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Objective:To explore the influence of airway mucus plugs on patients with bronchial asthma and its management.Methods:In this cross-sectional study, from January 2020 to June 2022, 100 patients who were diagnosed with asthma and underwent chest CT examination in the Outpatient Department of Peking University Third Hospital were included. The chest CT results and medical history, pulmonary function, fractional exhaled nitric oxide (FeNO), blood routine, total allergen IgE, Aspergillus fumigatus M3 allergen-specific IgE antibody test results were collected. According to the results of chest CT, the asthma patients were divided into group with mucus plugs and those without mucus plugs. Distribution of airway mucus plugs and the mucus plug scores based on lung segments were calculated. The relationships of mucus plugs with medical history, pulmonary function [These included before and after the bronchodilation test, forced vital capacity percent of predicted value (FVC%pred), forced expiratory volume in one second percent of predicted value (FEV 1%pred), FEV 1/FVC, peak expiratory flow percent of predicted value (PEF%pred), maximal mid-expiratory flow percent of predicted value (MMEF%pred), maximal expiratory flow at 25%, 50%, 75% of vital capacity remaining percent of predicted value (MEF 25%pred, MEF 50%pred, MEF 75%pred)], FeNO, and peripheral blood eosinophil (Eos) counts were analyzed. The logistic regression model was used to analyze whether airway mucus plug was a risk factor for asthma exacerbation, and the corresponding intervention strategies were explored. Results:Among the 100 patients with asthma, 24 cases were in the mucus plug group and 76 cases were in the non-mucus plug group. The distribution of mucus plug was more common in the lower lungs (30.53% and 9.16% in the lower and upper lobe of left lung, respectively; 29.01%, 14.50% and 16.80% in the lower, middle and upper lobe of right lung, respectively). The average score of mucus plug was (4.42±3.12) points. The body mass index (BMI), the number of visits to a doctor due to asthma exacerbations, FeNO, peripheral blood Eos counts in the mucus plug group were higher than those in the non-mucus plug group [(24.95±4.34) vs (23.22±2.91) kg/m 2, 0(0, 1) vs 0(0, 0), 97(37, 169) vs 31(18, 59) ppb (1 ppb=1×10 -9), 0.41(0.15, 0.70) vs 0.18(0.09, 0.37)×10 9/L](all P<0.05), and FVC%pred, FEV 1%pred, FEV 1/FVC, PEF%pred, MEF 50%pred, MEF 25%pred, MMEF%pred, MEF 75%pred were lower than those in the non-mucus plug group [(87.49±19.32)% vs (97.34±14.24)%, (76.49±19.58)% vs (91.07±18.33)%, (72.44±10.91)% vs (79.48±8.13)%, (82.36±24.46)% vs (93.83±18.27)%, (53.03±24.81)% vs (75.75±27.15)%, (46.47±22.92)% vs (64.09±25.90)%, (50.28±23.73)% vs (74.53±26.80)%, (71.30±27.55)% vs (89.92±26.82)%] (all P<0.05). In the group with mucus plug, the airway mucus plug score was positively correlated with the patient′s body weight and the number of peripheral blood Eos counts at enrollment ( r=0.413, 0.478; all P<0.05), and negatively correlated with FVC%pred and FEV 1%pred ( r=-0.576, -0.465; all P<0.05). Logistic regression analysis showed that airway mucus plug score was a risk factor for acute asthma attack ( OR=1.269, 95% CI: 1.031-1.562; P=0.024). Conclusions:Asthma patients have a high incidence of airway mucus plug, which is related to the level of Eos inflammation and body size. Airway mucus plugs can promote airflow obstruction and acute exacerbation of asthma. In clinical practice, appropriate asthma management policies can be formulated for airway mucus plugs to delay the progression of asthma and reduce the number of acute attacks.
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Objective:To study the correlation between peripheral blood eosinophils levels and clinical characteristics of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A retrospective study was conducted in 79 AECOPD patients admitted to the Department of Respiratory and Critical Care Medicine of Peking University Third Hospital from January 2015 to December 2016. Peripheral blood EOS level 100/μl, 300/μl, 2%, 3%, and sputum EOS level 3% were the cut-off values. Patients were divided into EOS≥100/μl group ( n=33), EOS<100/μl group ( n=46); EOS≥300/μl group ( n=10), EOS<300/μl group ( n=69); EOS%≥2% group ( n=27), EOS<2% group ( n=52); blood EOS≥3% group ( n=16), blood EOS<3% group ( n=63); sputum EOS≥3% group ( n=7), sputum EOS<3% group ( n=15) respectively. The study analyzed the differences of clinical features between each two groups of patients; According to the blood EOS level in the acute phase and the recovery phase, ≥100/μl was high and<100/μl was low, they were divided into high EOS in both acute and recovery phase group ( n=21), high EOS in the acute phase and low EOS in the recovery phase group ( n=4), low EOS in the acute phase and high EOS in the recovery phase group ( n=20) and low EOS in both acute and recovery phase group ( n=12). The differences of clinical characteristics in each group were analyzed. Results:The median duration of COPD, proportion of patients with forced expiratory volume in the first second (FEV 1) percentage of predicted value (FEV 1% predicted value)<50%, proportion of complicated with respiratory failure, median level of procalcitonin, proportion of systemic glucocorticoid therapy and median length of stay in the EOS≥100/μl group were all significantly lower than EOS<100/μl group (5 vs 13 years, 48.0% vs 81.8%, 21.9% vs 50.0%, 0.04 vs 0.09 μg/L, 21.2% vs 56.5%, 11 vs 14 d, all P<0.05). The proportion of re-acute exacerbation in the EOS≥300/μl group was significantly higher than EOS<300/μl group (60.0% vs 23.2%), while the median fibrinogen level and median procalcitonin level were significantly lower than EOS<300/μl group (3.38 vs 3.85 g/L, 0.03 vs 0.07 μg/L, all P<0.05). The median duration of COPD, proportion of FEV 1% predicted value<50%, proportion of complicated with respiratory failure, the modified British Medical Research Council′s dyspnea scale (mMRC) score, median fibrinogen level, median C-reactive protein level, median procalcitonin level, proportion of systemic glucocorticoid therapy, proportion of non-invasive ventilation during hospitalization and median length of stay in the EOS≥2% group were all significantly lower than EOS<2% group [5 vs 13 years, 40.9% vs 83.3%, 12.0% vs 51.0%, 3 (2, 3) vs 3 (3, 4) points, 3.37 vs 3.97 g/L, 3.6 vs 16.8 mg/L, 0.04 vs 0.09 μg/L, 14.8% vs 55.8%, 0 vs 19.2%, 9 vs 14 d] (all P<0.05). The median duration of COPD, proportion of complicated with respiratory failure, median level of C-reactive protein and proportion of systemic glucocorticoid therapy in the blood EOS≥3% group were significantly lower than blood EOS<3% group (5 vs 10 years, 6.7% vs 45.8%, 4.4 vs 12.9 mg/L, 12.5% vs 49.2%) (all P<0.05). The median duration of COPD and median length of stay in the sputum EOS≥3% group were significantly shorter than sputum EOS<3% group (2 vs 15 years, 10 vs 21 d), while the median blood EOS count and median blood EOS ratio were significantly higher than sputum EOS<3% group (0.20 vs 0.01×10 9/L, 2.4% vs 0.1%) (all P<0.05). The proportion of complicated with respiratory failure and received systemic glucocorticoid therapy in the high EOS in both acute and recovery phase group were significantly lower than the low EOS in the acute phase and high EOS in the recovery phase group (14.3% vs 75.0%, 14.3% vs 55.0%) (all P<0.05). The proportion of FEV 1% predicted value <50% in the high EOS in the acute phase and low EOS in the recovery phase group was significantly lower than the low EOS in the acute phase and high EOS in the recovery phase group (0 vs 82.4%) ( P<0.05). The median FEV1% predicted value level in the high EOS in the acute phase and low EOS in the recovery phase group was significantly higher than the low EOS in both acute and recovery phase group (59.5% vs 36.0%) ( P<0.05). Conclusions:High EOS AECOPD patients have a shorter duration of disease and fewer days of hospitalization. The proportion of patients complicated with respiratory failure is lower. It is easier to distinguish the differences in clinical characteristics of AECOPD patients with a blood EOS count of 100/μl as a cut-off value. EOS levels in the acute phase and the recovery phase are helpful to distinguish the clinical characteristics of AECOPD patients.
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Tuberculosis is one of the seriously public problems. The increasing drug-resistant tuberculosis is the key problem for controlling tuberculosis. Rapid and accurate diagnosis is important for further treatment. In this study‚ a next-generation sequencing method based on amplicon sequencing was constructed to screen the mutations in 17 drug-resistant genes of five first-line anti-tuberculosis drugs. A total of 65 mutations were identified in 26 clinic drug-resistant tuberculosis strains‚ including 33 hotspot mutations‚ 9 rare mutations‚ and 23 novel mutations. The pathogenesis‚ conservation‚ and partial structures caused by 18 novel missense mutations were predicted. The results showed that 14 novel mutations showed high conservation in nine species. All these 14 mutations could change the partial structure of protein. According to the detection and analysis results of this study‚ it is speculated that these newly discovered mutations may be potential drug-resistant mutations. It is a rapid‚ accurate and comprehensive method for the detection of drug-resistant mutations in first-line drug-resistant Mycobacterium tuberculosis‚ which could identify hotspot and rare mutations together with novel mutations. The detection method may be used for clinical diagnosis and basic research.
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Objective @#To investigate the effects of intra-articular injection of alendronate on the mandibular condyle in ovariectomized rats.@*Methods @#Sixty female rats were randomly divided into five groups: ovariectomy with vehicle treatment alone, early alendronate treatment at ovariectomy, late alendronate treatment at 4 weeks after ovariectomy, shamoperation with vehicle treatment, and the normal control rats. The changes in subchondral bone were evaluated by micro-computed tomography (Micro-CT), tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction (RT-PCR). @*Results @# Compared with late alendronate treatment, early alendronate treatment improved microstructural properties of the subchondral bone, with higher bone volume ratio (46.4 + 2.5 vs 37.5 + 2.1; P= 0.038), increased trabecular thickness (47.3 + 1.7 vs 34.6 + 1.4; P = 0.029), elevated trabecular number (8.5 + 0.6 vs 6.2 + 0.3; P = 0.041) and lower trabecular separation (30.2 + 1.6 vs 37.7 + 2.6; P = 0.034). Fewer TRAP-positive cells (4.2 + 0.2 vs 6.8 + 0.4; P = 0.019) and a higher OPG/RANKL ratio (0.38 + 0.01 vs 0.25 + 0.03; P = 0.043) in the subchondral bone were observed in the animals with early treatment group compared to late treatment or ovariectomy/vehicle treatment group. @*Conclusion @#Our results suggest the therapeutic potential of intra-articular alendronate injection in the treatment of osteoporosis-associated temporomandibular disorders.
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Objective@# To investigate the expression of Notch signaling molecules in temporomandibular joint arthritis (TMJOA), and to explore the role and mechanism of Notch signaling pathway in the development and progression of TMJOA. @*Methods @#72 Kunming mice were randomly divided into experimental group, sham-surgery group and normal group. In experimental group, discs on the right TMJ were subjected to total discectomy, sham-operation group underwent the same procedure without disc removal, while normal group serve as blank control. All the left temporomandibular joint discs were not treated. 8 mice in each group were sacrificed respectively at 1 week, 2 week, 4 week after surgery. Histological examinations were performed to assess success of TMJOA model, according to the pathological standard of osteoarthritis diagnosis. Immunochemistry techniques were performed in the successful TMJOA cartilages to evaluate the expression levels of Notch1 (NICD1), Jagged1, Hes1 and Hes5. The scores were evaluated by semi-quantitative method. @*Results @#Notch1 (NICD1), Jagged1 and Hes5 were activated in the experimental group with the expression levels increased dramatically over time. While Hes1 expression was suppressed at the beginning of osteoarthritis but was up-regulated afterwards.@*Conclusion @# Notch pathway-related molecular expression changed greatly in TMJOA model, indicating that the pathway in the occurrence and development of TMJOA plays an important role.
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Objective To better understand the mechanisms of cone opsin transport , we set to generate a trans-genic zebrafish line with red fluorescence proteins expressing in the cone photoreceptors .Methods We used sws1 promot-er to drive the expression of a chimerical protein , in which the last 44 amino acids of rhodopsin of Xenopus laevis were fused to the C-terminus of tdTomato to restrict its localization to the outer segment of photoreceptors .Results We successfully i-solated such a transgenic zebrafish line and confirmed the localization of tdTomato by immunostaining analysis .Conclu-sions This transgenic zebrafish line will help us to better understand the transport mechanisms of cone opsins , especially the transport in live photoreceptors .
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Prostate cancer is one of the most common type of cancer among men after middle age. Androgen withdrawal can delay its progression in the initial stage, but it finally becomes independent of androgens in almost all the cases. The combination of docetaxel with prednisone is currently a standard first-line treatment for patients with hormone-refractory prostate cancer (HRPC), but hitherto there is no established second-line therapy. In view of the molecular pathogenesis of HRPC, this article presents an overview on several promising drugs that target specific pathways, involving angiogenesis, cell signaling, apoptosis and proliferation, and immune modulation, either as single agents or in combination with cytotoxic chemotherapy.
Subject(s)
Humans , Male , Drug Resistance, Neoplasm , Hormones , Pharmacology , Prostatic Neoplasms , Drug TherapyABSTRACT
In China, the incidence of prostate cancer has been increasing in recent years. Hormonal therapy has been the mainstay of the therapeutic options for metastatic diseases for many years. But many metastatic tumors progress at a median of two to five years and become hormonal refractory prostate cancer (HRPC). This article summarizes in the advances of diagnostic criteria, molecular biological features, prediction markers, new therapeutic agents and further researches to be undertaken concerning HRPC.
Subject(s)
Aged , Humans , Male , Androgen Antagonists , Pharmacology , Biomarkers, Tumor , Drug Resistance, Neoplasm , Prostatic Neoplasms , Diagnosis , Drug Therapy , PathologyABSTRACT
@#ObjectiveTo explore the effect of community education and service of mental health on improvement of people's diathesis.Methods483 subjects from 6 social strata were investigated with the questionnaire to find out the community resident's idea on mental health and need for psychological service.ResultsThere were significant differences in the concepts of criteria of mental health among people in different social strata and ages (P<0.001),and requirements for community education and service of mental health varied from one to another. Forms and contents of community education and service were multiplicate.ConclusionThe community education and service of mental health should be developed widely for improving people's diathesis.