Influenza viruses are common pathogens causing respiratory infections in humans. Among the four seasonal influenza viruses, influenza A virus H3N2 has become the leading cause of seasonal influenza illness and death, posing a great threat to public health and the economy. Since it first emerged and caused a pandemic in 1968, H3N2 has been circulating repeatedly in human beings and continually evades host immune attack by antigenic drift, resulting in a decrease in vaccine efficacy. In this paper, the antigenic evolution of influenza A virus H3N2, the impact of antigenic evolution on the selection of vaccine strains and some models for predicting the evolution of influenza viruses were analyzed and reviewed, which paved the road for understanding the antigenic evolution of influenza virus and vaccine development.

Influenza has caused high morbidity and mortality worldwide, seriously endangering human health and life. The continuous mutation of influenza virus has brought new challenges to the prevention and treatment of influenza. Animal models provide convenience for a comprehensive understanding of influenza virus pathogenesis, transmission mechanism, vaccine development, and evaluation of therapeutic effects. The construction and use of animal models of influenza virus infection vary in different studies, and the application of different animal models also has its own characteristics. This article reviewed the current status of the construction and use of various animal models, and summarized the advantages and limitations of animal models in evaluating the efficacy of antibodies, drugs and vaccines, with the aim of providing reference for the selection and optimization of animal models in the future.

Influenza viruses are responsible for a large number of infections and deaths annually, posing a serious threat to public health. Vaccination is the most effective measure to prevent influenza virus infection. However, current seasonal influenza vaccines only protect against closely matched circulating strains. Even with extensive surveillance and annual reformulation, yearly updated vaccines are still a step behind the fast-evolving viruses, often resulting in poor matches or less effective vaccines. Due to the relatively complex evolution of influenza A viruses, it is a new idea and a new means to prevent influenza epidemics by using a series of innovative technologies to develop universal influenza vaccines that can provide extensive and long-lasting protection against influenza viruses. This review summarized the latest progress in the development of universal vaccines targeting HA in the past three years, including design methods for universal vaccines targeting HA, HA stem and other conserved epitopes, compared the advantages and disadvantages of different technologies, explored the impact of immunization programs and strategies, and discussed the potential challenges to be overcome, hoping to provide reference for the successful development of universal vaccines.

Sepsis is a critical illness with high morbidity and mortality. Anaerobic glycolysis plays an important role in the pathogenesis of sepsis. Pyruvate dehydrogenase complex (PDHC) serves as a key regulator during sepsis. With PDHC dephosphorylation and deacetylation, PDHC activity is upregulated, allowing pyruvate translocate to mitochondria in aerobic condition, preceding the production of acetyl-CoA to accelerate aerobic oxidation. Activation of PDHC improves the prognosis of sepsis through regulating the balance of lactate, release of inflammatory factors and energy metabolism. A variety of remedies can improve the prognosis of patients with sepsis by up-regulating the activity of PDHC, including dichloroacetate (DCA), vitamin B1, milrinone, tumor necrosis factor binding protein, and ciprofloxacin.This article reviews the role and the regulatory mechanism of PDHC and signal pathway in the sepsis metabolism, in order to innovate treatment for sepsis and multiple organ dysfunction.

Cardiovascular diseases are life-threatening illnesses with high morbidity and mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic activity are involved in these diseases. Currently, pharmacological interventions primarily aim to inhibit over-excitation of sympathetic nerves, while vagal modulation has been largely neglected. Many studies have demonstrated that increased vagal activity reduces cardiovascular risk factors in both animal models and human patients. Therefore, the improvement of vagal activity may be an alternate approach for the treatment of cardiovascular diseases. However, drugs used for vagus nerve activation in cardiovascular diseases are limited in the clinic. In this review, we provide an overview of the potential drug targets for modulating vagal nerve activation, including muscarinic, and β-adrenergic receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and pyridostigmine) and the mechanism underlying their cardiovascular protective effects are also discussed.
Acetylcholine ; pharmacology ; Animals ; Cardiovascular Diseases ; drug therapy ; Cholinergic Agents ; therapeutic use ; Humans ; Receptors, Muscarinic ; drug effects ; Sympathetic Nervous System ; drug effects ; physiopathology ; Vagus Nerve ; drug effects ; physiopathology

Edong Healthcare Group is cited as an example to summarize its practice of centralized purchasing of supplies in the recent two years.In addition to a success in its process and mechanism, the authors analyzed some challenges for the purpose of furthering the group-based reform of public hospitals.

Objective To study the effects of dichloroacetate (DCA) on cell colony-forming,cell invasion and cell migration of the bladder cancer cells and to study the underlying mechanism.Methods The bldder cancer cells T24 were randomly divided into two groups:the observation group and the control group.Cells in the observation groups were treated with 5 mmol/L,10 mmol/L and 20 mmol/L dichloroacetate,and the control group was treated with the same amount of dimethyl sulfoxide.Colony formation assays were detected with Giemsa staining.Cell wound scratch assay and Transwell assay were applied to evaluate the ability of the T24 cell invasion and migration.Realtime PCR and Western blot were applied to detect the expression of the epithelial-mesenchymal transition (EMT)-related marker,including E-cadherin,N-cadherin,vimentin,Snail and Slug.Results Compared with the control group,the colony formation assays of T24 cells constantly decreased along with the increased doses in the observation group(P ＜ 0.01).The cell wound scratch assay showed that the scratch width of the observation groups were significantly higher along with the increased doses and prolonged time than that in the control group (P ＜ 0.01).The transwell assay showed that the invasion ability of the observation groups were significantly discreased along with the increased doses than that in the the control group (P ＜ 0.01).The expression levels of E-cadherin mRNA and protein in combination the control group were higher than those in the the observation groups (P ＜ 0.05).However,the expression levels of N-cadherin,vimentin,Snail and Slug mRNAs and proteins in combination the control group were lower than those in the the observation groups (P ＜ 0.05).Conclusion Dichloroacetate can inhibit the colony-forming,invasion and migration of bladder cancer T24 cells,and its mechanism may inhibit the expression of epithelial mesenchymal transition in T24 cells by down-regulating the expression of nuclear transcription factor Snail and Slug.

Objective: To investigate the presence of hepatitis E virus (HEV) RNA and HEV antigen (HEV-Ag) and to evaluate the infectivity of HEV in urine through a SPF rabbit model of HEV infection. Methods: Serum, fecal and urine samples collected from SPF rabbits with HEV infection were tested for viral and biochemical markers using real-time RT-PCR and ELISA. Liver and kidney biopsies were performed for observing histopathological changes and immunohistochemical staining. Rabbits were challenged with HEV isolated in urine samples to evaluate the infectivity. Results: Rabbit R1# that was injected with rabbit HEV presented viremia, fecal shedding of HEV, high serum level of HEV-Ag, elevated aspartate transaminase (AST) and alanine transaminase (ALT) and typical symptoms of hepatitis. Urine samples of rabbit R1# continued to be positive for HEV RNA and HEV-Ag. Ratios of HEV-Ag to RNA in urine samples of rabbit R1# were significantly higher than those in serum and feces samples. The parameters quantified in routine urinalysis remained within the normal ranges in rabbit R1#. However, pathological changes and the presence of HEV-Ag were observed in kidney tissues. Furthermore, serum and fecal samples that were collected from one of the two rabbits injected with rabbit R1# urine-derived HEV were HEV positive and the virus strains isolated form feces remained infective to rabbits. Conclusion HEV infection may result in kidney injury and the urine may pose a risk of transmission. HEV-Ag detection in urine may be valuable for the diagnosis of ongoing HEV infection.

Objective To analyze the practicability of using ELISA kit for the detection of hepati-tis E virus antigen ( HEV-Ag) in plasma donations and Biomex HEV seroconversion panels. Methods The HEV-Ag positive samples were screened out from 36 340 donated blood plasma samples. Real-time fluores-cent PCR was performed for the detection of HEV RNA in HEV-Ag positive samples. The open reading frame 2 (ORF2) in HEV RNA was amplified by nested RT-PCR and the amplified products were confirmed by sequencing analysis. Phylogenetic tree was constructed for HEV genotyping. Five Biomex HEV serocon-version panels were used in this study for the detection of HEV-Ag, anti-HEV antibody and HEV RNA as well as the correlation analysis between HEV-Ag and HEV RNA. Results Twenty-six out of 36 340 plasma samples (0. 07%) were positive for HEV-Ag. Of the 26 samples, 25 samples were positive for HEV RNA as indicated by the results of nested RT-PCR and 23 positive samples were confirmed by sequencing analysis. The positive rate of HEV RNA in blood plasma donators was 1 ∶ 1 580 (0. 06%). There were 17 samples of genotype 1 (74%) and 6 samples of genotype 4 (26%) according to the phylogenetic tree analysis. All of the HEV-Ag positive samples were also positive for HEV RNA as indicated by the analysis of Biomex sero-conversion panels. HEV-Ag was consistent with the peak of the HEV RNA concentration. Conclusion A close relationship between HEV-Ag and HEV RNA was observed. HEV-Ag screening could be used as a measure to reduce the risk of HEV transmission by blood transfusion.

Objective To establish a high throughput phenotypic test for the detection of drug re-sistance in human immunodeficiency virus(HIV)strains. Methods The gene encoding luciferase was in-activated through restriction enzyme digestion and ligation. LacZ gene was used to replace the genes encoding original protease and reverse transcriptase. pol genes were amplified from pSG3△env plasmid and cloned in-to a new backbone plasmid through infusion. The factors that might affect the results of the test were opti-mized. Results The parental backbone plasmid pNL4-3. Lac was constructed,of which the gene encoding luciferase was inactivated and bearing the LacZ gene instead of genes encoding protease and reverse tran-scriptase. Several influential factors including cell numbers(10 000 / well),virus inoculation(200 TCID50 /well)and the concentration of DEAE-dextran(15 μg/ ml)were optimized. The reproducibility of this test was confirmed by testing 12 anti-HIV drugs against 2 pseudovirus strains 8 times,presenting the coefficient of variations(CVs)from 4. 32% to 28. 46% . Six types of pseudovirus were constructed and tested against the 12 anti-HIV drugs,the results of which were compared with those by using the pSG3△env-based pseud-ovirus test. The results of the two tests presented good consistency. Conclusion The high throughput phe-notypic test based on pNL4-3. Lac plasmid,combining the advantages of pSG3△env and pNL4-3 systems, could be used to analyze the drug resistance patterns of HIV-1 infectors and screen new drugs for antiretrovi-ral therapy in a rapid and effective way.