[Sensitization characteristics of Juniperus chinensis pollen in Beijing area].

Objective: To investigate the sensitization characteristics of Juniperus chinensis pollen in patients with allergic rhinitis and/or allergic asthma in Beijing area, and to explore the characteristics of Juniper chinensis pollen sensitized population. Methods: Patients with suspected allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were selected in this study. Skin prick test (SPT) was performed with Juniper chinensis pollen allergen reagent to compare different age and disease allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results: A total of 8 380 patients were enrolled in the end. The total positive rate of Juniper chinensis pollen SPT reached 49.92% (4 183/8 380). The positive rate of Juniper chinensis pollen SPT was highest in the 10-14 age group, reaching 60.99% (283/464). Compared with other age groups, there was a statistical difference (χ²=266.77, P<0.01). The SPT positive rate of patients aged less than 10 years increased with the increase of age, while the SPT positive rate of patients aged over 40 years decreased with the increase of age. Single Juniper chinensis pollen was less allergenic, accounting for about 25.05% (1 048/4 183), and the patients' age was (35.21±12.39) years. Regardless of single Juniper chinensis pollen or other pollen allergies, allergic rhinitis was the main disease. Among the patients with SPT positive Juniper chinensis pollen combined with other inhaled pollen allergens, willow pollen accounted for the first (74.99%). The positive rate of Juniper chinensis pollen was the highest in patients with single allergic rhinitis, accounting for 52.05% (3 797/7 295), and the rate in patients with single allergic asthma was the lowest, accounting for 17.49% (53/303), with statistically difference (χ²=138.99, P<0.01). Conclusions: Juniper chinensis pollen is highly sensitized in patients with allergic rhinitis and/or allergic asthma in Beijing . The positive rate of SPT is highest among 10-14 age group, most of which showed strong positive reaction, and allergic rhinitis is more common in Juniper chinensis pollen sensitization diseases.

[Gene expression profile analysis involved in pathogenesis of allergic rhinitis by using bioinformatics method as a novel way of drug screening].

Objective: To analyze the dynamic changes of the clinical features of chronic rhinosinusitis in recent 10 years, so as to deeply understand the characteristics of chronic rhinosinusitis, and to provide new ideas for treatment of chronic rhinosinusitis. Method: This retrospective study was performed in patients who were diagnosed as chronic rhinosinusitis and enrolled. General information, clinical examination and pathological results were all collected, then patients' age, gender, the incidence of asthma and allergic rhinitis, peripheral eosinophil percentage, olfactory dysfunction and pathological results were statistically analyzed. Result: 1 955 patients who were diagnosed as chronic rhinosinusitis(CRS) were enrolled in this study, including 570 patients in 2006, 583 patients in 2010, and 802 patients in 2015. There were no obvious changes of age structure in these patients in three years. And there was no significant change in sex ratio as well. The proportions of patients with CRS concomitant with asthma were obviously increased in 10 years, which was 3.51% in 2006, 7.55% in 2010, and 17.58% in 2015. The proportions of patients with allergic rhinitis were also increased, which was 10.35% in 2006, 8.75% in 2010, and 14.09% in 2015. Peripheral eosinophil ratio was increased significantly in these patients after 2010. The proportions of ECRS in CRS were elevated in 2015 and almost doubled compared to 2006. Olfactory dysfunction increased significantly in 2015. Conclusion: In recent 10 years, there were obvious changes of clinical features of CRS. The proportion of patients with CRS concomitant with asthma showed a gradual increasing trend. ECRS significantly increased than it was 10 years ago. Olfactory dysfunction also increased significantly. In order to improve the therapeutic effect of CRS, it is necessary to strengthen the treatment of upper and lower airway inflammation related with eosinophil.

[Observation on pollinosis with vegetable food allergy].

Objective: To investigate the incidence of plant food allergy in patients with pollinosis and the effect of food allergens on the clinical symptoms of pollinosis patients. Method: A total of 40 patients with pollinosis and food allergy attended to the allergy Department of Duolun People's Hospital of Inner Mongolia were accepted skin prick test of inhaled allergens while the rhino conjunctivitis quality of life questionnaire(RQLQ) were also completed. The patients were divided into A and B groups randomly. Patients in group A were required for avoiding allergic plant foods intake but not them in group B. The two groups of patients with RQLQ, VAS and clinical symptom scores were statistically analyzed by P<0.05, the difference was statistically significant. Result: Forty cases were allergic to Artemisia. The most common allergic plant foods was peach, which accounted for 47.5%. Twenty-four patients were allergic to multiple foods simultaneously. Seventeen cases of pollinosis were preceded by food allergy, and 23 cases of food allergy were preceded by pollinosis. The mean values of RQLQ, VAS and symptom scores in group A were 81.44±14.31, 6.02±1.39, 10.60±3.68, respectively. The mean values of group B patients after 1 years were 100.73±21.66, 8.30±1.00, 13.45±3.51, the difference was statistically significant (P<0.01). The patients in group A complained that the symptoms were better than before. The mean values of RQLQ, VAS and symptom scores before intervention were 105.2±26.69, 7.00±1.71, 14.83±3.66, with significant difference (P<0.01). There was no significant improvement in the symptoms of Group B patients (P>0.05). Conclusion: Patients with pollinosis are often associated with food allergies. Reducing the intake of allergic plant foods should help alleviate symptoms.

[Clinical observation on specific immunotherapy of allergic rhinitis with artemisia pollen].

Objective:The aim of this study is to observe the clinical efficacy of pollen specific immunotherapy with Artemisia in allergic rhinitis. Method:A total of 139 patients with allergic rhinitis who were positive for Artemisia pollen were selected for allergen skin pricking. All of them were treated with Artemisia pollen-specific immunotherapy. The patients were followed-up for 3 months, respectively before treatment (N), after treatment start interval. 3 months (D1, D2, D3) followup fill in the total score of nasal symptoms (TNSS), visual analogue scale (VAS) score, olfactory function grading, ocular symptom score (TOSS) and rhinoconjunctivitis quality of life questionnaire (RQLQ) )score. Result:TNSS：N>D1，N>D2，N>D3，D1,D2,D3 two of the three compared to no difference.VAS：N>D1，N>D2，N>D3，among D1,D2,D3, two of the three compared to no difference. Olfactory function classification:N>D1，N>D2，N>D3，among D1,D2,D3, two of the three compared to no difference.TOSS：N>D1，N>D2，N>D3，among D1,D2,D3,D1>D2,the rest had no difference. RQLQ: N>D1, N>D2, N>D3, D1>D2, D3>D1, D3>D2. Conclusion:The specific pollen immunotherapy of artemisia is effective in the treatment of allergic rhinitis, and the symptoms are obviously improved.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

Evolution of Sulfobacillus thermosulfidooxidans secreting alginate during bioleaching of chalcopyrite concentrate.

AIMS: To explore the distribution disciplinarian of alginate on the chalcopyrite concentrate surface during bioleaching. METHODS AND RESULTS: The evolution of Sulfobacillus thermosulfidooxidans secreting alginate during bioleaching of chalcopyrite concentrate was investigated through gas chromatography coupled with mass spectrometry (GC-MS) and confocal laser scanning microscope (CLSM), and the critical synthetic genes (algA, algC, algD) of alginate were analysed by real-time polymerase chain reaction (RT-PCR). The GC-MS analysis results indicated that there was a little amount of alginate formed on the mineral surface at the early stage, while increasing largely to the maximum value at the intermediate stage, and then kept a stable value at the end stage. The CLSM analysis of chalcopyrite slice showed the same variation trend of alginate content on the mineral surface. Furthermore, the RT-PCR results showed that during the early stage of bioleaching, the expressions of the algA, algC and the algD genes were all overexpressed. However, at the final stage, the algD gene expression decreased in a large scale, and the algA and algC decreased slightly. This expression pattern was attributed to the fact that algA and algC genes were involved in several biosynthesis reactions, but the algD gene only participated in the alginate biosynthesis and this was considered as the key gene to control alginate synthesis. CONCLUSIONS: The content of alginate on the mineral surface increased largely at the beginning of bioleaching, and remained stable at the end of bioleaching due to the restriction of algD gene expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings provide valuable information to explore the relationship between alginate formation and bioleaching of chalcopyrite.

Lack of response to multiple genotoxic agents at the hprt locus in peripheral blood T-lymphocytes of cynomolgus monkeys.

We tested the ability of a series of known genotoxic agents to cause mutations at the hprt locus in peripheral blood T-lymphocytes of cynomolgus monkeys as measured by the ability to form clones in the presence of 6-thioguanine. Ethylmethane sulfonate (EMS, 300 mg/kg i.p.), chloroethylmethane sulfonate (CI-EMS, 35 or 50 mg/kg i.p.), and the Pharmacia & Upjohn antitumor agents adozelesin (1.6, 4, 6, or 8 microg/kg i.v.) and CC-1065 (6 microg/kg i.v.) were all negative in the hprt mutation test. Results with cyclophosphamide (CP, 75 mg/kg i.v.) were equivocal. Adozelesin, CC-1065, and CI-EMS treatments increased the percentage of T-lymphocytes with chromosome aberrations, as well as inducing types of aberrations not seen in control cells. EMS and CP were not tested for chromosome aberrations. We have previously shown that treatment of monkeys with 77 mg/kg ENU substantially increased the hprt mutant frequency, with a lag time of approximately 77 days between treatment and peak MF values. The results of the present study suggest a low sensitivity of the hprt mutation assay to certain classes of genotoxic agents in cynomolgus monkeys.

Antiendotoxin strategies for the prevention and treatment of septic shock. New approaches and future directions.

Therapy for Gram-negative sepsis remains unsatisfactory despite a concerted effort to develop new treatments for this common, life-threatening syndrome. Current research continues on several fronts to improve the treatment options available to clinicians in the management of these critically ill patients. Recently, a greater understanding of the complex molecular basis of endotoxin-mediated pathophysiological effects in humans has generated a number of novel therapeutic agents for sepsis. Several of these treatment strategies have already entered clinical trials and it is hoped that some of these therapies will become widely available in the near future. In this review, the current status of the most promising new antiendotoxin agents is summarised, and the major obstacles to the successful clinical development of these therapies are described. New antiendotoxin therapies include those which interrupt the synthesis of endotoxin, bind and neutralise its activity, prevent endotoxin interactions with host effector cells and interfere with endotoxin-mediated signal transduction pathways. Potential therapeutic strategies involving these agents consist of endotoxin analogues, antibodies, subunit vaccines, binding columns, recombinant human proteins and small molecule inhibitors of endotoxin synthesis and intracellular signalling. The pitfalls of previous antiendotoxin clinical investigations and the perils of future clinical trial designs are discussed in the context of unmet needs and realistic expectations for success. While considerable progress has been made, effective and new treatments for Gram-negative bacterial sepsis continues to elude us at the present time. This has been to the detriment of patients, investigators and pharmaceutical companies alike. It will require focused efforts by basic scientists, continued support by industry and enlightened study designs by clinical investigators to successfully develop antiendotoxin in therapies for use in septic patients in the future.

End points for biomonitoring: assay sensitivity/selectivity.

Estimation of population exposure and biological impact of potential hazards are central reasons for performing biomonitoring. The sensitivity of the biomonitoring methods and the linkage of the measured phenomenon to human disease are also important, but often overlooked, considerations. We are conducting experiments to evaluate the sensitivity of hprt mutation measurement in the nonhuman primate, the cynomolgus monkey. Our findings demonstrate in the monkey that hypoxanthine guanine phosphoribosyltransferase (hprt) mutations produced in vivo can be detected using technique originally worked out using human cells; cynomolgus monkeys were chosen to avoid many of the complications encountered in studying humans. Sequencing of mutants from the monkey using reverse transcriptase polymerase chain reaction methods has led us to conclude that there is similarity of the spectra observed between the spontaneous mutations detected in the two species. However, more recent data suggest that due to low sensitivity, the method is probably not appropriate for routine biomonitoring of randomly selected populations. For example, the inability of the hprt mutation assay to detect some very potent mutagens in the monkey and the effects of the time-dependent pattern of mutant occurrence serve to urge caution in interpretation of elevation or lack of elevation in mutant frequency. Mechanisms for splitting and archiving samples of human tissues/blood from populations at risk may prove valuable as methods improve.

Lung tumor induction in A/J mice and clastogenic effects in CD-1 mice of the sequence-selective DNA alkylating agents (+)-CC-1065 and (-)-CC-1065.

The in vivo genotoxic effects of the antitumor antibiotic, (+)-CC-1065, and its unnatural enantiomer, (-)-CC-1065, were investigated in two mouse models. These two compounds alkylate AT-rich regions of double stranded DNA with distinct sequence selectivities. (+)-CC-1065 dose-dependently increased the chromosomal aberration frequency in bone marrow cells of CD-1 mice from 1.2 +/- 0.8% in vehicle control animals to 5.0 +/- 1.2%, 11.4 +/- 3.9%, and 20.6 +/- 2.3% 24 hours following single intravenous doses of 2, 4, and 8 micrograms/kg, respectively. (-)-CC-1065 was significantly less potent with a maximal response at 8 micrograms/kg approximately one-third of that observed for (+)-CC-1065. (+)-CC-1065 induced a significant (P < or = 0.05), three-fold increase in the number of lung tumors/mouse in strain A/J mice from 0.27 +/- 0.15 for vehicle control animals to 0.83 +/- 0.15 24 weeks following a single intravenous dose of 8 micrograms/kg. This effect was paralleled by corresponding threefold increases in the percentage of mice with tumors and the percentage of mice with multiple tumors, compared to vehicle controls. (-)-CC-1065 at 8 micrograms/kg induced 0.67 +/- 0.15 tumors/mouse and resulted in slightly smaller increases in the tumor incidence and multiple tumor incidence, compared to (+)-CC-1065. The above results demonstrate that single intravenous doses of (+)- CC-1065 and (-)-CC-1065 which cause chromosomal damage in CD-1 mice also induce an increased incidence of lung tumors in A/J mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Micronuclei in mice treated with monocrotaline with and without phenobarbital pretreatment.

Monocrotaline is a very potent toxin, producing significant effects of pneumotoxicity, hepatotoxicity, and teratogenicity, as well as carcinogenicity. In addition, the compound has been clearly shown to be mutagenic after metabolic activation. The goal of the experiments reported here was to confirm the reported clastogenesis induced by this agent in vivo and to evaluate the impact of modulation of metabolic activity by phenobarbital, a potent P-450 inducer (both Phase I and Phase II enzymes). The method used in addressing this problem relied on a new technique for monitoring clastogenesis in vivo, i.e., the acridine orange micronucleus assay method originally exploited by Hayashi et al. [1990]. The result of our experiments confirmed monocrotaline to be an effective clastogen in vivo, using the acridine orange method of assessment. The peak in induction of micronuclei occurred on the second day following intraperitoneal administration of the drug. Administration of phenobarbital prior to monocrotaline did appear to modulate the micronucleus induction. At 30 mg/kg bw monocrotaline, the pretreatment with phenobarbital appears to increase the intensity of monocrotaline clastogenesis, while the effect at higher doses (60 and 125 mg/kg bw) is a reduction in potency, presumably reflecting increased importance of Phase II metabolism for monocrotaline at these doses. Thus the study reported here confirms the potent in vivo clastogenesis of monocrotaline, and provides evidence for a dose-related shift in mechanism for the phenomenon.

Risk and benefit evaluation in development of pharmaceutical products.

Pharmaceutical products are intended to cure disease, reduce pain and suffering, prolong life, and correct metabolic deficits in patients. However, the potential patient population is intrinsically genetically heterogenous, and this factor complicates the evaluation of data on all aspects of safety evaluation of new drugs. Often the genetic heterogeneity is related to drug metabolizing capacity, but recent evidence suggests that heterogeneity in repair capacity as well as structural integrity of the chromatin (fragile X) have been shown to be relevant. Because drugs are biologically active and may have more than one type of effect, the evaluation of a large number of parameters is necessary in arriving at a rational estimate of potential risk. In this paper, several specific examples of risk assessments and some generic genotoxicity questions that are recurrent, including the question of the relevance of in vitro chromosomal aberration induction at high dose/sampling time, are raised. Other examples of the kinds of concerns from the safety evaluation of U-48753E, U-54461, and U-68,553B are discussed. The drug U-48753E was discovered to be slightly mutagenic in the AS52 assay, and significant efforts were expended in evaluation of the metabolism-based generation of a reactive intermediate. The drug U-54,461 was shown to be capable of breaking chromosomes in vitro but extensive in vivo data as well as a variety of other studies served to reduce the level of concern substantially.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomal breakage following treatment of CHO-K1 cells in vitro with U-68,553B is due to induction of undercondensation of heterochromatin.

Preferential breakage of chromosomes at specific sites (so-called "fragile sites") has been observed to occur spontaneously, and has been induced by some metal salts and chemicals. Furthermore, a heterochromatic region of the long arm of the Chinese hamster ovary (CHO) X-chromosome is known to be susceptible to a disproportionately high frequency of spontaneous breakage; unless there is physical displacement of chromatin the resulting achromatic lesions are not scored as structural aberrations. We have encountered such anomalous breakage associated with C-band positive regions of the chromosomes of a CHO-K1 cell line following exposure of the cells to toxic doses of U-68,553B and in this report present evidence that the apparent breaks are due to undercondensed heterochromatin (UH) and evidence that the phenomenon appears to occur at higher frequency in a particular cell line of Chinese hamster. This finding has important implications on the assessment of potential risk due to exposure to the drug. Such apparent breaks at sites of UH in chromosome 1 was not observed in an alternate CHO cell line (CHO-WBL) which supports the notion that the UH associated achromatic lesions in the CHO-K1 line may be a cell line specific phenomenon. Furthermore, careful electron microscopy of the chromosomes revealed chromatin fibers connecting the apparently broken chromosomes. The UH was not observed in the presence of added metabolic activation (S9), and thus the significance of the phenomenon in risk assessment is further reduced. The data presented here provide evidence that sites of UH occur preferentially at locations of C-band positive constitutive heterochromatin in CHO cells; we believe that this is the first report of induced fragile sites in rodent cells in vitro documented in this way. In addition, evidence is presented that U-68,553B lacks the ability to induce breakage in vivo in rodents and lacks the ability to induce chromosome breakage in human peripheral lymphocytes in vitro. Therefore, it is concluded that the positive results with CHO-K1 cells treated with U-68,553B are unlikely to be predictive of a genotoxic hazard. This is a specific example of the importance of careful followup to an in vitro result in risk assessment.

The detection of viable heritable translocations by chromosome banding procedures.

Ethyl methanesulfonate was tested for its ability to induce viable heritable translocations in progeny of male rats given a single IP injection prior to breeding. Reproductively competent Wistar rats were used as the test animals. Males were treated with either 75 or 150 mg/kg EMS or vehicle control. Neonates were used for primary tissue culture; the fibroblasts were harvested for cytogenetic analysis of chromosomes banded by Giemsa banding procedures. Since the cells examined were somatic cells, it was necessary to karyotype only two to three per neonate to ascertain inherited translocations. A reduction in fertility was observed in males treated with EMS. A statistically significant (p less than 0.05) dose-related increase in heritable translocations was observed in the F1 generation of treated animals.