Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

Objective:To explore the understanding on health-related quality of life(HRQoL)among the Chinese populations and to develop a HRQoL conceptual framework that can be used to guide the development of Chinese HRQoL instruments.Methods:Respondents of Chinese general population and patients populations were recruited from 31 provinces in China.One-to-one semi-structured qualitative interviews were conducted to collect the views and perceptions on HRQoL.Based on the grounded theory,multi-level coding of qualitative interviews was carried out,and the framework method was used to sort out and summarize the coding to develop the HRQoL conceptual framework in China.Results:A total of 68 respondents were included in the study.The study extracted 1 558 open coding from the qualitative interview,which were analyzed and sorted into 180 axial coding and 31 selective coding(dimensions).The HRQoL conceptual framework for the Chinese population with 6 themes was finally summarized.Conclusions:The HRQoL conceptual framework based on the health concepts and preferences of the Chinese population contains 6 themes,refers to symptoms,physical function,emotion,cognition,activities and social function.In particular,the items of appetite,sleep and fatigue identifies may reflect Chinese cultural specific perceptions on important aspects of HRQoL.

Objective To explore the association of Toll-like receptor 7, CTLA-4 gene polymorphisms and severe asthma. Methods From February 2018 to March 2020, 175 asthma patients admitted to the respiratory department of our hospital were selected as the research subjects (109 cases of mild disease and 66 cases of severe disease), and 248 cases of healthy people who were included in the outpatient physical examination of our hospital during the same period were selected as the normal control group. Toll-like receptor 7 and CTLA-4 gene polymorphisms in the above groups were determined, and the relationship between Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma was evaluated by calculating the odds ratio (OR) and 95% confidence interval(CI). The relationship between the genotypes of Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma were evaluated by logistic regression analysis. Results The proportion of TLR7 rs3853839 CC genotype, CTLA-4 rs231725 AA genotype, TLR7 rs3853839 C allele frequency and CTLA-4 rs231725 A allele frequency in severe asthma group and mild asthma group were higher than those in normal control group(P<0.05). The proportion of TLR7 rs3853839 CC genotype, the proportion of CTLA-4 rs231725 AA genotype, the frequency of TLR7 rs3853839 C allele, and the frequency of CTLA-4 rs231725 A allele in the severe asthma group were higher than those in the mild asthma group(P<0.05). TLR7 rs3853839 CC genotype (OR=10.32, 95%CI=5.59-23.89), CTLA-4 rs231725 AA genotype (OR=13.21, 95%CI=3.58-20.25), TLR7 rs3853839 C allele frequency (OR=11.32, 95% CI=4.25-21.14) and CTLA-4 rs231725 A allele frequency (OR=13.24, 95% CI=6.59-20.21) could increase the susceptibility to severe asthma(P<0.05). TLR7 rs3853839CC genotype, TLR7 rs3853839C allele frequency, CTLA-4 rs231725AA genotype and CTLA-4 rs231725A allele frequency were risk factors for severe asthma(P<0.05). Conclusion TLR7 rs3853839 CC genotype, TLR7 rs3853839 C allele frequency, CTLA-4 rs231725 AA genotype and CTLA-4 rs231725 A allele frequency are associated with the occurrence of severe asthma.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.
Humans ; Rifampin/therapeutic use* ; Antibiotics, Antitubercular/therapeutic use* ; Mycobacterium tuberculosis ; Ethambutol/pharmacology* ; Isoniazid/pharmacology* ; Paraffin Embedding ; Retrospective Studies ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Sensitivity and Specificity ; Tuberculosis, Multidrug-Resistant/drug therapy*

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Objective To report 5 cases of amyloid arthropathy with joint flexion contracture as the first manifestation,and perform a literature review to improve the understanding of the disease.Methods Retrospective analysis of the clinical manifestations,laboratory and imaging results clinical data of patients with immunoglobulin light chain(AL)amyloidosis related amyloid arthropathy with joints flexion contracture as the first manifestation at the Department of Rheumatology and Immunology,the First Medical Center of People's Liberation Army General Hospital from January 2012 to February 2022.Meanwhile searching the database(CNKI,Wanfang Data,PubMed),excluding myeloma-associated amyloid arthropathy,and analyzing the literature results comprehensively.Results There were a total of 5 patients with amyloid arthropathy with joint flexion contracture as the initial manifestation in this center,including 4 males and 1 female.By February 2022(searching CNKI,Wanfang Data and PubMed),two eligible patients were selected,all males.A total of 7 patients were included with male-to-female ratio of 6:1.The median age was 30-year-old(range from 19 to 73).Spine and limb joints were involved,especially finger joints(7 cases,100%).Soft tissue was involved in 5 patients(71.4%),carpal tunnel syndrome in 4 patients(57.1%),giant tongue in 3 patients(42.9%),shoulder pad sign in 2 patients(28.6%),muscle swelling in 2 patients(28.6%).Five patients were misdiagnosed as rheumatoid arthritis(RA)and 1 patient was misdiagnosed as spondyloarthritis(SpA).The median time of delayed diagnosis was 24 months(2-204 months).The laboratory results showed that 3 patients(42.9%)were positive for immunoelectrophoresis,all of which were λ light chain.Only 1 patient was positive for HLA-B27,while the other patients were negative for autoantibodies and rheumatoid factors.Only 1 patient had elevated C reactive protein(CRP)and erythrocyte sedimentation rate(ESR).Ultrasound examination of the lesion site of 5 patients(71.4%)showed hypoechoic area around the joint,thickening of ligaments or periarticular tenosynovitis.Five patients(71.4%)underwent X-ray examination,of which 4 patients had no bone destruction,1 patient had soft tissue swelling with bone erosion and subchondral cyst.MRI was performed in 5 patients(71.4%),in which low signal on T1 weighted image,medium signal on T2 weighted image and edema signal on peripheral tendon sheath were seen in 1 patient.One patient(14.3%)underwent emission computed tomography(ECT)without abnormal uptake.Conclusion Joint flexion contracture may be the first sign of amyloid arthropathy.Vigilance for amyloid arthropathy is warranted when there is associated soft tissue involvement,negative autoantibodies,and imaging showing no joint destruction but surrounding soft tissue abnormalities.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*