BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].

Objective:To asscentain the 131I activity concentration in 131I treatment workplaces and to explore the method of estimating the internal dose to workers by air sampling and to analyze its influencing factors. Methods:Air sampling method was used to collect aerosols containing radioactivity in 10 randomly selected workplaces in Zhengzhou where 131I therapy was performed. Aactivity concentration of 131I in treatment workplace was measured for gamma emitters by gamma-ray spectrometry. The internal dose due to 131I inhalation was estimated based on measurement result and field investigation result. Results:The activity concentration of 131I in air samples from 19 subpacking rooms ranged from 0.087 to 570 Bq/m 3, with an average of (51.04 ± 128.58) Bq/m 3. Those from 11 wards ranged from 0.162 to 54.6 Bq/m 3, with an average of (7.97 ± 15.89) Bq/m 3. In terms of the work hours recommended by the national standard GBZ 129-2016 Specifications for individual monitoring of occupational internal exposure, the estimated annual effective dose to radiation workers due to the inhalation of 131I ranges from 0.002 to 10 mSv, with an average of (0.61 ± 1.80) mSv, below the dose limit specified in the national standards. Conclusions:The samples with high 131I activity concentration in nuclear medicine workplaces of 10 medical institutions selected in Zhengzhou are mostly distributed in tertiary class hospitals operating large amount of radionuclide with large numbers of thyroid cancer patients adimitted. The result ing internal dose to radiation workers cannot be ignored. Estimating the internal dose based on the measurement result of air samples has a large uncertainty.However, air sampling method can promptly detect radioactive contamination in case of abnormal events or accidents, providing early warning for workers to carry out dose measurement from external exposure and internal exposure assessment.

Objective:To compare the differences in lung function between sanitation workers and the general population undergoing routine physical examinations, and to analyze the risk factors for restricted airflow and severity of the condition in sanitation workers.Methods:This study is a large cross-sectional study called "Shanxin Respiratory Health Screening for Ten Thousand People". A total of 1 036 sanitation workers (sanitation group) and 6 701 individuals from the general population undergoing routine physical examinations (control group) were selected as the original study subjects from June 2021 to April 2022 (before matching). Both groups underwent pre-bronchodilator lung function tests, and the differences in lung function characteristics between the two groups were compared. The sanitation group also completed a questionnaire survey. Multivariate and ordinal multinomial logistic regression analysis were used to analyze the risk factors for airflow limitation and its severity.Results:A total of 1 027 individuals from the sanitation group and 999 individuals from the control group were included in the study. There were no significant differences in age, gender, height, weight, and body mass index (BMI) between the two groups (all P>0.05). The rate of airflow restriction was significantly higher in the sanitation group compared to the control group (22.88% vs 8.81%, P<0.001). In the sanitation group, there was no statistically significant difference in a self-assessment test for chronic obstructive pulmonary disease (CAT) scores between individuals with airflow restriction (235 cases) and those without airflow restriction (792 cases) [(1.50±2.50) vs (1.15±2.03) points, P=0.084]. There were no statistically significant differences in forced vital capacity (FVC) as a percentage of predicted value (FVC%pred) between the two groups. However, the sanitation group had significantly lower %pred for forced expiratory volume in one second (FEV 1%pred), FVC/FEV 1 ratio (FEV 1/FVC%pred), forced expiratory flow at 50% of FVC (FEF 50%%pred), forced expiratory flow at 75% of FVC (FEF 75%%pred), and maximal mid-expiratory flow (MMEF%pred) compared to the control group (all P<0.05). The rates of abnormal FEF 50%%pred, FEF 75%%pred, and MMEF%pred were significantly higher in the sanitation group compared to the control group (17.62% vs 10.31%, 17.04% vs 10.01%, 27.26% vs 18.41%, all P<0.001). Small airway parameters and the rate of airflow restriction were significantly higher in past and current smokers of the sanitation group compared to never smokers (all P<0.05). Multifactorial analysis showed that high BMI ( OR=0.929, 95% CI: 0.885-0.974) was a protective factor for airflow restriction, while high smoking index was a risk factor ( OR=1.020, 95% CI: 1.011-1.030). Ordered multinomial logistic regression analysis showed that high BMI ( OR=0.925, 95% CI: 0.882-0.971) was a protective factor for the severity of airflow restriction, while high smoking index ( OR=1.020, 95% CI: 1.011-1.029) was a risk factor for the severity of airflow restriction. Conclusions:The incidences of airflow limitation and small airway abnormalities in sanitation workers are higher than that in general physical examination population. High smoking index and low BMI are independent risk factors for airflow limitation and its severity.

DECIDE-Diet trial was taken as a case to introduce the methods of blinding and blinding assessment for feeding trials, report the details of blinding, conduct a blinding survey and calculate Jame's BI and Bang's BI. Jame's BI was 0.683 (95% CI: 0.593~0.772). The Bang's BI for the intervention group was 0.340 (95% CI: 0.199~0.481), and for the control group was 0.086 (95% CI: -0.060~0.231). The blinding of the DECIDE)-Diet was generally successful, but the intervention group may infer their group to a certain extent. Feeding trials should report the details of blinding and consider blinding assessment.

Objective:To explore and compare the value of radiomic features based on 18F-fluorodeoxyglucose (FDG) PET and CT in distinguishing epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. Methods:Pretreatment 18F-FDG PET/CT images and EGFR gene status of 114 patients (64 males and 50 females, aged range: 35-84 (average age: 61) years) with primary lung adenocarcinoma between January 2017 and December 2017 were retrospectively collected. The volume of interest was drawn manually slice by slice, then the features were extracted by the LIFEx software. The parameters were screened by least absolute shrinkage and selection operator (LASSO) method for 200 times, and ten-fold cross-validation was used to select the best tuning parameter λ. Three models, namely M PET, M CT, M PET+ CT, were constructed by binary logistic stepwise regression. The receiver operating characteristic (ROC) curve was generated and the corresponding area under the curve (AUC), sensitivity, specificity and accuracy were calculated. The AUCs of three models were compared by Delong test. Results:Totally, 53.51%(61/114) patients were with wild type EGFR and 46.49%(53/114) patients had EGFR mutation. There were 3, 3, 7 parameters selected to form M PET, M CT, M PET+ CT, respectively. The AUCs for M PET, M CT, M PET+ CT were 0.730, 0.752 and 0.866 respectively. When the cut-off values were 0.427, 0.522, 0.378 for M PET, M CT and M PET+ CT, the Youden index were up to the maximum as 0.420, 0.405, 0.630, with sensitivities of 83.0%(44/53), 58.5%(31/53), 92.5%(49/53), specificities of 59.0%(36/61), 82.0%(50/61), 70.5%(43/61) and accuracies of 70.2%(80/114), 71.1%(81/114), 80.7%(92/114), respectively. There was no significant difference between AUC of M PET and M CT ( z=-0.320, P>0.05). The differences of AUCs between M PET+ CT and M PET, M PET+ CT and M CT were statistically significant ( z values: 2.963, 2.523, both P<0.05). Conclusions:PET, CT and PET+ CT radiomic features are all associated with EGFR gene expression in lung adenocarcinoma. M PET+ CT has the highest predictive efficiency.

Objective:To search, evaluate and integrate the best evidence for alleviating intraoperative pain in patients undergoing local anesthesia, so as to provide a basis for formulating intraoperative pain control plan for patients undergoing local anesthesia.Methods:Evidence-based questions were built based on the PICO model. BMJ Best Practice, UpToDate, US Guidelines, National Institute for Health and Clinical Excellence, Scottish Intercollegiate Guidelines Network, Joanna Briggs Institute Evidence-based Health Care Center, Cochrane Library, MedlinePlus, PubMed, CINAHL, Medlive, CNKI and Wanfang Database were searched for guidelines, expert consensus, evidence summary, systematic review and other evidence on alleviating intraoperative pain in patients undergoing local anesthesia. The search time was from the establishment of the database to March 30, 2020. Two researchers with evidence-based nursing knowledge independently evaluated the quality of the literature and the level of evidence.Results:A total of 7 articles were included, including 1 guideline, 1 clinical decision and 5 systematic reviews. The 16 best evidences were summarized from 5 aspects, such as preoperative evaluation, pain recognition, intraoperative pain intervention measures, surgical pain evaluation and health education.Conclusions:This study summarizes the current best evidence for reducing the pain during local anesthesia in patients undergoing local anesthesia and provides evidence-based evidence for the selection of intraoperative pain control programs for local anesthesia in related departments.

Objective:To investigate the effects of microRNA(miR)-133b on epithelial-mesenchymal transition(EM)of human small airway epithelial cells induced by cigarette smoke extracts(CSE)and its regulatory mechanisms.Methods:The miR-expression profiles with microarray in airway epithelial cells of patients with chronic obstructive pulmonary disease were searched in the Gene Expression Omnibus(GEO)database, and the differentially expressed miRs were searched and verified by a real-time fluorescence quantitative method(qRT-PCR). Human small airway epithelial cells(HSAEpiC)were divided into the control group, the CSE group, the CSE+ miR-133b inhibitor transfection group(inhibitor group)and the CSE+ miR-133b inhibitor negative control transfection group(inhibitor control group)according to different intervention methods.Levels of miR-133b and mRNA levels of transforming growth factor(TGF)-β1, Smad2, E-cadherin and vimentin were detected by RT-PCR; Protein levels of E-cadherin and vimentin were detected by enzyme-linked immunosorbent assays(ELISA)and Western blotting.Results:Nine differentially expressed miRs were found in GSE53519, with miR-133b showing the most significant differential in thee HSAEpiC cell model after verification.CSE induced morphological changes in HSAEpiC cells, and miR-133b inhibitors could partially reverse the morphological changes in cell mode.mRNA and protein expressions of E-cadherin were decreased and expression of Vimentin mRNA and protein were increared in CSE induced HSAEpiC cells( F=9.09、12.35、7.57、101.87, P=0.015、0.007、0.023、0.000); miR-133b inhibitors partally reversed the mRNA and protein expressions of E-cadherin and Vimentin( F=40.59、27.74、15.87、20.42, P=0.000、0.001、0.004、0.002). CSE induced incresed expression of TGF-β1 mRNA and Smad mRNA in HSAEpiC cells, and miR-133b inhibitors partially reversed the changes in TGF-β1 mRNA and Smad mRNA( F=17.25、64.15, P=0.003、0.000). Conclusions:miR-133b may regulate CSE-related HSAEpiC cell EMT through the TGF-β1/Smad pathway.

Objective To study the trends in surgical treatment and the outcomes of critical acute pancreatitis (CAP).Methods The clinical data of 76 patients with CAP who were treated in the Department of Biliopancreatic Surgery of the Xiangya Hospital,Central South University from January 2010 to December 2017 were retrospectively reviewed.Data which included demographics,micro-organisms,surgical interventions and mortality were compared between the time periods of 2010 to 2013 and 2014 to 2017.Results Before 2014,19 patients with CAP were treated in the Department of Biliopancreatic Surgery of the Xiangya Hospital,Central South University.The percentage of multidrug resistant organisms (MDRO) in pancreatic drainage was 5.3％ (1/19).In the latter 4 years,57 patients with CAP were treated.The percentage of MDRO was 50.9％ (29/57),which was significandy higher than the initial 4 years (P＜0.001).For surgical treatment,the proportion of minimally invasive surgery in the latter 4 years was significantly higher than that in the initial 4 years.The percentage of percutaneous catheter drainage (PCD) increased from 63.2％ in the initial 4 years to 86.0％ in the latter 4 years.The proportion of minimal access retroperitoneal pancreatic necrosectomy (MARPN) increased from zero in the initial 4 years to 59.6％,while the proportion of open pancreatic necrosectomy (OPN) decreased from 68.4％ in the initial 4 years to 24.6％.The mortality rate of patients with CAP dropped from 52.6％ (10/19) in the initial 4 years to 24.6％ (14/57) in the latter four years.Conclusions In the center which specializes in treating pancreatitis,although the problem of bacterial resistance had become increasingly prominent,the mortality rate of CAP had shown a significant downward trend due to the development of various minimally invasive techniques.