[Evaluation of the 10-year protective effect and immunogenicity of quadrivalent HPV vaccination].

Objective: To evaluate the 10-year protective effect and immunogenicity of quadrivalent human papillomavirus (HPV) vaccine in Chinese women aged 20 to 45 years. Methods: From October 2019 to April 2020, a long-term follow-up study was conducted on the subjects of the Phase III clinical trial of the quadrivalent HPV vaccine (NCT00834106). Participants underwent a questionnaire survey, venous blood sampling, gynecological examination, cervical exfoliated cell pathology examination, and serum neutralizing antibody titers for HPV-6, 11, 16, and 18 were measured using a pseudovirus neutralization assay. The results of the cytological examination and the positive rate and titers of serum antibodies of different cervical exfoliated cells were compared. Results: A total of 889 subjects were followed up, including 240 in the control group, 453 in the vaccination group and 196 in the post-trial vaccination group. The age of the control group was (40±7) years old, which was higher than that of the supplementary vaccination group and the vaccination group [(38±4) and (38±6) years old, respectively] (P<0.05). There were no statistically significant differences in condom use and sexual frequency among all groups (all P values>0.05). The abnormal proportion of cervical exfoliation cytopathology in the vaccination group was 3.7% (17/453), which was significantly lower than that in the control group [9.6% (23/240)] and post-trial vaccination group [5.6% (11/196)] (P<0.05). There were two cases of cervical intraepithelial neoplasia (CIN) grade 1 in the vaccination group, two cases of CIN grade 1 and three cases of CIN grade 2 and above in the control group, and no CIN grade 1 and above cases in the post-trial vaccination group. The positive rate of HPV-18 antibody was 35.5% (161/453) in the vaccination group and 76.0% (149/196) in the post-trial vaccination group, which was significantly lower than that of other types (P<0.05). The neutralizing antibody GMT ratio between the vaccination group and the control group ranged from 2.62 to 25.33 (9.05 to 83.08). Conclusion: Protective neutralizing antibodies are sustained in Chinese women aged 20 to 45 years after ten years of vaccination with quadrivalent HPV vaccine.

Ranitidine-induced anaphylaxis: clinical features, cross-reactivity, and skin testing.

BACKGROUND: Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine-induced anaphylaxis occurred in Korea from 2007 to 2014. OBJECTIVE: The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. METHODS: Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty-three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists. RESULTS: Over 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single-centre study, skin prick tests were positive in 91.7% of ranitidine-induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine-specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross-reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re-experienced the same adverse reactions because ranitidine was not considered the culprit drug. CONCLUSIONS AND CLINICAL RELEVANCE: Although ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis.

Measles: old vaccines, new vaccines.

Isolation of measles virus in tissue culture by Enders and colleagues in the 1960s led to the development of the first measles vaccines. An inactivated vaccine provided only short-term protection and induced poor T cell responses and antibody that did not undergo affinity maturation. The response to this vaccine primed for atypical measles, a more severe form of measles, and was withdrawn. A live attenuated virus vaccine has been highly successful in protection from measles and in elimination of endemic measles virus transmission with the use of two doses. This vaccine is administered by injection between 9 and 15 months of age. Measles control would be facilitated if infants could be immunized at a younger age, if the vaccine were thermostable, and if delivery did not require a needle and syringe. To these ends, new vaccines are under development using macaques as an animal model and various combinations of the H, F, and N viral proteins. Promising studies have been reported using DNA vaccines, subunit vaccines, and virus-vectored vaccines.

Observation of a spontaneous particle-transport barrier in the HL-2A tokamak.

Using the profile analysis, the density perturbation transport analysis, and the Doppler reflectometry measurement, for the first time a spontaneous and steady-state particle-transport barrier has been evidenced in the Ohmic plasmas in the HL-2A tokamak with no externally applied momentum or particle input except the gas puffing. A threshold in density has been found for the observation of the barrier. The particle diffusivity is well-like, and the convection is found to be inward outside the well and outward inside the well. The formation of the barrier coincides with the transition between the trapped electron mode and the ion temperature gradient driven mode.

Materials: tribology experiment in zero gravity.

A tribology experiment in zero gravity was performed during the orbital flight of Spacelab 1 to study the motion of liquid lubricants over solid surfaces. The absence of a significant gravitational force facilitates studies of the motion of liquid lubricants over solid surfaces as controlled by interfacial and capillary forces. Observations were made of phenomena associated with the liquid on one solid surface and also with the liquid between a pair of closely spaced surfaces. Typical photographic records obtained on Spacelab 1 are described.

LncRNA MAFG-AS1 promotes the aggressiveness of breast carcinoma through regulating miR-339-5p/MMP15.

OBJECTIVE: The main purposes of this study are to investigate the possible effects of long noncoding RNAs (lncRNAs) MAFG-AS1 on the growth and metastasis of breast carcinoma. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay was used to assess the MAFG-AS1 level in breast cancer tissues and cells. The wound healing and transwell invasion analysis were applied to explore the invasion and migration of breast cancer cell in vitro. The expressions of epithelial-mesenchymal transition (EMT) related markers were determined by Western blotting. Xenograft model and lung metastasis model were used to assess the progression of breast carcinoma cell in vivo. RESULTS: The level of lncRNA MAFG-AS1 is higher in breast carcinoma, and the aggressive phenotypes of breast carcinoma cell are enhanced by MAFG-AS1 transfection. Moreover, we identify that MAFG-AS1 overexpression reduces the expression of miR-339-5p and miR-339-5p is the target of MAFG-AS1 in breast carcinoma. In addition, matrix metalloproteinase 15 (MMP15) is the functional regulated gene of miR-339-5p in breast carcinoma. The aggressiveness of breast carcinoma induced by lncRNA MAFG-AS1 is weakened by the miR-339-5p. Finally, we demonstrated that the development of breast carcinoma cell is enhanced by MAFG-AS1 in vivo. CONCLUSIONS: MAFG-AS1 appears to play an oncogene role in breast carcinoma by regulating the miR-339-5p/MMP15.

Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants.

OBJECTIVES: To assess internal dose and oxidative stress in male restaurant workers exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking oil fumes (COFs) in Chinese restaurants. METHODS: The study participants included 288 male restaurant workers (171 kitchen and 117 service staff) in Chinese restaurants in Taiwan. Airborne particulate PAHs were measured over 12 h on each of two consecutive work days and then identified using high performance liquid chromatography. Urinary 1-hydroxypyrene (1-OHP) measurements were used to indicate COF exposure, and urinary malondialdehyde (MDA) was adopted as an oxidative stress marker. Multiple regression models were used to assess the relationship between MDA and 1-OHP levels after adjusting for key personal covariates. RESULTS: Summed particulate PAH levels in kitchens (median 23.9 ng/m(3)) were significantly higher than those in dining areas (median 4.9 ng/m(3)). For non-smoking kitchen staff, mean MDA and 1-OHP levels were 344.2 (SD 243.7) and 6.0 (SD 8.0) mumol/mol creatinine, respectively. These levels were significantly higher than those for non-smoking service staff, which were 244.2 (SD 164.4) and 2.4 (SD 4.3) mumol/mol creatinine, respectively. Urinary 1-OHP levels were significantly associated with work in kitchens (p<0.05). Furthermore, urinary MDA levels were significantly associated with urinary 1-OHP levels (p<0.001) and working hours per day (p<0.05). CONCLUSIONS: These findings indicate that urinary 1-OHP and MDA levels reflect occupational exposure to PAHs from COFs and oxidative stress in workers in Chinese restaurants.

Cancer incidence in young and middle-aged people with schizophrenia: nationwide cohort study in Taiwan, 2000-2010.

AIMS: For nearly a century, the incidence of cancer in people with schizophrenia was lower than in the general population. In the recent decade, the relationship between cancer and schizophrenia has become obscured. Thus, we investigated the cancer risk among young and middle-aged patients with schizophrenia. METHODS: Records of newly admitted patients with schizophrenia (n = 32 731) from January 2000 through December 2008 were retrieved from the Psychiatric Inpatient Medical Claims database in Taiwan, and the first psychiatric admission of each patient during the same period was defined as the baseline. We obtained 514 incident cancer cases that were monitored until December 2010. Standardised incidence ratios (SIRs) were calculated to compare the risk of cancer between those with schizophrenia and the general population. Stratified analyses of cancer incidences were performed by gender, site of cancers and duration since baseline (first psychiatric admission). RESULTS: The incidence of cancer for all sites was slightly higher than that of the general population for the period (SIR = 1.15 [95% CI 1.06-1.26], p = 0.001). Men had a significantly higher incidence of colorectal cancer (SIR = 1.48 [95% CI 1.06-2.06], p = 0.019). Women had a higher incidence of breast cancer (SIR = 1.47 [95% CI 1.22-1.78], p < 0.001). Intriguingly, the risk for colorectal cancer was more pronounced 5 years after the first psychiatric admission rather than earlier (SIR = 1.94 [1.36-2.75], p < 0.001) and so was the risk for breast cancer (SIR = 1.85 [1.38-2.48], p < 0.001). The cancer incidence was higher in patients with schizophrenia contradicting the belief that schizophrenia was protective of cancers. CONCLUSIONS: Our analyses suggest that men and women with schizophrenia were more vulnerable to certain types of cancers, which indicates the need for gender-specific cancer screening programs. The fact that risk of colorectal cancer was more pronounced 5 years after the first psychiatric admission could imply the impact of unhealthy lifestyles or the possibility of delayed diagnoses.

A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor beta-arrested epithelial cells.

Transforming growth factor beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play a role in the G1-to-S phase transition in mammalian cells. We have studied the effects of TGF-beta-mediated growth arrest on G1/S cyclins E and A. Inhibition of cyclin A-associated kinase by TGF-beta is primarily due to a decrease in cyclin A mRNA and protein. By contrast, while TGF-beta inhibits accumulation of cyclin E mRNA, the reduction in cyclin E protein is minimal. Instead, we find that the activation of cyclin E-associated kinase that normally accompanies the G1-to-S phase transition is inhibited. A novel inhibitor of cyclin-Cdk complexes was detected in TGF-beta-treated cell lysates. Inhibition is mediated by a heat-stable protein that targets both Cdk2 and Cdc2 kinases. In G0-arrested cells, a similar inhibitor of Cdk2 kinase was detected. These data suggest the existence of an inhibitor of cyclin-dependent kinases induced under different conditions to mediate antiproliferative responses.

Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited.

Molecular epidemiological studies on foot-and-mouth disease type O Taiwan viruses from the 1997 epidemic.

Sequence diversity was assessed of the complete VP1 gene directly amplified from 49 clinical specimens during an explosive foot-and-mouth disease (FMD) outbreak in Taiwan. Type O Taiwan FMD viruses are genetically highly homogenous, as seen by the minute divergence of 0.2-0.9% revealed in 20 variants. The O/HCP-0314/TW/97 and O/TCP-022/TW/97 viral variants dominated FMD outbreaks and were prevalent in most affected pig-raising areas. Comparison of deduced amino acid sequences around the main neutralizable antigenic sites on the VP1 polypeptide showed no significant antigenic variation. However, the O/CHP-158/TW/97 variant had an alternative critical residue at position 43 in antigenic site 3, which may be due to selective pressure in the field. Two vaccine production strains (O1/Manisa/Turkey/69 and O1/Campos/Brazil/71) probably provide partial heterologous protection of swine against O Taiwan viruses. The type O Taiwan variants clustered in sublineage A1 of four main lineages in the phylogenetic tree. The O/Hong Kong/9/94 and O/1685/Moscow/Russia/95 viruses in sublineage A2 are closely related to the O Taiwan variants. The causative agent for the 1997 epidemic presumably originated from a single common source of type O FMD viruses prevalent in neighboring areas.

Isolation and Characterization of Basic Exochitinase from Leaf Extract of Rehmannia glutinosa.

Rehmannia chitinases were extracted from the leaves of Rehmannia glutinosa under acidic conditions (pH 2.9). We purified a 28.6-kDa chitinase, designated as P2, from crude extract to homogeneity by (NH4)2SO4 precipitation, chromatography with regenerated chitin affinity and hydrophobic interaction column, and preparative native PAGE. Isolated P2 showed maximum chitinase activity at pH 5.0 and 60°C, and had a isoelectric point of 8.46. P2 produced only (GlcNAc)2 from (GlcNAc)4-6 and regenerated chitin. Based on these results, we arrived at the conclusion that P2 was a basic exochitinase.

Actinoidin A2, a novel glycopeptide: production, preparative HPLC separation and characterization.

An unidentified Nocardia sp. (SK&F-AAJ-193) was isolated and found to produce actinoidin A and a novel analog which we have named actinoidin A2. This new glycopeptide antibiotic differs from actinoidin A by the presence of rhamnose instead of acosamine. This analog was isolated using Dianion HP-20 resin followed by a specific glycopeptide affinity column (Affigel-10-D-Ala-D-Ala). The purification was accomplished using preparative ion-pairing chromatography. Actinoidin A2 is active against Staphylococcus aureus and coagulase-negative Staphylococci although it is less potent than actinoidin A.

Chlorocardicin, a monocyclic beta-lactam from a Streptomyces sp. I. Discovery, production and biological activities.

Chlorocardicin is a new monocyclic beta-lactam produced by a Streptomyces sp. It is structurally related to nocardicin A but differs in having a m-chloro substituent on the p-hydroxyphenylglycine unit. The biological activity of chlorocardicin was similar to nocardicin A but the former showed less antagonism in complex media. Moderate in vitro activity was observed against Enterobacteriaceae and Pseudomonas aeruginosa. Chlorocardicin showed low activity against Staphylococcus aureus whereas nocardicin A was inactive. Both compounds were shown to be strongly potentiated by antibiotics that inhibit peptidoglycan biosynthesis and were antagonized by selected L- and D-amino acids.

Aridicins, novel glycopeptide antibiotics. I. Taxonomy, production and biological activity.

A new species of a new genus of the Actinomycetales was discovered, Kibdelosporangium aridum. This strain produces a new family of glycopeptide antibiotics designated aridicins, that contain an unusual glycolipid constituent. They inhibit Gram-positive bacteria, including staphylococci, enterococci and Clostridium sp.

Kibdelins, novel glycopeptide antibiotics. I. Discovery, production, and biological evaluation.

A new subspecies of Kibdelosporangium aridum subsp. largum (SK&F AAD-609), was isolated and shown to produce novel glycopeptides related to aridicins, but containing a homologous series of glycolipids based on N-acylglucosamine. These compounds showed improvements over the aridicins in in vitro activity and were effective in mouse protection studies against a range of Gram-positive bacteria, including methicillin resistant staphylococci. Pharmacokinetic studies indicated that they have high serum concentrations and long-acting potential. The kibdelin complex modified rumen metabolism in a manner favorable for growth promotion.

Modulation of immune responses to DNA vaccines by codelivery of cytokine genes.

DNA vaccines containing genes for antigenic portions of viruses have recently been developed as a novel vaccination technology. Direct injection of plasmid DNA in vivo results in prolonged expression of viral proteins and may, thus, mimic the action of attenuated vaccines. An important advantage of this vaccination method is that in vivo-synthesized viral proteins can enter both major histocompatibility complex (MHC) class I and class II antigen-processing pathways to activate specific immunization. In many animal models for infectious diseases, DNA vaccines induced a broad range of immune responses, including antibody, CD8+ cytotoxic T lymphocytes (CTL) and CD4+ helper T (Th) lymphocyte responses, and protective immunity against challenge with the pathogen. The magnitude and nature of these immune responses to DNA vaccines can be further manipulated by codelivery of cytokine genes. Summarizing the many studies reported to date, we can draw conclusions regarding the adjuvant effects of these cytokine genes on DNA vaccines. Coadministration of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-2 genes induces higher antibody titers and T-cell proliferation responses than other cytokine genes tested to date. In contrast, the CTL activity is only modestly increased by the GM-CSF and IL-2 genes. The IL-12 gene polarizes the immune responses to DNA vaccines toward Th1 cell development and stimulates the strongest CTL activity. In contrast, co-injection of the IL-4 gene promotes the development of Th2 cells and increases production of antibodies, but suppresses CTL activity. Thus, the immune responses to DNA vaccines can be engineered by co-injection of an appropriate cytokine gene to favor the formation of either CTL or neutralization antibodies and, therefore, provide the best protection against a particular pathogen.

Outcomes of nerve reconstruction for radial nerve injuries based on the level of injury in 244 operative cases.

We report a single surgeon series of 244 patients with radial nerve injuries who had nerve repair, neurolysis, or nerve graft over a 17-year period. 44 patients had a Level I or infraclavicular injury, 37 had a Level II injury within the spiral groove of the humerus, 104 had a Level III injury from the lateral arm to antebrachial fossa and 64 had a Level IV injury affecting the posterior interosseous nerve. Nerve grafting was used most frequently in all groups, and was the only method of reconstruction for level II injury. At 21.5 months follow up, Level IV injuries had significantly better outcome of finger and thumb extension, while wrist extension recovered in at least 80% of the patients irrespective of the level of injury. The radial nerve recovered better if repaired or reconstructed within 5 months of injury.

Measurements of the fast electron bremsstrahlung emission during electron cyclotron resonance heating in the HL-2A tokamak.

A fast electron bremsstrahlung (FEB) diagnostic technique based on cadmium telluride (CdTe) detector has been developed recently in the HL-2A tokamak for measurements of the temporal evolution of FEB emission in the energy range of 10-200 keV. With a perpendicular viewing into the plasma on the equatorial plane, the hard x-ray spectra with eight different energy channels are measured. The discrimination of the spectra is implemented by an accurate spectrometry. The system also makes use of fast digitization and software signal processing technology. An ambient environment of neutrons, gammas, and magnetic disturbance requires careful shielding. During electron cyclotron resonance heating, the generation of fast electrons and the oscillations of electron fishbone (e-fishbone) have been found. Using the FEB measurement system, it has been experimentally identified that the mode strongly correlates with the electron cyclotron resonance heating produced fast electrons with 30-70 keV.

A method of particle transport study using supersonic molecular beam injection and microwave reflectometry on HL-2A tokamak.

A method of the particle transport study using supersonic molecular beam injection (SMBI) and microwave reflectometry is reported in this paper. Experimental results confirm that pulsed SMBI is a good perturbation source with deeper penetration and better localization than the standard gas puffing. The local density modulation is induced using the pulsed SMBI and the perturbation density is measured by the microwave reflectometry. Using Fourier transform analysis for the local density perturbation, radial profiles of the amplitude and phase of the density modulation can be obtained. The experimental results in HL-2A show that the particle injected by SMBI is located at about r/a=0.65-0.75. The position of the main particle source can be determined through three aspects: the minimum of the phase of the first harmonic of the Fourier transform of the modulated density measured by microwave reflectometry; the H(a) intensity profile and the local density increase ratio. The maximum of the amplitude of the first harmonic shifts often inward relative to the particle source location, which indicates clearly there is an inward particle pinch in this area. Good agreement has been found between the experimental results and the simulation using analytical transport model. The particle diffusivity D and the particle convection velocity V have been obtained by doing this simulation. The sensitivity in the transport coefficients of the amplitude and the phase of the density modulation has been discussed.