A novel fluffy PLGA/HA composite scaffold for bone defect repair.

Treatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, the present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. Transplant of fluffy PLGA/HA composite scaffold in a rabbit model showed a significant increase in mineralized tissue production compared to conventional and fluffy PLGA/HA composite scaffold. These findings are promising for fluffy PLGA/HA composite scaffolds used in bone defects.

Clinical features and diagnostic approaches for abdominal tuberculosis: five-year experience from a non-tuberculosis-designated hospital in China.

BACKGROUND AND PURPOSE: abdominal tuberculosis (TB) is a common form of extrapulmonary TB but it is still a diagnostic dilemma in clinical practice. This study aimed to highlight the clinical features and diagnostic approaches for abdominal TB. METHODS: seventy cases of diagnosed abdominal TB were retrospectively collected between August 1st, 2015 and June 30th, 2020. They were classified as peritoneal TB, lymph node TB, gastrointestinal TB, visceral TB or mixed TB. RESULTS: eighteen patients were diagnosed with peritoneal TB, nine with lymph node TB, five with gastrointestinal TB, two with visceral TB and 36 with mixed TB. More than 65 % of the patients had tuberculosis of other sites except the abdomen. The median diagnosis time was 60 days. Ascites (58.6 %), abdominal distension (48.6 %), weight loss (44.3 %) and fever (42.9 %) were the most common symptoms. The overall microbiological and histological detection rates were 70.0 % and 38.6 %, respectively. The non-ascite samples yielded a higher microbiological confirmation rate (63.6 %) than the total samples (40.8 %). Diagnosis was confirmed histologically in 18 patients (69.2 %). Forty-five cases (64.3 %) were clinically diagnosed. Invasive procedures such as surgery (6/7), percutaneous biopsy (7/7) and endoscopy in lymph node TB (4/5) had high confirmation rates. CONCLUSIONS: the diagnosis of abdominal TB should be reached by a combination of clinical, laboratory, radiological, microbiological and pathological findings.

A Photoluminescent Cd(II) Coordination Polymer with Potential Active Sites Exhibiting Multiresponsive Fluorescence Sensing for Trace Amounts of NACs and Fe3+ and Al3+ Ions.

The elaborately designed π-electron-rich fluorescent ligand 1,4-bis(1-carboxymethylene-4-imidazolyl)benzene (H2L), possessing bifunctional groups including the carboxylate groups (building units) and 4-imidazoyl groups (N-donor potential active sites) has been employed to construct fluorescent coordination polymers. A luminescent sensor, namely [Cd(L)(phen)2]·5H2O (1), was obtained, which has a one-dimensional structure. The fluorescent material shows a blue emission maximum at 457 nm with a luminescence lifetime of 488 ns and a quantum yield (QY) of 4.56%. Significantly, 1 serves as a promising multiresponsive luminescent sensor to detect trace nitroaromatic compounds (NACs) with the limits of detection (LOD) of 7.21 × 10-8, 1.85 × 10-5, and 1.15 × 10-5 mol/L for 2-nitrophenol (2-NP), 3-nitrophenol (3-NP), and 4-nitrophenol (4-NP), respectively. Furthermore, CP 1 exhibits fluorescent turn-off and turn-on sensing behavior for Fe3+ and Al3+ metal ions with trace amounts of 1.05 × 10-7 and 1.13 × 10-7 mol/L, respectively. Experimental methods and theoretical calculations were employed to elucidate the sensing mechanism in detail.

Features of Ebola Virus Disease at the Late Outbreak Stage in Sierra Leone: Clinical, Virological, Immunological, and Evolutionary Analyses.

We performed Ebola virus disease diagnosis and viral load estimation for Ebola cases in Sierra Leone during the late stage of the 2014-2015 outbreak (January-March 2015) and analyzed antibody and cytokine levels and the viral genome sequences. Ebola virus disease was confirmed in 86 of 1001 (9.7%) patients, with an overall case fatality rate of 46.8%. Fatal cases exhibited significantly higher levels of viral loads, cytokines, and chemokines at late stages of infection versus early stage compared with survivors. The viruses converged in a new clade within sublineage 3.2.4, which had a significantly lower case fatality rate.

A novel reassortant H2N3 influenza virus isolated from China.

OBJECTIVE: To analyze the genetic composition of a novel H2N3 virus isolate identified from a duck cage swab in a live poultry market (LPM) in 2009 in Guangdong province of China. METHODS: PCR-positive specimens were inoculated into embryonated chicken eggs and subtyped by conventional RT-PCR. All segments of the virus A/environment/Guangdong/2/2009 were sequenced, and phylogenetic trees were constructed and analyzed. RESULTS: The genes of this virus belong to Eurasian-lineage avian viruses. The virus is a reassortant with the HA gene from an H2N2 virus and the NA gene from an H5N3 virus. The PB1, PB2, and NP genes were from an H4N6 virus, the PA was from an H3N8 virus, the M gene was from an H1N3 virus, and the NS gene was from an H10N6 virus. CONCLUSION: A novel avian-origin reassortant H2N3 influenza virus was detected in a live poultry market. Its potential impacts and evolution should be closely monitored.

H5N1 Avian Influenza Pre-pandemic Vaccine Strains in China.

OBJECTIVE: To prepare the 4 candidate vaccine strains of H5N1 avian influenza virus isolated in China. METHODS: Recombinant viruses were rescued using reverse genetics. Neuraminidase (NA) and hemagglutinin (HA) segments of the A/Xinjiang/1/2006, A/Guangxi/1/2009, A/Hubei/1/2010, and A/Guangdong/1/2011 viruses were amplified by RT-PCR. Multibasic amino acid cleavage site of HA was removed and ligated into the pCIpolI vector for virus rescue. The recombinant viruses were evaluated by trypsin dependent assays. Their embryonate survival and antigenicity were compared with those of the respective wild-type viruses. RESULTS: The 4 recombinant viruses showed similar antigenicity compared with wild-type viruses, chicken embryo survival and trypsin-dependent characteristics. CONCLUSION: The 4 recombinant viruses rescued using reverse genetics meet the criteria for classification of low pathogenic avian influenza strains, thus supporting the use of them for the development of seeds and production of pre-pandemic vaccines.

R229I substitution from oseltamivir induction in HA1 region significantly increased the fitness of a H7N9 virus bearing NA 292K.

The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was high. These drug-resistant strains showed good replication capacity without serious loss of fitness. In the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. Pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased (1) replication ability in MDCK(P < 0.05) and A549(P < 0.05), (2) neuraminidase enzyme activity, (3) binding ability to both α2,3 and α2,6 receptor, (4) pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), (5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titre). It indicated that through the fine-tuning of HA-NA balance, R229I increased the fitness and changed the antigenicity of H7N9 virus bearing NA 292K. Public health attention to this mechanism needs to be drawn.

A novel reassortant H3N8 influenza virus isolated from drinking water for duck in a domestic duck farm in Poyang Lake area.

OBJECTIVE: To conduct a full genome sequence analysis for genetic characterization of an H3N8 influenza virus isolated from drinking water of a domestic duck farm in Poyang Lake area in 2011. METHODS: The virus was cultivated by specific pathogen free (SPF) chicken embryo eggs and was subtyped into hemagglutinin (HA) and neuraminidase (NA) by real-time PCR method. Eight gene segments were sequenced and phylogenetic analysis was conducted. RESULTS: The NA gene of this virus belongs to North American lineage; other seven genes belong to Eurasian lineage. Compared with the viruses containing NA gene, the PB2 and PB1 gene came from different clades. And this indicates that the virus was a novel reassortant genotype. The HA receptor binding preference was avian-like and the cleavage site sequence showed a low pathogenic feature. There was no drug resistance mutation of M2 protein. The mutations of Asn30Asp, and Thr215Ala of the M1 protein implied the potential of pathogenicity increase in mice. CONCLUSION: The finding of novel genotype of H3N8 virus in drinking water in this duck farm near Poyang Lake highlighted the importance of strengthening the surveillance of avian influenza in this region, which could contribute to pinpointing the influenza ecological relations among avian, swine, and human.

2,3-Dibromo-6-meth-oxy-4-[(phenethyl-amino)-methyl-idene]cyclo-hexa-2,5-dien-1-one methanol monosolvate.

In the title compound, C(16)H(15)Br(2)NO(2)·CH(4)O, the mean planes of the substituted cyclo-hexa-2,5-dien-1-one and phenyl rings are almost parallel [dihedral angle = 7.84 (4)°]. The crystal packing is stabilized by N-H⋯O hydrogen bonds generating infinite [101] chains. The methanol solvent mol-ecules are connected with the main species by O-H⋯O inter-actions.

[Interventional effects of different management programs on the outcomes of stable chronic obstructive pulmonary disease patients].

OBJECTIVE: To evaluate the interventional effects of different management programs on the outcomes of stable chronic obstructive pulmonary disease (COPD) patients. METHODS: Systemic education, follow-up and control groups were divided according to the frequency of follow-ups and the profile of participating in education. A total of 157 patients were enrolled into the COPD database from May 2002 to May 2010. They were interviewed face-to-face at our department. The investigation contained general conditions, the frequency of acute exacerbations (AE) the previous year, COPD Assessment Test (CAT), Modified British Medical Research Council Dyspnea Scale (mMRC) and spirometric classification. A combined assessment was conducted. RESULTS: The frequency of AE and rate of AE < once the previous year in systemic education group was 0.9 ± 1.1 and 71.2%, 1.0 ± 0.8 and 68.6% in follow-up group and 1.4 ± 1.1 and 44.4% in control group. And the frequency of AE in systemic education and follow-up groups was significantly less than that in control group (P < 0.05). Rate of AE < once in systemic education and follow-up groups was significantly higher than that in control group (P < 0.01). CAT and rate of CAT ≤ 20 in systemic education, follow-up and control groups were 10.0 ± 5.0 and 96.2%, 11.1 ± 6.0 and 88.2%, 15.3 ± 6.8 and 64.8% respectively. CAT in systemic education and follow-up groups was significantly lower than that in control group (P < 0.01). Rate of CAT ≤ 20 in systemic education and follow-up groups was significantly higher than that in control group (P < 0.01). mMRC in systemic education, follow-up and control groups was 1.5 ± 0.8, 1.6 ± 0.9 and 2.1 ± 1.0 respectively. mMRC in systemic education and follow-up groups was significantly lower than that in control group (P < 0.05). Combined assessment showed that no significant difference existed in Types A and B among three groups (P > 0.05). Type C in the systemic education group was significantly higher than that of the control (P < 0.05). Type D in the systemic education and follow-up groups was significantly lower than that of the control (P < 0.01). CONCLUSION: Long-term systemic education and follow-up management program can reduce the frequency of AE of COPD effectively and improve the health status of COPD patients.

The Epidemiological Pattern and Co-infection of Influenza A and B by Surveillance Network From 2009 to 2014 in Anhui Province, China.

Influenza-like illness (ILI) is one of the most important public health problems globally, causing an enormous disease burden. Influenza infections are the most common cause of ILI. Bacterial and virus co-infection is common yet the data of co-infection with influenza A and B viruses are scarce. To identify the epidemiological patterns of and co-infection of influenza A and B in Anhui province, China, we analyzed the surveillance data of 5 years from 2009 to 2014 collected by the Chinese National influenzas network. The results showed that the weekly ratio of ILI was 3.96 ± 1.9% (95% CI 3.73-4.2%) in outpatients and the highest affected population was children under 5 years old. The epidemic of influenza viruses was highest during 2009-2010. For the other 4 surveillance years, school-aged people (5-14 years) were the most highly affected population. Influenza B and H3N2 viruses were more prevalent than H1N1pdm09 virus after 2010. In addition, a significant co-circulation of influenza A (H1N1pdm09 and H3N2) and influenza B virus was detected with 0.057% PCR positive rate during 2009-2014 in Eastern China, yet isolated only in pediatric patients. Our data reveals school-aged population would be the main vulnerable population and a distinct seasonality for influenza. In addition, the co-infection of influenza A and B were found in Anhui Province, China. Ongoing surveillance is critical to understand the seasonality variation and make evidence-based vaccination recommendations. Information on the epidemiological patterns and co-infections of influenza A and B can help us to implement different strategies for selecting vaccine formulations and monitoring new emerging influenza strains. In addition, the identification of the susceptible population can help us to develop more precise protection measures.

N-[(E)-4-(Methyl-sulfon-yl)benzyl-idene]-3-nitro-aniline.

In the title compound, C(14)H(12)N(2)O(4)S, the dihedral angle between the two aromatic rings is 35.65 (12)°. The crystal packing is stabilized by weak C-H⋯O hydrogen bonds and aromatic π-π ring stacking inter-actions [minimum ring centroid separation = 3.697 (3) Å].

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice.

OBJECTIVE: Interferon-induced transmembrane protein 3 (IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo. METHODS: We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer (NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/- and wild-type mice. RESULTS: Ifitm3-/- mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/- mice during acute influenza infection. CONCLUSIONS: Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/- mice.

[Evaluation of chronic obstructive pulmonary disease screening in a high risk population].

OBJECTIVE: To investigate the results of spirometry testing used in the screening of COPD from at risk populations. METHODS: A survey of the population aged over 40 years with any of chronic cough and sputum, dyspnea, heavy tobacco smoke was performed, using a questionnaire on clinical characteristics of COPD. Spirometry and chest X ray examination were performed. Different screening methods were compared for sensitivity and specificity for COPD diagnosis. RESULTS: Of 241 surveyed persons, 156 were diagnosed as having COPD, among whom 126 cases were firstly diagnosed. Among all surveyed persons, 87 (36. 1%) cases had mild and moderate COPD, while 69 (28. 6%) had severe and very severe disease. The sensitivity and specificity for diagnosis of COPD of shortness of breath were 61.5% and 61.2% respectively. Combination of respiratory symptoms and risk factors improved the screening power. More than 40 years of age combined with any of heavy smoking, chronic cough and sputum, or shortness of breath, improved the sensitivity to more than 90 percent. CONCLUSIONS: Spirometry test screening of the at risk population can effectively improve early diagnosis of COPD.

miR-590-3p is a novel microRNA which suppresses osteosarcoma progression by targeting SOX9.

Osteosarcoma is the most common primary bone malignancy and arises primarily in the metaphyseal ends of long bones in children and adolescents. m iR-590 has been found to have anti-tumor effects in many other cancers. However, the role of miR-590-3p in osteosarcoma is poorly understood. In this study, we show that miR-590-3p was significantly decreased both in osteosarcoma tissues and cell lines, suggesting a potential role of miR-590-3p in osteosarcoma. Over-expression of miR-590-3p inhibited U2OS cell viability as shown by the CCK-8 assay and clonogenic assay. Ki-67 immunofluorescence staining and cell cycle analysis revealed that up-regulation of miR-590-3p inhibited U2OS cell proliferation. Transfection with miR-590-3p mimics suppressed PCNA, Cyclin D1 and CDK4 expression and increased p53 and p21 expression. In addition, U2OS cells transfected with miR-590-3p mimics exhibited reduced cell invasion and migration, characterized by the wound healing assay and transwell assay. Furthermore, bioinformatics analysis demonstrated that SOX9 was a potential target of miR-590-3p. SOX9 was up-regulated in osteosarcoma tissues. Transfection with miR-590-3p mimics markedly suppressed SOX9 expression both at the mRNA level and protein level. Dual luciferase assay validated the direct binding site of miR-590-3p on SOX9. Exogenous SOX9 expression in U2OS cells at least partially reversed the effects of miR-590-3p in U2OS cells. Enforced SOX9 expression restored cell viability in osteosarcoma cells transfected with miR-590-3p mimics. In addition, over-expression of SOX9 restored decreased cell metastasis properties caused by transfection with miR-590-3p mimics in osteosarcoma cells. In summary, these results indicated that miR-590-3p is an anti-cancer miRNA that can inhibit proliferation and metastasis in osteosarcoma cells. Our findings provide a novel insight into the biological function of miR-590-3p in osteosarcoma and SOX9 may be a potential therapeutic target for osteosarcoma.

Study of 3-bromopyruvate on regulating imbalance of apoptosis/autophagy in fibroblast-like synoviocytes through AMPK/mTOR pathway / 中国药理学通报

Aim To investigate the regulatory effects of 3-bromopyruvate (3-BrPA) on apoptosis and autophagy of fibroblast-like synoviocytes (FLS) in rats based on AMPK/mTOR signaling pathway and the underlying mechanism. Methods FLS of rats in vitro were cultured and induced by tumor necrosis factor-α (TNF-α) to construct a model of rheumatoid arthritis (R A). MTT assay was used to explore the optimal concentration of TNF-α and 3 -BrPA for induction and treatment of FLS. The effects of 3-BrPA on the migration and invasion of FLS were detected by Wound healing assay and Transwell assay. The apoptosis of FLS was tested by flow cytometry and mitochondrial membrane potential assay kit (JC-1). Moreover, FLS autophagic flux was detected by mCherry-EGFP-LC3B-overexpressed plasmids, and the expression of apoptosis/autophagy-related proteins as well as AMPK/mTOR pathway-related proteins were detected by Western blot. Results 3-BrPA (15 μmol • L) significantly inhibited the proliferation, migration, and invasion of FLS stimulated by TNF-a (25 μg • L

[Respiration control dysfunction and the relationship to sleep-disordered breathing in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To analyze the polysomnographic (PSG) features of sleep apnea hypopnea syndrome (SAHS) in patients with chronic obstructive pulmonary disease (COPD), and to define the association between SAHS and respiratory control disorder. METHODS: Three hundred patients with stable COPD were screened for SAHS using questionnaire, Epworth sleep scale (ESS) and home pulse oximeter testing. Those with ESS > or = 10 or oxygen desaturation over 3% more than 5 times per hour sleep were under further PSG testing. The PSG features were compared between COPD patients with apnea hypopnea index (AHI) > 10 and 118 SAHS patients with normal lung function. The two groups were matched for age, body mass index (BMI) and AHI. Among them 22 with COPD and AHI > or = 10 were tested for the chemo-responsiveness to isocapnic hypoxia and hypercapnia. RESULTS: Among the 300 patients with stable COPD, 79 had AHI over 10, meeting the diagnostic criteria of overlap syndrome (OS). Analysis of the polysomnography found that 32 cases (40%) with OS had more hypoventilation lasting over 1 min during sleep. Compared to patients with SAHS only, OS patients had higher percentage of hypopnea index over AHI [(69 +/- 30)% vs (52 +/- 31)%] and a higher percentage of total hypopnea time over total time of sleep apnea and hypopnea [(15 +/- 12)% vs (12 +/- 10)%]. OS patients also had lower hypoxic [(-0.11 +/- 0.05) vs (-0.35 +/- 0.24) L.min(-1).%(-1)] and hypercapnic responses [(1.1 +/- 0.8) vs (1.6 +/- 0.8) L.min(-1).mm Hg(-1) (1 mm Hg = 0.133 kPa)]. CONCLUSION: Patients with both COPD and SAHS had more episodes of hypopnea and hypoventilation during sleep, and had depressed chemo-responsiveness to hypoxia during wakefulness.

In situ reduction of silver nanoparticles by chitosan-l-glutamic acid/hyaluronic acid: Enhancing antimicrobial and wound-healing activity.

Spongy composites with silver nanoparticles (AgNPs) were synthesized by freeze-drying a mixture of silver nitrate (AgNO3) and chitosan-l-glutamic acid (CG) derivative loaded with hyaluronic acid (HA) solution. CG/AgNP spongy composites had an interconnected porous structure and rough surfaces. When AgNPs (5-20nm) were immobilized on these spongy composites, AgNP aggregation was dependent on AgNO3 concentration. The spongy composites exhibited good mechanical properties, swelling, and water retention capacity. In vitro antibacterial activity showed that the CG/AgNP spongy composites effectively inhibited bacterial (Escherichia coli and Staphylococcus aureus) growth and penetration. Spongy composites containing low concentrations of AgNP were non-toxic to L929 cells, while CG/HA/AgNP spongy composites promoted wound healing, as determined by in vivo tests, wound contraction ratio, average healing time, and histological examination. These results indicate that the spongy composites can serve as effective antibacterial wound dressings.

Evaluation of symptoms and risks in stable chronic obstructive pulmonary disease patients with radiographic bronchiectasis.

OBJECTIVE: To investigate the presence of previously undiagnosed radiographic bronchiectasis in stable chronic obstructive pulmonary disease (COPD) patients using high resolution computed tomography (HRCT) and to evaluate the effect of radiographic bronchiectasis on the symptoms and risks in stable COPD patients. METHODS: From May 2012 to April 2014, there were 347 patients enrolled in COPD database. Data describing the general conditions, the frequency of acute exacerbations the year before, COPD assessment test, modified medical research council (mMRC) score, spirometric classification, and HRCT were collected. COPD patients were classified into two groups: COPD with bronchiectasis and COPD without bronchiectasis. The clinical characteristics of both groups were compared. RESULTS: Bronchiectasis was presented in 18.4% (n = 64). The proportion of smokers, smoking index, and forced expiratory volume in 1 second predicted value were 62.5%, 27.3 ± 13.2, 48.2 ± 26.4, respectively, in the bronchiectasis group, which were lower than those of the group without bronchiectasis (82.0%, 32.6 ± 17.6, and 57.9 ± 18.8) (P < 0.05). Complications, COPD assessment test (CAT) and the rate of CAT ≥ 10 in the bronchiectasis group were 2.8 ± 1.7,13.6 ± 7.4 and 26.6%, respectively, which were higher than those of the group without bronchiectasis (2.3 ± 1.5,11.3 ± 6.0, and 11.7%) (P < 0.05). The proportion of type D (high-risk more-symptoms) in the bronchiectasis group was 50.0%; it was significantly higher than that of 35.7% in the group without bronchiectasis (P < 0.05). CONCLUSIONS: COPD with bronchiectasis is associated with more complications, symptoms, and risks. More attention should be paid to the treatment of COPD with bronchiectasis to reduce the frequency of exacerbation and improve the health status.