Objective To discuss the relation between influenza peak, temperature and relative humidity. Methods Statistical analysis on the data of influenza consultation rates, temperature and relative humidity from 1998 to 2002 in Hong Kong area was carried out to propose some relation between influenza peak, temperature and relative humidity. Results It was slightly possible to cause influenza peak when the week-averaged temperature was less than 20 ℃ and largely possible to cause influenza peak when the week-averaged temperature was less than 15 ℃. It was also largely possible to cause influenza peak when the week-averaged temperature was very low and the relative humidity was higher which resulted the lower body-sense temperature compared with the forecasting temperature. Conclusion The prevalence of influenza occurs during four seasons in one year in Hong Kong, but the prevalence peak of influenza mainly appears under the condition of lower temperature(

Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Peripheral Blood Stem Cell Transplantation ; methods

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
Carcinoma ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Glucose ; metabolism ; Glycolysis ; Humans ; Malate Dehydrogenase ; metabolism ; NADP ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Oxidation-Reduction ; Oxidative Phosphorylation ; Pentose Phosphate Pathway ; Proto-Oncogene Proteins c-akt ; metabolism

OBJECTIVEA R1210C mutation of complement factor H (CFH) gene has been associated with age-related macular degeneration (AMD) in Caucasian population. This study was to verify above association in Han Chinese population.

METHODSThe mutation was detected by direct sequencing in 258 patients with wet AMD and 426 matched controls.

RESULTSThe R1210C mutation has not been identified in either sample.

CONCLUSIONThe R1210C mutation in CFH gene is not associated with AMD in Han Chinese population.

Aged ; Aged, 80 and over ; Complement Factor H ; genetics ; Female ; Humans ; Macular Degeneration ; genetics ; Male ; Middle Aged ; Mutation

OBJECTIVETo observe the intervention of Shenfu Injection (SFI) on the hemodynamics and circulatory function during induction of general anesthesia for aged people, in order to optimize the medication of anesthesia inductive phase in aged people.

METHODSSixty aged patients scheduled to receive general anesthesia were equally randomized into 2 groups, the SFI group and the control group. SFI via intravenous drip (1 mL/kg diluted with 5 mL/kg saline) was administered to the SFI group 15 min before anesthesia induction and to the control group, normal saline was administered instead. Then the induction and intubation were implemented. The systolic blood pressure (SBP), diastolic pressure (DBP), heart rate (HR), central venous pressure (CVP), pulse saturation oxygen (SpO2), and the ST segment of ECG were observed at the different time points of induction, i.e. at the time of entry into the operating room (T1), ending the medication (T2), before the induction (T3), showing the lowest SBP in induction (T4), before and after intubation (T5 and T5). The dose and frequency of atropine and ephedrine applied in the inductive phase were observed as well.

RESULTSAs compared with the baseline values measured at T1, CVP elevated at T2, T3, and T6 (P < 0.05), SBP and DBP descended at T4, T5, T6 in both groups; HR accelerated at T2, T3, and T6 in the control group; and HR at T4, T5 and T6 in both groups were significantly different (P < 0.05 or P < 0.01). Inter-group comparisons showed significant difference between groups in CVP at T2 (P < 0.05); so did SBP, DBP and HR at T4, T5 and T6 (P < 0.05 or P < 0.01).

CONCLUSIONApplication of SFI in the inductive phase of general anesthesia in aged people could evidently reduce the fluctuation of hemodynamics to prevent the occurrence of myocardial ischemia and improve it definitely.

Aged ; Anesthesia, Conduction ; Anesthesia, General ; Blood Circulation ; drug effects ; physiology ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Electrocardiography ; drug effects ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Humans ; Injections, Intravenous ; Male ; Myocardial Ischemia ; prevention & control ; Phytotherapy

The effect of arginine vasopressin (AVP) on membrane potential of neurons from dorsal root ganglion (DRG) was examined in the rat by means of intracellular recording technique. The results showed that (1) AVP induced hyperpolarization in the membrane of most DRG neurons. (2) The membrane conductance of the DRG neurons increased by 19.32% following application of AVP (p<0.05). (3) Perfusion with balance sodium solution (BSS) containing Cd(2+) (blocker of Ca(2+) channel) instead of Na+ failed to affect the AVP-induced membrane hyperpolarization of the DRG neurons (p> 0.05). After perfusion with BSS containing tetraethylammonium (TEA), however, the extent of AVP-induced hyperpolarization was reduced (p<0.05). (4) The AVP-induced hyperpolarization of the neurons was blocked by the antagonist of AVP V(1) receptors. The results demonstrate that AVP induces hyperpolarization of most DRG neurons, which might be caused by K(+) outflow mediated by AVP V(1) receptors in the membrane of the neurons.
Animals ; Arginine Vasopressin ; pharmacology ; Ganglia, Spinal ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; drug effects ; Rats ; Tetraethylammonium ; pharmacology

BACKGROUNDTo develop HPV16 L1/E6 and L1/E7 prophylactic and therapeutic DNA vaccines.

METHODSThe nucleotides within HPV 16 E6 and E7 genes, which are responsible for viral transforming activity, were mutated by mega primer site-directed mutagenesis method. The correctly mutated E6 and E7 fragments were separately cloned into an eukaryotic expression vector pVAX1, together with HPV 16 L1 gene, generating chimeric recombinants plasmids 1MpVAX1-L1E6, 2MpVAX1-L1E6, 1MpVAX1-L1E7, 2MpVAX1-L1E7 and 3MpVAX1-L1E7. CHO cells were transiently transfected with the individual DNA vaccines by calcium phosphate method. Target protein expressions in the extracts of the transfected cell lines were measured by ELISA and immunohistochemistry, with HPV 16 L1 and E6 specific monoclonal antibodies.

RESULTSELISA showed the P/N ratios in the cell extracts transfected with L1E6 and L1E7 plasmids were greater than 2.1. Immunohistochemistry revealed brownish precipitant signal in cytoplasm and nuclei of the transfected cells.

CONCLUSIONSSuccessful constructions of prophylactic and therapeutic DNA vaccine plasmids may be useful for future animal experiment and clinical trial.

Animals ; CHO Cells ; Capsid Proteins ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mutagenesis, Site-Directed ; Oncogene Proteins, Fusion ; biosynthesis ; immunology ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; immunology ; Papillomaviridae ; genetics ; Papillomavirus E7 Proteins ; Plasmids ; genetics ; Point Mutation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Repressor Proteins ; Transfection ; Vaccines, DNA ; biosynthesis ; genetics ; Viral Vaccines ; biosynthesis ; genetics

OBJECTIVETo investigate whether vascular endothelial growth factor (VEGF) gene plasmid carried by polytetrafluoroethylene (PTFE) vascular graft materials could transfect endothelial cells (ECs) and promote their growth.

METHODSPTFE vascular graft materials carried with pCDI-hVEGF(121), pCDI or pEGFP were incubated in Tris-buffer solution and the values of optical density of 260 nm at different time were plotted, then the DNA controlled release curve was made. ECs derived from human umbilical vein were seeded on the pCDI-hVEGF(121)/pCDI/pEGFP-PTFE materials or tissue culture plates, ECs numbers were counted and VEGF protein concentrations at different time were measured by enzyme-linked immunoadsorbent assay method. Green fluorescent protein (GFP) expression in ECs on pEGFP-PTFE materials was examined with fluorescence microscopy.

RESULTSThe controlled release curve showed that the gene released from PTFE materials was rapid within 8 h, then slowed down and that the gene released continuously even after 72 h. At 24, 72 and 120 h, ECs number and proliferation rate of pCDI-hVEGF(121)-PTFE materials were higher than those of pCDI or pEGFP-PTFE materials (P<0.05). VEGF protein concentration of pCDI-hVEGF(121)-PTFE materials was higher than that of pCDI or pEGFP-PTFE materials at 6, 24, 72 and 120 h (P<0.01). GFP expression in ECs on the pEGFP-PTFE materials could be detected by fluorescence microscopy.

CONCLUSIONPTFE graft can be used as a carrier of VEGF gene plasmid, VEGF gene carried by PTFE can transfect ECs and promote ECs growth.

Blood Vessel Prosthesis ; Cell Adhesion ; physiology ; Cell Growth Processes ; physiology ; DNA ; chemistry ; genetics ; Endothelial Cells ; cytology ; physiology ; Humans ; Plasmids ; chemistry ; genetics ; Polytetrafluoroethylene ; Transfection ; methods ; Vascular Endothelial Growth Factor A ; genetics

Bacteriophage lysin is characterized by high stability, wide bactericidal activity and efficacy, and safty. It is able to lyse bacteria specifically and is not susceptible to bacterial resistance. In the presence of phage, phage infecting bacteria and coding for endolysin then it lyse the bacteria, In the absence of the phage, holin assists the endolysin lysis the bacteria from external. In addition, the research progress on the treatment of Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus, Streptococcus pyogenes, and Gram-negative bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, was also discussed in this paper.