Dynamic change of clinical characteristics in a cured patient with influenza A （H7N9） virus infection

To the editor：During the spring of 2013,a novel avian-origin influenza A （H7N9） virus emerged and spread among humans in China.1 In this report,we described the dynamic change of clinical characteristics in a case of H7N9 virus infection,who got cured without treatment with invasive mechanical ventilation.     

Radiological features of lung changes caused by avian influenza subtype A H5N1 virus: report of two severe adult cases with regular follow-up

Several subtypes of avian influenza A have been shown to cross the species barrier and infect humans, leadingto human cases of avian influenza） Till June 2, 2009, globally there were 433 confirmed human cases of avian influenza caused by H5N1 virus, with a death rate of 60.5%.3 This is far higher than the reported 11% death rate of severe acute respiratory syndrome （SARS）.4 The epidemiologic features of human case of influenza A subtype H5N1 virus infection consist of high incidence rate in cold weather, high susceptibility in population of younger age associated with rapid onset of the disease and devastating illness in humans.12＇5＇6 H5N1 virus is mostly transmitted to humans directly through contact with infected birds or their secretions and the patients present with an influenza type illness with fever, cough, sore throat, malaise, and gastrointestinal symptoms; which can result in a rapidly progressive primary viral pneumonia and respiratory failure.2 Patients above the age of 5 years are likely to have an adverse course of disease.5     

Bedside chest radiography of novel influenza A （H7N9） virus infections and follow-up findings after short-time treatment

Background Influenza A （H7Ng） virus infections were first observed in China in March 2013.This type virus can cause severe illness and deaths,the situation raises many urgent questions and global public health concerns.Our purpose was to investigate bedside chest radiography findings for patients with novel influenza A （H7Ng） virus infections and the followup appearances after short-time treatment.Methods Eight hospitalized patients infected with the novel influenza A （H7Ng） virus were included in our study.All of the patients underwent bedside chest radiography after admission,and all had follow-up bedside chest radiography during their first ten days,using AXIOM Aristos MX and/or AMX-Ⅳ portable X-ray units.The exposure dose was generally 90 kV and 5 mAs,and was slightly adjusted according to the weight of the patients.The initial radiography data were evaluated for radiological patterns （ground glass opacity,consolidation,and reticulation）,distribution type （focal,multifocal,and diffuse）,lung zones involved,and appearance at follow-up while the patients underwent therapy.Results All patients presented with bilateral multiple lung involvement.Two patients had bilateral diffuse lesions,three patients had unilateral diffuse lesions of the right lobe with multifocal lesions of the left lobe,and the remaining three had bilateral multifocal lung lesions.The lesions were present throughout bilateral lung zones in three patients,the whole right lung zone in three patients with additional involvement in the left middle and/or lower lung zone（s）,both lower and middle lung zones in one patient,and the right middle and lower in combination with the left lower lung zones in one patient.The most common abnormal radiographic patterns were ground glass opacity （8/8）,and consolidation （8/8）.In three cases examined by CT we also found the pattern of reticulation in combination with CT images.Four patients had bilateral and four had unilateral pleural effusion.After a short period of treatment the pneumonia in one patient had significantly improved and three cases demonstrated disease progression.In four cases the severity of the pneumonia fluctuated.Conclusions In patients with influenza A （H7N9） virus infection,the distribution of the lung lesions are extensive,and the disease usually involves both lung zones.The most common imaging findings are a mixture of ground glass opacity and consolidation.Pleural effusion is common.Most cases have a poor short-time treatment response,and seem to have either rapid progressive radiographic deterioration or fluctuating radiographic changes.Chest radiography is helpful for evaluating patients with severe clinical symptoms and for follow-up evaluation.     

Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A（H1N1） virus

Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A（H1N1）pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A（H1N1）pdm09 and seasonal influenza A virus （FLU A） was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR （rRT-PCR） assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A（H1N1）pdm09 was observed.The percentage of positive cases for A（H1N1）pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September （2.2％） and October （3.3％）,revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 （1.8％） were HRV-positive,which was significantly lower than that reported previously in Beijing （15.4％ to 19.2％） （P ＜0.01）.Overall,6 samples were positive for both A（H1N1）pdm09 and HRV,which represented a positive relative frequency of 1.60％ and 2.08％ HRV,considering the A（H1N1）pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 （95％ CI 0.32; 2.44,P=0.80）.Conclusions HRVs and A （H1N1）pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A（H1N1）pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A（H1N1）pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.     

Potential infections of H5N1 and H9N2 avian influenza do exist in Guangdong populations of China

Background Southeast China is one of the sites of influenza origin. During 2003-2004, nine avian influenza outbreaks took place in Guangdong Province. But no human case was reported. To examine the status of potential human infection by human influenza （H1N1, H3N2） and avian influenza （H5N1, H7N7, H9N2） in the avian influenza epidemic area of Guangdong Province, China, we conducted a seroepidemiologic survey in the people of this area from April to June of 2004.
Methods Three out of 9 H5N1 avian influenza affected poultry areas in Guangdong were randomly selected, and the population living within 3 kilometers of the affected poultries were chosen as the survey subjects. One thousand two hundred and fourteen people were selected from 3 villages at random. Human and avian influenza antibody titers were determined by hemagglutination-inhibition （HI） test and microneutralization test （MNT）.
Results The positive rate of antibody to H5N1 was 3.03% in the occupational exposure group and 2.34% in general citizens group; that of H9N2 was 9.52% in the occupational exposure group and 3.76% in the general citizens group. Moreover one case in the occupational exposure group was positive for H7N7. One year later, all previously positive cases had become negative except for one H5N1-positive case.
Conclusion The observations imply that H5N1 and H9N2 avian influenza silent infections exist in Guangdong populations.     

Predicted epitopes of H5N1 bird flu virus by bioinformatics method: a clue for further vaccine development

To the Editor： Bird flu or avian flu, caused by H5N1 virus, is a new emerging infectious disease. It is noted that this H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in many countries. The continued westward dissemination of H5N1 influenza A viruses in avian populations and the nearly 50% mortality of humans infected with H5N1 are a source of great international concern.1 Providing sufficient antiviral drugs and development and approval of new vaccines are the keys for control of the possible emerging pandemic of this atypical influenza.1＇2 Based on the advance in bioinformatics, the immunomics becomes a new alternative in vaccine development.3 Advanced technologies for vaccine development, such as genome sequence analysis, microarray, proteomics approach, high-throughput cloning, bioinformatics database tools and computational vaccinology can be applied for vaccine development of several diseases including new emerging diseases.     

High-level expression, purification and characterization of codon-optimized recombinant hemagglutinin 5 proteins in mammalian cells

Background Numerous Asian cases of avian influenza virus infection, especially the highly pathogenic strain H5N1, in humans have raised the concern that another influenza pandemic is close. However, there are no effective therapeutic drugs or preventative vaccines available. Hemagglutinin is the membrane glycoprotein of avian influenza virus responsible for receptor binding to human cells and the main immunogenic protein that elicits a strong immune response. Although this protein is of great importance to the study of pathogenesis and vaccine development, its expression and purification are difficult due to high levels of glycosylation. Methods In this study, we expressed codon-optimized, full-length hemagglutinin 5 （H5） protein fused with a human IgG Fc tag （H5-Fc） in HEK293 cells. To enhance secretion of this protein, we also deleted the transmembrane domain and the intracellular domain of the H5 protein （H5ATM-Fc）. Purified proteins were obtained using a protein A column. Results ELISA revealed that the yield of soluble H5ATM-Fc protein in the supernatant was about 20 mg/L. Western blotting and fluorescence activated cell sorter （FACS） indicated that the purified H5 protein was correctly folded and biologically active. Conclusion Purification of H5 proteins from mammalian cells could be used for large-scale production of recombinant H5 protein for basic scientific research or the development of vaccines.     

Generation and characterization of a cold-adapted attenuated live H3N2 subtype influenza virus vaccine candidate

Background H3N2 subtype influenza A viruses have been identified in humans worldwide, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. The aim of this study was to establish a system for rescuing of a cold-adapted high-yielding H3N2 subtype human influenza virus by reverse genetics, Methods In order to generate better and safer vaccine candidate viruses, a cold-adapted high yielding reassortant H3N2 influenza A virus was genetically constructed by reverse genetics and was designated as rgAA-H3N2. The rgAA-H3N2 virus contained HA and NA genes from an epidemic strain A/Wisconsin/67/2005 （H3N2） in a background of internal genes derived from the master donor viruses （MDV）, cold-adapted （ca）, temperature sensitive （ts）, live attenuated influenza virus strain A/Ann Arbor/6/60 （MDV-A）. Results In this presentation, the virus HA titer of rgAA-H3N2 in the allantoic fluid from infected embryonated eggs was as high as 1：1024. A fluorescent focus assay （FFU） was performed 24-36 hours post-infection using a specific antibody and bright staining was used for determining the virus titer. The allantoic fluid containing the recovered influenza virus was analyzed in a hemagglutination inhibition （HI） test and the specific inhibition was found. Conclusion The results mentioned above demonstrated that cold-adapted, attenuated reassortant H3N2 subtype influenza A virus was successfully generated, which laid a good foundation for the further related research.     

Critical influenza (H1N1) pneumonia: imaging manifestations and histopathological findings

Background  The global outbreak of influenza A (H1N1) has led to the Ministry of Health of China listing it as one of the A-class infectious diseases. Pneumonia is the most serious complication of influenza A, commonly causing death. Populations are ordinarily susceptible to influenza A. This study aimed to investigate the imaging manifestation features of critical influenza A (H1N1) pneumonia and to improve its diagnostic techniques.

Methods  A total of seven death cases from critical influenza A (H1N1) pneumonia were retrospectively analyzed on their imaging manifestations and autopsy data. Pulmonary CT scanning was performed for five cases, with one receiving additional chest X-ray and chest CT scanning, and chest postero-anterior position X-ray examination was performed for other two. Autopsy was performed for five cases and postmortem examinations were performed for other two cases.

Results  The seven cases of influenza A showed critical manifestations in 4–7 days after symptoms onset, with two having basic diseases of diabetes and one being pregnant. Extensive blurry high-density shadows of bilateral lungs were found in three cases, which were most obvious in middle and inferior parts of lungs. Pulmonary CT scanning revealed bilateral flaky parenchymal shadows in peripheral, dorsal and fundus segments of the middle-inferior parts of lungs, with one case of complicated pneumothorax, atelectasis and pleural effusion and another case of thin-walled cavity and dilated bronchi shadows in the superior parts of lungs.

Conclusions  Diagnostic imaging is an important assessing tool for critical influenza A (H1N1) pneumonia. The imaging manifestations are characteristic instead of being specific. The definitive diagnosis can be made in combination with clinical examinations and laboratory tests.

     

Gene expression profiles of ERCC1, TYMS, RRM1, TUBB3 and EGFR in tumor tissue from non-small cell lung cancer patients

Background Personalized medicine becomes essential in lung cancer treatment, however lung-cancer-related gene expression profiles in Chinese patients remain unknown. In this study, the correlation of gene expression profiles and clinical characteristics in non-small-cell lung cancer （NSCLC） was investigated. Methods Seventy-six Chinese patients with NSCLC were enrolled in the study to investigate mRNA expression profiles of excision repair cross complement group 1 （ERCC1）, thymidylate synthetase （TYMS）, ribonucleotide reductase （RRM1）, class Ill 13-tubulin （TUBB3）, and epidermal growth factor receptor （EGFR） genes and their correlation with patient clinical characteristics. A novel liquidchip technology was used to detect mRNA expression levels in formalin fixed paraffin embedded tumor pathology samples. The relationships between gene expression and clinical characteristics were assessed using the Mann-Whitney test. Results ERCC1 mRNA levels were higher in tumors from patients with metastatic disease than patients with non- metastatic disease （P=-0.021）, and higher in adenocarcinomas than squamous cell carcinomas （P=0.006）. Increased TUBB3 mRNA expression levels were found in patients with performance status （PS） 1 in comparison with PS 0 （P=0.049）, with poorly differentiated tumors in comparison with tumors that were moderately and well differentiated （P 〈0.000 1）, and with advanced stage in comparison with early stage disease （P 〈0.000 1）. Conclusions ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poorly differentiated tumors and in advanced stage NSCLC, which indicates the poor prognosis.     

Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

In February 2005, Gefitinib （Iressa）, a small-molecular .epidermal growth factor receptor and tyrosine kinaseinhibitor, was approved in China as an anticancer agent for patients with advanced （local or metastatic） non-small cell lung cancer （NSCLC）, who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.1 However, these adverse events are generally mild in severity and reversible on cessation of the treatment. Therefore, gefitinib has been regarded as a relatively safe agent,     

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis： study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.     

Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.     

The role of central nervous system on hypoglycemia and the feasibility of the brain theory in traditional Chinese medicine on treatment of diabetes mellitus

The central nervous system （CNS） plays a key regulatory role in glucose homeostasis. In particular, the brain is important in initiating and coordinating protective counterregulatory responses when blood glucose levels fall. This may due to the metabolic dependency of the CNS on glucose, and protection of food supply to the brain. In healthy subjects, blood glucose is normally maintained within a relatively narrow range. Hypoglycemia in diabetic patients can increase the risk of complications, such as heart disease and diabetic peripheral neuropathy. The clinical research finds that the use of traditional Chinese medicine （TCM） has a positive effect on the treatment of hypoglycemia. Here the authors reviewed the current understanding of sensing and counterregulatory responses to hypoglycemia, and discuss combining traditional Chinese and Western medicine and the theory of iatrogenic hypoglycemia in diabetes treatment. Furthermore, the authors clarify the feasibility of treating hypoglycemia on the basis of TCM theory and CNS and have an insight on its clinical practice.     

Integrative techniques using acupuncture,Chinese herbal medicine,diet, and supplements for polycystic ovary syndrome： a case report

Patients with a diagnosis of polycystic ovary syndrome （PCOS） are on the rise. About 4%-12% of women are currently estimated to have this condition. It is hypothesized that PCOS appears in women who have long-standing insulin resistance （1R）, which leads to high androgen and testosterone levels; this ultimately disrupts their menstrual cycles. Some researchers attribute IR to genetic factors, although there have been only minute changes in the human genome in the past 20 000 years. However, even with a stable gene pool, genes can be turned on and offby the environment, food and air quality and toxin exposure.