: All operations had been successfully accomplished without conversion to open surgery or conversional laparoscopic-assisted surgery . The median operative time was 105 minutes. The median blood loss was 35 ml. The median proximal and distal margin of tumor is 16 cm and 3.5 cm. The median number of lymph nodes harvest is 21, and the median first bowl movement is 43 hours. The hospitalization after operation is 8 days. No patient underwent abdomen hemorrhage or anastomotic leakage. Conclusion Laparoscopic rectal cancer surgery with transanal natural orifice specimen extraction and resection appears to be feasible, safe and with promising efficacy for selected patients.

Objective: To investigate the safety and feasibility of laparoscopic remedial surgery in patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. Methods: The clinical and follow-up data of 12 patients who didn′t reach the cure criterion of early colorectal cancer and then underwent endoscopic resection was collected. The clinicalpathological features and remedial indications were analyzed to evaluate the effects of laparoscopic remedial surgery. Results: The average number of lymph nodes in the lymph node dissection was 15 during remedial surgery, and 3 of them had lymph node metastasis. Among the 3 patients with residual cancer, two cases were poorly differentiated, 1 case was moderately differentiated, 1 case was positive for basal margin, and 1 case had vascular invasion. No lymph node metastasis occurred in the 9 patients who had no residual cancer. Among these, 8 cases were moderately differentiated, 1 case was poorly differentiated and 2 cases had positive basal margin. The average follow-up duration was 40 months and all 12 patients were in a state of survival at the last follow-up. During the follow-up of the 3 patients with residual cancer, 1 patient received adjuvant chemotherapy with unknown prognosis; 1 patient received postoperative adjuvant radiochemotherapy, and lung metastasis occurred; 1 patient did not receive any treatment after surgery and survived for 33 months. Conclusions Laparoscopic remedial surgery is a safe and feasible remedy for patients who didn′t reach the cure criterion of early colorectal cancer after endoscopic resection. However, the choice of remedial strategy for colorectal carcinoma needs further investigation for patients with no vascular invasion, high degree of differentiation, and negative basal margin.

BACKGROUNDThe emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.

METHODSThis prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.

RESULTSThe median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.

CONCLUSIONSSubstantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.