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Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus... (Review)
Review
Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in infections.
Topics: Humans; Interferons; Aspergillus; Aspergillosis; Pulmonary Aspergillosis
PubMed: 38955753
DOI: 10.3760/cma.j.cn112147-20240226-00106 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and...
To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.
Topics: Humans; Male; Female; Tuberculosis, Multidrug-Resistant; Adult; Prospective Studies; Rifampin; Middle Aged; Oxazoles; Antitubercular Agents; Tuberculosis, Pulmonary; Nitroimidazoles; Aged; China; Young Adult; Drug-Related Side Effects and Adverse Reactions
PubMed: 38955749
DOI: 10.3760/cma.j.cn112147-20240229-00117 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jul 2024Patients with chronic obstructive pulmonary disease (COPD) may present with various forms of pulmonary aspergillosis, including invasive pulmonary aspergillosis (IPA),... (Review)
Review
Patients with chronic obstructive pulmonary disease (COPD) may present with various forms of pulmonary aspergillosis, including invasive pulmonary aspergillosis (IPA), chronic cavitary pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis. Accurate diagnosis and disease evaluation are essential for tailoring individualized treatment strategies. Key aspects include: (1) Comprehensive assessment of IPA risk factors, with enhanced monitoring for critically ill patients; (2) Understanding the clinical manifestations and radiological features of different forms of pulmonary aspergillosis and emphasizing the importance of bronchoscopic examination; (3) Obtaining microbiological evidence whenever possible; (4) Differentiating colonization from infection to avoid overdiagnosis; (5) Vigilance for co-existing sensitization to . During treatment and long-term disease management, the use of inhaled or systemic corticosteroids and antifungal agents should be dynamically adjusted according to the patient's condition.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Aspergillosis; Risk Factors; Invasive Pulmonary Aspergillosis; Antifungal Agents; Bronchoscopy
PubMed: 38955745
DOI: 10.3760/cma.j.cn112147-20240514-00256 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead... (Review)
Review
Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".
Topics: Humans; One Health; Public Health; Anti-Bacterial Agents; Drug Resistance, Bacterial
PubMed: 38955741
DOI: 10.3760/cma.j.cn112150-20231127-00379 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of e from respiratory specimen sources. A...
To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of e from respiratory specimen sources. A total of 35 strains of meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly B, with a carrying rate of 74.2%; tetracycline resistance genes were mainly M, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants A and C were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, , 1, , , and r_0594, and seven virulence factors, E, A, B, l, and A. Overall, isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by from respiratory tract speciments of elderly patients.
Topics: Streptococcus agalactiae; Humans; Aged; Anti-Bacterial Agents; Middle Aged; Microbial Sensitivity Tests; Aged, 80 and over; Adult; Child; Adolescent; Child, Preschool; Infant; Young Adult; Infant, Newborn; Drug Resistance, Bacterial; Streptococcal Infections
PubMed: 38955738
DOI: 10.3760/cma.j.cn112150-20231214-00446 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes...
To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, =490), complication group 1 (1 microvascular complications, =217), and complication group 2 (2 or more microvascular complications, =129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (=537.470, 791.690, 136.340, <0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) μg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) μg/ml] and complication group 2 [30.42 (12.53, 47.26) μg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (=210.020, <0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (=-0.431, -0.372, -0.546, <0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (=2.261, 95%: 1.564-3.269), increased HbA1c (=2.040, 95%: 1.456-2.858), and increased HOMA-IR (=2.158, 95%: 1.484-3.137) and decreased 1, 5-AG (=2.512, 95%: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%: 0.692-0.767). Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Cross-Sectional Studies; Retrospective Studies; Deoxyglucose; Blood Glucose; Male; Female; Insulin; Middle Aged; Diabetic Angiopathies
PubMed: 38955736
DOI: 10.3760/cma.j.cn112150-20240219-00129 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jul 2024
Topics: Humans; Anthraquinones; Vascular Calcification; Atherosclerosis; Silver Nitrate; Renal Insufficiency, Chronic; Staining and Labeling; Aortic Aneurysm; Calcium; Silver Staining
PubMed: 38955708
DOI: 10.3760/cma.j.cn112151-20231206-00394 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jul 2024
Review
Topics: Humans; Pneumonia, Mycoplasma; China; Mycoplasma pneumoniae; Child; Macrolides; Anti-Bacterial Agents; Child, Preschool; Drug Resistance, Bacterial
PubMed: 38955692
DOI: 10.3760/cma.j.cn112140-20240407-00247 -
Journal For Immunotherapy of Cancer Jul 2024Immune checkpoint blockade targeting the adaptive immune system has revolutionized the treatment of cancer. Despite impressive clinical benefits observed, patient...
BACKGROUND
Immune checkpoint blockade targeting the adaptive immune system has revolutionized the treatment of cancer. Despite impressive clinical benefits observed, patient subgroups remain non-responsive underscoring the necessity for combinational therapies harnessing additional immune cells. Natural killer (NK) cells are emerging tools for cancer therapy. However, only subpopulations of NK cells that are differentially controlled by inhibitory receptors exert reactivity against particular cancer types. How to leverage the complete anti-tumor potential of all NK cell subsets without favoring the emergence of NK cell-resistant tumor cells remains unresolved.
METHODS
We performed a genome-wide CRISPR/Cas9 knockout resistance screen in melanoma cells in co-cultures with human primary NK cells. We comprehensively evaluated factors regulating tumor resistance and susceptibility by focusing on NK cell subsets in an allogenic setting. Moreover, we tested therapeutic blocking antibodies currently used in clinical trials.
RESULTS
Melanoma cells deficient in antigen-presenting or the IFNγ-signaling pathways were depleted in remaining NK cell-co-cultured melanoma cells and displayed enhanced sensitivity to NK cells. Treatment with IFNγ induced potent resistance of melanoma cells to resting, IL-2-cultured and ADCC-activated NK cells that depended on required for the expression of both classical and non-classical MHC-I. IFNγ-induced expression of HLA-E mediated the resistance of melanoma cells to the NKG2A KIR and partially to the NKG2A KIR NK cell subset. The expression of classical MHC-I by itself was sufficient for the inhibition of the NKG2A KIR, but not the NKG2A KIR NK cell subset. Treatment of NK cells with monalizumab, an NKG2A blocking mAb, enhanced the reactivity of a corresponding subset of NK cells. The combination of monalizumab with lirilumab, blocking KIR2 receptors, together with DX9, blocking KIR3DL1, was required to restore cytotoxicity of all NK cell subsets against IFNγ-induced resistant tumor cells in melanoma and tumors of different origins.
CONCLUSION
Our data reveal that in the context of NK cells, IFNγ induces the resistance of tumor cells by the upregulation of classical and non-classical MHC-I. Moreover, we reveal insights into NK cell subset reactivity and propose a therapeutic strategy involving combinational monalizumab/lirilumab/DX9 treatment to fully restore the antitumor response across NK cell subsets.
Topics: Humans; Killer Cells, Natural; Interferon-gamma; Melanoma; Cell Line, Tumor; Coculture Techniques
PubMed: 38955423
DOI: 10.1136/jitc-2024-009410 -
CMAJ : Canadian Medical Association... Jul 2024
Topics: Humans; HIV Infections; Post-Exposure Prophylaxis; Anti-HIV Agents; Canada
PubMed: 38955414
DOI: 10.1503/cmaj.240064