Icariin promotes the proliferation and osteogenic differentiation of bone-derived mesenchymal stem cells in patients with osteoporosis and T2DM by upregulating GLI-1.

BACKGROUND: The function of mesenchymal stem cells (MSCs) from patients with osteoporosis (OP) is impaired and worsens in patients with type 2 diabetes mellitus (T2DM). Icariin (ICA) is the major active flavonoid glucoside isolated from traditional Chinese herbal Epimedium pubescens, and confirmed able to improve bone mass of OP patients. OBJECTIVE: To investigate the effect of ICA on the proliferation and osteogenic differentiation of bone-derived MSCs (BMSCs) from patients with OP and T2DM and uncover the potential mechanism. METHODS: BMSCs were treated with ICA, and proliferation and osteogenic potency were evaluated using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and detection of osteogenic markers (ALP, RUNX2, SPP1, COL1A1, and mineralized nodules) was performed. RNA sequencing and bioinformatic analysis were performed to identify differentially expressed genes (DEGs) after ICA treatment and screen proliferation- and osteogenic differentiation-related processes. Gene gain and loss were performed to confirm the role of the key candidate gene. RESULTS: ICA significantly promoted the proliferation and osteogenic differentiation of BMSCs. A total of 173 DEGs were identified after ICA treatment. Six DEGs (GLI-1, IGF2, BMP6, WNT5A, PTHLH, and MAPK14) enriched in both proliferation- and osteogenic differentiation-related processes were screened; GLI-1 had the highest validated |log2FC| value. Overexpression of GLI-1 enhanced the proliferation and osteogenic differentiation of BMSCs, and knockdown of GLI-1 weakened the positive effect of ICA on BMSCs. CONCLUSION: ICA promoted the proliferation and osteogenic differentiation of impaired BMSCs by upregulating GLI-1.

New-Onset Arthritis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its symptoms, but there are also many adverse events. Joint diseases caused by COVID-19 vaccine have been reported in many studies. Some are well-controlled arthritis patients who developed arthritis after COVID-19 vaccination, while others are new-onset joint pain and swelling problems after COVID-19 vaccination. The purpose of this systematic review is to examine the literature reports in existing databases and analyze the incidence of new-onset arthritis after COVID-19 vaccination. We included 31 eligible articles and described 45 patients, ranging in age from 17 to over 90, with more females than males. The majority (84.4%) of patients received the adenovirus vector vaccine (ChAdOx1) and the mRNA-based vaccine (BNT126b2 and mRNA-1273). Most (64.4%) patients developed joint-related symptoms after the first dose of vaccine, and 66.7% developed symptoms within the first week of vaccination. The joint symptoms involved were mainly joint swelling, joint pain, limited range of motion, and so on. A total of 71.1% of the patients involved multiple joints, both large and small; 28.9% of patients involved only a single joint. Some (33.3%) patients were confirmed by imaging, and the most common diagnoses were bursitis and synovitis. Two nonspecific inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were monitored in almost all cases, and all patients showed varying degrees of increase in these two markers. Most of the patients received the treatment of glucocorticoid drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical symptoms markedly improved in most patients, with 26.7% making a full recovery and no relapse after a few months of follow-up. To determine whether there is a causal relationship between COVID-19 vaccination and the triggering of arthritis, large-scale and well-controlled research studies are needed in the future to verify this relationship and to further study its pathogenesis in detail. Clinicians should raise awareness of this complication with a view to early diagnosis and appropriate treatment.

A gene expression profile for the lower osteogenic potent of bone-derived MSCs from osteoporosis with T2DM and the potential mechanism.

BACKGROUND: Osteoporosis (OP) patients complicated with type II diabetes mellitus (T2DM) has a higher fracture risk than the non-diabetic patients, and mesenchymal stem cells (MSCs) from T2DM patients also show a weaker osteogenic potent. The present study aimed to provide a gene expression profile in MSCs from diabetic OP and investigated the potential mechanism. METHODS: The bone-derived MSC (BMSC) was isolated from OP patients complicated with or without T2DM (CON-BMSC, T2DM-BMSC). Osteogenic differentiation was evaluated by qPCR analysis of the expression levels of osteogenic markers, ALP activity and mineralization level. The differentially expressed genes (DEGs) in T2DM-BMSC was identified by RNA-sequence, and the biological roles of DEGs was annotated by bioinformatics analyses. The role of silencing the transcription factor (TF), Forkhead box Q1 (FOXQ1), on the osteogenic differentiation of BMSC was also investigated. RESULTS: T2DM-BMSC showed a significantly reduced osteogenic potent compare to the CON-BMSC. A total of 448 DEGs was screened in T2DM-BMSC, and bioinformatics analyses showed that many TFs and the target genes were enriched in various OP- and diabetes-related biological processes and pathways. FOXQ1 had the highest verified fold change (abs) among the top 8 TFs, and silence of FOXQ1 inhibited the osteogenic differentiation of CON-BMSC. CONCLUSIONS: Our study provided a comprehensive gene expression profile of BMSC in diabetic OP, and found that downregulated FOXQ1 was responsible for the reduced osteogenic potent of T2DM-BSMC. This is of great importance for the special mechanism researches and the treatment of diabetic OP.

Intramedullary Nail Fixation by Suprapatellar and Infrapatellar Approaches for Treatment of Distal Tibial Fractures.

OBJECTIVE: To compare the functional and alignment outcomes of intramedullary nail fixation using suprapatellar and infrapatellar approaches in treating distal tibial fractures. METHODS: In this retrospective study, 132 patients with distal tibial fractures (87 men, 45 women) ranging in age from 20 to 66 years were treated with intramedullary nails using the suprapatellar (69 patients) or infrapatellar (63 patients) approach. The radiographic alignment outcomes and ankle function were compared between the two groups. Multivariate logistic regression analyses were performed to determine which variety influenced ankle functional scores and whether the suprapatellar approach intervention demonstrated a protective effect. RESULTS: The mean follow-up time was 14.22 ± 2.31 months. The mean sagittal section angle of the fracture in the suprapatellar and infrapatellar approach groups was 3.20° ± 1.20° and 5.31° ± 1.23°, respectively (P < 0.001). The mean coronal section angle was 3.51° ± 0.89° and 5.42° ± 1.05°, respectively (P < 0.001). Three patients (4.3%) in the suprapatellar approach group and 15 patients (23.8%) in the infrapatellar approach group had poor fracture reduction (P < 0.001). The mean hind foot functional score and ankle pain score were 95.91 ± 4.70 and 35.91 ± 4.70 points, respectively, in the suprapatellar approach group and 85.20 ± 5.61 and 25.20 ± 5.61 points, respectively, in the infrapatellar approach group (P < 0.001 for both). In the comparison of ankle function, the multivariate logistic regression analyses demonstrated that the odds ratio in the suprapatellar approach group was about 7 times that in the infrapatellar approach group (odds ratio, 7.574; 95% confidence interval, 2.148-28.740; P = 0.002). Of the variants measured, the statistically significant risk factors for poor ankle function were AO type A3 (P = 0.016) and diabetes mellitus (P = 0.006). Sex and the operation interval were not statistically significant risk factors for poor ankle function. CONCLUSION: Intramedullary nailing using the suprapatellar approach facilitates simple fracture reduction, excellent postoperative fracture alignment, and few complications, giving it obvious advantages over the conventional infrapatellar approach. Additionally, the suprapatellar approach is a prognostic factor associated with postoperative ankle joint function.

In vitro anti-synovial sarcoma effect of diallyl trisulfide and mRNA profiling.

OBJECTIVE: Synovial sarcoma (SS) is a malignant soft tissue sarcoma and its natural history is a long, indolent clinical course followed by high rate of local recurrence and distant metastasis. Current therapies are still limited in increasing satisfactory of 5-year survival, especially for patients with recurrence and metastasis. Accordingly, finding new therapeutic drug for SS treatment is clinically urgent need. Diallyl trisulfide (DATS), a bioactive compound derived from garlic, is reported as a promising anti-cancer agent for various carcinomas. However, its effect on anti-SS remains unknown. This study investigated the anti-SS effect of DATS in human synovial sarcoma SW982 cells. METHODS: CCK-8 assay were used to examine the cell viability. High-content Imaging System was used to examine the apoptosis, intracellular ROS and autophagy. Flow cytometry was used to detect cell cycle. qPCR and Western blot were used to examine the expression of related mRNA and protein. High-throughput RNA-sequencing and bio-information analysis were used to investigate the mRNA profiling. RESULTS: The results showed a suppressive effect of DATS on tumor biology of SW982 cells including inducing apoptosis, triggering G2/M cell cycle arrest, elevating intracellular ROS and damaging mitochondria. Further high-throughput RNA-sequencing analysis clarified a comprehensive molecular portrait for DATS-induced transcriptional regulation. Besides, protein-protein interaction (PPI) analysis demonstrated that a network consisted of FOXM1, CCNA2, CCNB1, MYBL2, PLK1 and CDK1 might be response for DATS-induced G2/M cell cycle arrest and increased intracellular ROS. Notably, protein feature analysis revealed structure enrichment in microtubule network like kinesin motors domain, and tubulin domain. Molecular function analysis suggested that DATS-induced dysfunction of microtubule network might be the major cause for its effect on cell cycle arrest and successive apoptosis. Furthermore, 28 hub genes (including KIF2C, PLK1, CDK1, BIRC5, CCNB2, CENPF, TPX2, TOP2A and so on) were determined. Finally, pathway analysis showed that DATS-induced differentially expressed genes were mainly involved in cell cycle. CONCLUSION: Collectively, our findings for the first time provided the DATS-induced cellular response and transcriptional profiling of SW982 cells, which proposes that suppression of DATS on SS is multi-targeted and represent a therapeutic evidence for SS.

Cornuside I promoted osteogenic differentiation of bone mesenchymal stem cells through PI3K/Akt signaling pathway.

BACKGROUND: Osteoporosis is a common disease closely associated with aging. In this study, we aimed to investigate the role of Cornuside I in promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the potential mechanism. METHODS: BMSCs were isolated and treated with different concentrations of Cornuside I (0, 10, 30, 60 µM). Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. RNA sequencing was performed on the isolated BMSCs with control and Cornuside I treatment. Differentially expressed genes were obtained by the R software. Alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR and western blot were used to detect the expression of osteoblast markers. RESULTS: Cornuside I treatment significantly improved BMSC proliferation. The optimal dose of Cornuside I was 30 µM (P < 0.05). Cornuside I dose dependently increased the ALP activity and calcium deposition than control group (P < 0.05). A total of 704 differentially expressed genes were identified between Cornuside I and normal BMSCs. Cornuside I significantly increased the PI3K and Akt expression. Moreover, the promotion effects of Cornuside I on osteogenic differentiation of BMSCs were partially blocked by PI3K/Akt inhibitor, LY294002. CONCLUSION: Cornuside I plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of PI3K/Akt signaling pathway.

Minimally invasive (sinus tarsi) approach for calcaneal fractures.

BACKGROUND: According to the anatomic characteristics of the calcaneus and the sinus tarsi approach, we designed a combined plate. The goal of this study was to retrospectively assess the functional outcomes and complications of treatment with our self-designed plate. METHODS: From March 2014 to October 2015, 18 patients with closed calcaneal fractures (14 Sanders type II and 4 type III) were treated with our combined locking plate through a minimally invasive sinus tarsi approach. All patients underwent both clinical and radiological evaluations. RESULTS: The follow-up duration for all patients ranged from 6 to 13.5 months. The radiographs demonstrated significant corrections of the calcaneal width, length, height, Böhler angle, and Gissane angle from preoperatively to 3 months postoperatively and the last follow-up. However, there were no significant differences in the variables between 3 months postoperatively and the last follow-up. The mean Maryland foot score was 88.1 ± 8.8, in which excellent outcomes were achieved in 11 patients, good in 4, and fair in 3 (excellent and good rate, 83.3% (15 of 18)). No statistical significances in the mean Maryland foot score (88.1 ± 8.8 vs 87.8 ± 10.1, p = 0.9), and the excellent and good rate (85.7 vs 75.0%, p = 1.0) was found between type II and type III fractures. No complications were observed in all fractured feet. CONCLUSION: Treatment with our self-designed combined plate through a sinus tarsi approach may be safe and effective for type II and type III calcaneal fractures.

Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China.

INTRODUCTION: The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7). METHODS AND ANALYSIS: 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12-15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed. ETHICS AND DISSEMINATION: Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance. TRIAL REGISTRATION NUMBER: NCT02736240.

[Investigation on distribution of Yersinia enterocolitica in Henan province between 2005 and 2011].

OBJECTIVE: To investigate the distribution of Yersinia enterocolitica in Henan province from 2005 to 2011. METHODS: A total of 6700 samples of stool specimen were collected from diarrhea patients and different domestic animals between 2005 and 2011 from Zhengzhou, Suixian and Dengfeng, as well as flies and the daub specimens of raw and cooked meat products. The bacteria were isolated by cold enrichment method, analyzed by the systematic biochemistry to determine the serotypes and bio-types, and tested the virulence genes by PCR method. RESULTS: A total of 216 strains of Yersinia enterocolitica were isolated from 11 kinds of animal hosts and foods, while 29.63% (64/216) of them were from swine. The dominant epidemic serotypes of the Yersinia enterocolitica were O: 5 and O: 8, accounted for 23.2% (50/216) and 20.4% (44/216), respectively; type 1A was the dominant bio-type, accounted for 84.7% (183/216). The dominant serotype and bio-type differed a lot among various hosts.16 pathogenic strains were isolated from swine, followed by diarrhea patients (6 strains) and dogs (6 strains). CONCLUSION: The distribution of the host of Yersinia enterocolitica was widespread, while swine was the dominant animal host.

[Clinical trial on the prevention of diarrhea by oral BIFICO for infants aged 1-6 years].

OBJECTIVE: To investigate the prevention of diarrhea by oral BIFICO for infants aged 1-6 years. METHODS: 490 cases of infants were randomly divided after age stratification: the experimental group (n = 247) and the control group (n = 243). Based on principles of randomized double-blind and placebo-controlled, the infants were given BIFICO (dedicated clinical research)therapy for 4 consecutive days, then observed for 21 days. 25 days composed a cycle. They were observed total 5 cycles. During the study period, principles for "the diarrhoea patients must be detected", follow-up visited the participant infants and conducted etiology detection by way of sampling for diarrhea infants. Evaluate the prevention efficacy of diarrhea by oral BIFICO for infants aged 1-6 years. RESULTS: A total of 480 completed all study. 120 and 95 infants in the control group and experimental group were detected with diarrhea. The incidence of diarrhea was 50.85% and 38.93% in these two guoup, respectively. The difference has statistical significance (chi2 = 4.175, P = 0.041). In the third observation period, the infants in the control group had a higer incidence of diarrhea compared with which in the experimental group (chi2 = 4.415, P = 0.036). 14 strains of rotavirus, 3 strains of norovirus, 3 strains of sappovirus, 2 strains of adenovirus, 5 strains of salmonella and 4 strains of Shigella were check out in 128 samples. CONCLUSION: Oral BIFICO can paly certain preventive role on diarrhea, and decrease the incidence of diarrhea in infants aged 1-6 years.

Comparison of the pathologic and pathogenic features in six different regions of postmortem brains of three patients with fatal familial insomnia.

Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by rapidly progressive insomnia, prominent autonomic alterations and behavioral disturbance. The D178N mutation of the prion protein gene (PRNP) on chromosome 20 in conjunction with methionine at codon 129 is a molecular feature. Although the neuropathological characteristics of FFI are well documented, the neuropathologic and pathogenic features of FFI patients remain poorly understood. Six brain regions of postmortem brains from 3 FFI patients were examined using immunohistochemistry, western blot analyses and quantitative real-time PCR. In all 3 brain specimens, reactive astrogliosis was found to be more severe in the thalamus than in the cortex regions. Western blot analyses showed that all three brains expressed PrP, but only 2 were associated with significantly weak proteinase K (PK) resistance. However, the conformational stabilities of PrPSc in the 3 FFI brains were significantly weaker than those presented in a G114V genetic Creutzfeldt-Jakob disease (gCJD) case. Immunohistochemistry and western blot analyses showed comparable amounts of neuron-specific enolase (NSE)-positive stained cells and NSE protein among the different regions in the three brains. In addition, the transcriptional levels of glial fibrillary acidic protein (GFAP) and NSE-specific mRNAs were coincident with the expression of these proteins. In conclusion, in the present study, we described the detailed regional neuropathology of FFI cases.

[Analysis of etiological surveillance results of Shigella spp between 2009 and 2010 in Henan province].

OBJECTIVE: To explore the etiologic characteristics of bacillary dysentery found in Henan province, between year 2009 and 2010. METHODS: In order to explore the distribution of bacterial types, drug susceptibility and the virulence gene carrier situation, 482 strains of Shigella isolated in Henan province between 2009 and 2010 were pathogen-detected and analyzed by serotype screening, anti microbial sensitivity test and PCR methods. RESULTS: The 482 isolated strains were confirmed to be Shigella by both morphological and biochemical tests. The Shigella strains were divided into 13 serotypes in 2 groups, namely Shigella flexneri (B group) accounting for 72.0% (347/482) and Shigella sonnei (D group), accounting for 28.0% (135/482). The detection rate of Serotype F2a, as the dominant type of Shigella flexneri, decreased from 43.4% (106/245) in 2009 to 33.8% (80/237) in 2010; while the detection rate of Shigella sonnei increased from 13.1% (32/245) to 43.5% (103/237) in the same period. The results of microbial sensitivity tests carried out in year 2009 and 2010, both showed that over 98% of the 185 studied strains were resistant to ampicillin (AMP), trimethoprim-pyrimidine (TMP), tetracycline (TE), streptomycin (S) and nalidixic acid (NA).182 strains were recruited in the virulence factors detection, 67.6% (123/182) of which carried Shigella Enterotoxin 1B (set1B), Shigella Enterotoxin 2 (set2), invasive plasmid antigen H (ipaH) or invasion-related virulence factors (ial) and 24.2% (44/182) of which carried 3 virulence factors mentioned above. CONCLUSION: The prevalent serotypes of Shigella in Henan province have changed in recent years. The isolated strains showed high resistance to common antibacterial drugs and generally carried virulence factors.

Clinical, histopathological and genetic studies in a family with fatal familial insomnia.

We compared clinical data from two related Chinese patients with fatal familial insomnia (FFI) and collected information about their pedigree. The clinical features in the two cases were similar and included initial progressive insomnia and sympathetic activation, which persisted throughout the clinical course. A total of 135 members of this family, across seven generations, were retrospectively investigated. Eleven family members, including the two FFI cases, were found to have died with similar neurological problems. Analysis of PRNP in 32 family members revealed eleven carrying the D178N allele, including the two FFI patients. Spongiform degeneration in brains was not found, but gliosis was obvious in the thalamus of the two cases at postmortem. Proteinase K-resistant prion protein (PrP) was not found in proband's brain by immunohistochemistry, but observed in some areas of brain for both cases by PrP-specific Western blot. Investigation of the pedigree has led to the identification of an additional 9 family members who had similar clinical symptoms and 9 currently healthy individuals with the D178N mutation.

[Analysis on clinical and epidemiological characteristics of severe cases infected by EV71].

OBJECTIVE: To explore the clinical and epidemiological characteristics of serious cases of hand-foot-and-mouth disease (HFMD) infected by EV71, in order to provide scientific evidence for prevention and control of HFMD. METHODS: Information was collected by questionaires through consulting medical cases. Data was input by Epidata, and analysed by software SAS 9.13. RESULT: 201 severe cases were investigated. 84.65% of the cases were below 3 years old. The youngest one was 5 months and the oldest one was 8 years old. The ratio for male and female was 2.2: 1.85. 08% of the cases were distributed sporadically. 51.74% of them lived in rural, 29.36% of them lived in urban and 19.9% of them lived at the fringe area of rural and urban. 81.59% of the cases became serious between 1 and 4 days after infected. 100% cases had fever and 99.95% of them had a rash. 96.52% of them had nerve system symptoms. The main complications were virulent spinal encephalitis, pneumonia and breathing exhaustion. 98.01% of the patients were recovered or cured. CONCLUSION: The cases aged below 3 years old are high risk persons. Rural area and the fringe area of rural and urban are the key area for disease control. 1-4 days after onset is the key period to prevent complications.

Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: The current influenza pandemic calls for a safe and effective vaccine. We assessed the safety and immunogenicity of eight formulations of 2009 pandemic influenza A H1N1 vaccine produced by ten Chinese manufacturers. METHODS: In this multicentre, double-blind, randomised trial, 12 691 people aged 3 years or older were recruited in ten centres in China. In each centre, participants were stratified by age and randomly assigned by a random number table to receive one of several vaccine formulations or placebo. The study assessed eight formulations: split-virion formulation containing 7.5 microg, 15 microg, or 30 microg haemagglutinin per dose, with or without aluminium hydroxide adjuvant, and whole-virion formulation containing 5 microg or 10 microg haemagglutinin per dose, with adjuvant. All formulations were produced from the reassortant strain X-179A (A/California/07/2009-A/PR/8/34). We analysed the safety (adverse events), immunogenicity (geometric mean titre [GMT] of haemagglutination inhibition antibody), and seroprotection (GMT >or=1:40) of the formulations. Analysis was by per protocol. Two sites registered their trial with ClinicalTrials.gov, numbers NCT00956111 and NCT00975572. The other eight studies were registered with the State Food and Drug Administration of China. FINDINGS: 12 691 participants received the first dose on day 0, and 12 348 participants received the second dose on day 21. The seroprotection rate 21 days after the first dose of vaccine ranged from 69.5% (95% CI 65.9-72.8) for the 7.5 microg adjuvant split-virion formulation to 92.8% (91.9-93.6) for the 30 microg non-adjuvant split-virion formulation. The seroprotection rate was 86.5% (796 of 920; 84.1-88.7) in recipients of one dose of the 7.5 microg non-adjuvant split-virion vaccine compared with 9.8% (140 of 1432; 8.3-11.4) in recipients of placebo (p<0.0001). One dose of the 7.5 microg non-adjuvant split-virion vaccine induced seroprotection in 178 of 232 children (aged 3 years to <12 years; 76.7%, 70.7-82.0), 211 of 218 adolescents (12 years to <18 years; 96.8%, 93.5-98.7), 289 of 323 adults (18-60 years; 89.5%, 85.6-92.6), and 118 of 147 adults older than 60 years (80.3%, 72.9-86.4), meeting the European Union's licensure criteria for seroprotection in all age-groups. In children, a second dose of the 7.5 microg formulation increased the seroprotection rate to 97.7% (215 of 220, 94.8-99.3). Adverse reactions were mostly mild or moderate, and self-limited. Severe adverse effects occurred in 69 (0.6%, 0.5-0.8) recipients of vaccine compared with one recipient (0.1%, 0-0.2) of placebo. The most common severe adverse reaction was fever, which occurred in 25 (0.22%; 0.14-0.33) recipients of vaccine after the first dose and four (0.04%; 0.01-0.09) recipients of vaccine after the second dose compared with no recipients of placebo after either dose. INTERPRETATION: One dose of non-adjuvant split-virion vaccine containing 7.5 microg haemagglutinin could be promoted as the formulation of choice against 2009 pandemic influenza A H1N1 for people aged 12 years or older. In children (aged <12 years), two 7.5 mug doses might be needed. FUNDING: Sinovac Biotech, Hualan Biological Bacterin, China National Biotec Group, Beijing Tiantan Biological Products, Changchun Institute of Biological Products, Changchun Changsheng Life Sciences, Jiangsu Yanshen Biological Technology Stock, Zhejiang Tianyuan Bio-Pharmaceutical, Lanzhou Institute of Biological Products, Shanghai Institute of Biological Products, and Dalian Aleph Biomedical.

Characterization of Salmonella enterica serotype typhimurium from outpatients of 28 hospitals in Henan province in 2006.

OBJECTIVE: To characterize the diarrheal patients with Salmonella typhimurium (S. typhimurium) infections and to set up the first baseline for S. typhimurium pulsed-field gel electrophoresis (PFGE) patterns in Henan province, thus laying a foundation for comprehensive surveillance of Salmonella in human as well as foods. METHODS: S. typhimurium isolates recovered from outpatients with diarrhea in Henan province from May to October of 2006 were characterized. Antimicrobial susceptibility tests of 8 antimicrobial agents and PFGE were carried out to analyze the S. typhimurium isolates. RESULTS: Twenty-four (0.9%) S. typhimurium isolates were identified from 2661 stool specimens of diarrheal cases. Eighty-eight percent of isolates showed resistance to at least one antimicrobial agent. The resistance to chloramphenicol (79%) was most common. Fifty-eight percent of isolates were resistant to ciprofloxacin. All the 14 ciprofloxacin-resistant isolates were resistant to more than five antimicrobial agents. Thirty-three percent of S. typhimurium isolates were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (R-type ACSSuT). Eight antimicrobia-resistant phenotypes were found among the 24 isolates in 16 PFGE patterns. CONCLUSION: The rate of multidrug-resistant S. typhimurium is relatively high in S. typhimurium PFGE patterns of Henan province. Multidrug-resistant S. typhimurium should be considered a public health threat.

[Studies on heredity rule of the first genealogy regarding fatal familial insomnia in Henan province].

OBJECTIVE: To investigate the epidemiological, genealogic characteristic, familial history of the families with fatal familial insomnia, its clinical and pathological features as well as the heredity rule of related genes. METHODS: 135 familial members of 7 eras were studied. Vein blood samples from patients as well as from some familial members were collected. PRNP gene was studied with PCR, its serial was determined and then authenticated with Nsp I . Brain tissue was obtained for neuropathological test and PrP(Sc) test with Western blot method. RESULTS: Clinical symptoms of the 2 diagnosed cases were typical. 11 familial members died of similar neural disease. 32 samples of their familial members, codon at D178N of PRNP of 11 members was mutated, with mutation rate as 34.38% while D129N showed as methionine. Brain tissue of both probands denaturalized into spongiform and the nerve fiber was absent but PrP(Sc) protein was identified. CONCLUSION: Genealogy was described in the family with fatal familial insomnia since the patients had typical clinical symptoms and pathological characteristics. It seemed necessary to confirm cases of fatal familial insomnia and their genealogy with epidemiological data and to investigate its gene characteristics as well as with neuropathological and Western blot tests.

[Analysis for clinical and genetic characteristics of a sporadic FFI case].

OBJECTIVE: To report and study a case of sporadic family fatal insomnia (SFFI) on its. METHODS: Investigate clinical characteristics and family disease history of a suspect FFI patient. His clinical characteristic was analyzed, he and his 14 family members genomic DNA was extracted by standard techniques from their and blood detected with polymerase chain reaction (PCR) method and DNA sequencing to find out his prion protein (PrP) gene mutation. The patient's CSF was detected with Western-Blot method for 14-3-3 brain protein. RESULTS: The patient was diagnosed as an sporadic FFI by his developed sleep disturbance and changes in sleep-awake rhythm, motor abnormalities, mental disorder, dementia, autonomic dysfunction; his family history; his 14-3-3 brain protein-positive (CSF) and analysis results of his PrP gene (codon point mutation D178N and methionine homozygosity at position 129M/M). Suggesting that in the future to identify CJD and FFI patients, screening should focus on clinical symptoms and laboratory results. The PrP gene of 14 family members did not appear Mutation, and there is no person suffering from the same disease. CONCLUSIONS: The case was diagnosed as a sporadic familial fatal insomnia. Analysis of suspicious patients' genomic DNA for PrP gene mutation might be very important for FFI diagnosis because there exist many difficulties in clinical laboratory evaluation. This patient might be the first SFFI patient reported in China and the case finding might have momentousness in clinical and basical study.