Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Clinical feasibility of post-contrast accelerated 3D T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) with iterative denoising for intracranial enhancing lesions: a retrospective study.

BACKGROUND: Post-contrast T1-Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) is the preferred 3D T1 spin-echo sequence for evaluating brain metastases, regardless of the prolonged scan time. PURPOSE: To evaluate the application of accelerated post-contrast T1-SPACE with iterative denoising (ID) for intracranial enhancing lesions in oncologic patients. MATERIAL AND METHODS: For evaluation of intracranial lesions, 108 patients underwent standard and accelerated T1-SPACE during the same imaging session. Two neuroradiologists evaluated the overall image quality, artifacts, degree of enhancement, mean contrast-to-noise ratiolesion/parenchyma, and number of enhancing lesions for standard and accelerated T1-SPACE without ID. RESULTS: Although there was a significant difference in the overall image quality and mean contrast-to-noise ratiolesion/parenchyma between standard and accelerated T1-SPACE without ID and accelerated SPACE with and without ID, there was no significant difference between standard and accelerated T1-SPACE with ID. Accelerated T1-SPACE showed more artifacts than standard T1-SPACE; however, accelerated T1-SPACE with ID showed significantly fewer artifacts than accelerated T1-SPACE without ID. Accelerated T1-SPACE without ID showed a significantly lower number of enhancing lesions than standard- and accelerated T1-SPACE with ID; however, there was no significant difference between standard and accelerated T1-SPACE with ID, regardless of lesion size. CONCLUSION: Although accelerated T1-SPACE markedly decreased the scan time, it showed lower overall image quality and lesion detectability than the standard T1-SPACE. Application of ID to accelerated T1-SPACE resulted in comparable overall image quality and detection of enhancing lesions in brain parenchyma as standard T1-SPACE. Accelerated T1-SPACE with ID may be a promising replacement for standard T1-SPACE.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

cis-Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.

cis-Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis-regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome-wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single-nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis-regulatory variations likely control kernel size by fine-tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis-regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis-regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement.

Risk estimation for idiopathic normal-pressure hydrocephalus: development and validation of a brain morphometry-based nomogram.

OBJECTIVES: To develop and validate a nomogram based on MRI features for predicting iNPH. METHODS: Patients aged ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning-based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated. RESULTS: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample. CONCLUSION: A brain morphometry-based nomogram including high-convexity tightness, callosal angle < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH. KEY POINTS: • The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. • The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Dietary quality and the gut microbiome in early-stage Parkinson's disease patients.

BACKGROUND: The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition. METHODS: This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences. RESULTS: Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls. CONCLUSIONS: Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed.

A collaborative study to establish the second national standard for hepatitis B immunoglobulin in Korea.

This study aimed to establish a second national standard for hepatitis B immunoglobulin (HBIG) that can be used for potency assays of hepatitis B and normal immunoglobulin. The candidate material was manufactured using a process approved as Good Manufacturing Practice. The freeze-dried candidate preparation was tested for physicochemical and biological properties, including pH, residual moisture, molecular size distribution, and potency. A collaborative study was performed involving four laboratories, including the National Institute of Food and Drug Safety Evaluation, as an official national control laboratory in Korea and manufacturers. The potency was calibrated against the second international standard for HBIG using two enzyme immunoassays: enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay. Results from 240 assays were obtained from four laboratories, and combined potency estimates were obtained by calculating the geometric means. Intra- and inter-laboratory variability showed acceptable geometric coefficients of variation of 1.3-6.0 and 3.2-3.6%, respectively. The candidate preparation showed satisfactory stability in accelerated thermal degradation and real-time stability tests. Based on these results, the potency value of 105 IU/vial was assigned (95% confidence intervals: 100.0-109.2 IU/vial), and it was deemed suitable to serve as the Korean national standard for HBIG.

Risk of Rapid Lung Function Decline in Young Adults With Chronic Obstructive Pulmonary Disease: A Community-Based Prospective Cohort Study.

It is unclear whether young adults with chronic obstructive pulmonary disease (COPD) are at an increased risk of rapid lung function decline. A total of 2,934 Korean adults aged 40-49 years who had consecutive lung function measurements were included. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity < lower limit of normal. The risk of rapid decline in FEV1, defined as ≥ 60 mL/year, was assessed using multivariable logistic regression analysis. In the multivariable model, a significantly higher risk of rapid decline in FEV1 was observed for the COPD group compared with the non-COPD group (adjusted odds ratio, 1.89; 95% confidence interval, 1.18-2.95), which was especially significant in subjects with FEV1 less than the median value (< 110%pred) (Pinteraction = 0.017) and inactive physical activity (Pinteraction = 0.039). In conclusion, the risk of rapid FEV1 decline was higher in young adults with COPD than in those without COPD, especially in those with FEV1 less than the median value and inactive physical activity.

Design of Low-Noise CMOS Image Sensor Using a Hybrid-Correlated Multiple Sampling Technique.

We present a 320 × 240 CMOS image sensor (CIS) using the proposed hybrid-correlated multiple sampling (HMS) technique with an adaptive dual-gain analog-to-digital converter (ADC). The proposed HMS improves the noise characteristics under low illumination by adjusting the ADC gain according to the incident light on the pixels. Depending on whether it is less than or greater than 1/4 of the full output voltage range from pixels, either correlated multiple sampling or conventional-correlated double sampling (CDS) is used with different slopes of the ramping signals. The proposed CIS achieves 11-bit resolution of the ADC using an up-down counter that controls the LSB depending on the ramping signals used. The sensor was fabricated using a 0.11 µm CIS process, and the total chip area was 2.55 mm × 4.3 mm. Compared to the conventional CDS, the measurement results showed that the maximum dark random noise was reduced by 26.7% with the proposed HMS, and the maximum figure of merit was improved by 49.1%. The total power consumption was 5.1 mW at 19 frames per second with analog, pixel, and digital supply voltages of 3.3 V, 3.3 V, and 1.5 V, respectively.

Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

Effect of Home-Based Self-Management Intervention for Community-Dwelling Patients with Early Parkinson's Disease: A Feasibility Study.

PURPOSE: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). DESIGN: A randomized-controlled design. METHODS: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. FINDINGS: Physical activity and non-motor symptoms improved more in the intervention group than in the control group. CONCLUSION: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. CLINICAL EVIDENCE: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.

Association between non-cystic fibrosis bronchiectasis and the risk of incident dementia: A nationwide cohort study.

BACKGROUND: Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. OBJECTIVES: To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. METHODS: A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer's disease and vascular dementia. RESULTS: During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p < .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04-1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer's disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01-1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90-1.21). CONCLUSION: Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer's disease.

Comparison of n-butyl-2-cyanoacrylate and polyvinyl alcohol particles for bronchial artery embolisation in primary lung cancer: a retrospective cohort study.

BACKGROUND: Bronchial artery embolisation (BAE) is an effective treatment option to control haemoptysis in primary lung cancer. However, no studies have investigated optimal embolisation material for BAE in lung cancer patients. Thus, this study aimed to compare the safety and efficacy of BAE performed using n-butyl-2-cyanoacrylate (NBCA) and polyvinyl alcohol (PVA) particles in primary lung cancer patients to determine which embolic material is better for patients with haemoptysis. METHODS: This retrospective study was approved by the institutional review board, and consent was waived. The rates of hemostasis, complications, procedure time, dose-area product, and haemoptysis-free survival were retrospectively compared between primary lung cancer (non-small cell [n = 111] and small cell [n = 11]) patients who underwent BAE using NBCA (n = 58) or PVA particles (n = 64) between January 2004 and December 2019. Predictors of recurrent haemoptysis were analysed using the Cox proportional hazard regression model. RESULTS: Among 122 patients (mean age, 66 ± 10 years; range 32-86 years; 103 men), more patients in the NBCA group (81.0%; 47 of 58) achieved complete hemostasis than did patients in the PVA group (53.1%; 34 of 64) (P = 0.002). No major complications were observed in either group. The procedure time (36.4 ± 21.6 vs. 56.3 ± 27.4 min, P < 0.001) was shorter, and the dose-area product (58.6 ± 64.0 vs. 233.5 ± 225.0 Gy*cm2, P < 0.001) was smaller in the NBCA group than in the PVA group. The median haemoptysis-free survival was 173.0 in the NBCA group compared with 20.0 days in the PVA group (P < 0.001). The PVA use (P < 0.001) and coagulopathy (P = 0.014) were independent predictors of shortened haemoptysis-free survival. CONCLUSION: BAE using NBCA showed significantly superior initial hemostasis with longer haemoptysis-free survival, shorter procedure time, and reduced radiation dose than BAE using PVA particles. The PVA use and coagulopathy were independent predictors of recurrent haemoptysis. TRIAL REGISTRATION: Retrospectively registered.

Incidence and outcomes of adverse drug reactions to first-line anti-tuberculosis drugs and their effects on the quality of life: A multicenter prospective cohort study.

BACKGROUND: In tuberculosis (TB) treatment, adverse drug reactions (ADRs) can interrupt treatment and decrease the quality of life (QoL). We aimed to prospectively investigate the incidence of ADRs to first-line anti-TB drugs and related outcomes and QoL. METHODS: Adult patients with TB who had been treated with first-line anti-TB drugs in five Korean hospitals were enrolled. ADR questionnaire surveys and blood tests were performed four times serially, and QoL was assessed on the fourth TB treatment week (±2 weeks). RESULTS: Of 410 enrolled patients with TB (males, 62%; mean age, 52.1 ± 18.1 years [those aged ≥65 years, 26.6%]), 67.8% experienced any ADRs (≥ grade 2) to TB drugs. The most common ADR was fatigue (53.2%), followed by itching (42.7%) and anorexia (41.7%). Older adult patients experienced relatively more ADRs, including anorexia, dyspepsia, rash, dizziness, anemia, abnormal hepatic/renal function tests, and increased uric acid levels (p < 0.05). Treatment regimens changed for 9.5% of patients owing to ADRs to anti-TB drugs. Patients with any ADRs and older adult patients had significantly lower QoL than their counterparts (p < 0.05). Old age (odds ratio [OR], 1.02) and being male (OR 2.65) were independently associated with ADRs, whereas active smoking (OR 4.73) and a relatively long treatment phase (OR 5.13) were independently associated with hepatotoxicity. CONCLUSION: ADRs to first-line anti-TB drugs were common and related to relatively low QoL, especially among older adults. Although 9.5% of patients had ADR-related regimen changes, most patients with ADRs completed treatments successfully.

Effect of mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease: Randomized controlled trial.

OBJECTIVES: To evaluate the effects of a mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease. METHODS: A randomized controlled design was used. The participants were randomly assigned to an intervention or a control group. The intervention group (n = 20) received mobile health intervention comprising mobile applications, smartwatches, smartphone-based short text messages and information, and telephone counselling; whereas the control group (n = 23) received short text messages and telephone counselling for 16 weeks. RESULTS: After 16 weeks, self-efficacy and non-motor symptom scores in the intervention group significantly improved compared to those in the control group. However, no significant differences were observed in the motor symptoms, self-management, and quality of life between the groups. CONCLUSIONS: The mobile health intervention for self-management is effective for self-efficacy and non-motor symptoms in people with Parkinson's disease.

Usefulness of Contrast-Enhanced CT in a Patient with Acute Phlegmonous Esophagitis: A Case Report and Literature Review.

Acute phlegmonous esophagitis is a very rare, life-threatening form of esophagitis, characterized by diffuse bacterial infection and pus formation within the submucosal and muscularis layers of the esophagus. We describe a case in which contrast-enhanced chest CT was useful for evaluating the severity of phlegmonous esophagitis, which was overlooked and underestimated by endoscopy.

[Oxygen reserve index: a new parameter for oxygen therapy]. / 氧储备指数：氧疗监测的新方法.

Oxygen reserve index (ORI) is a novel dimensionless index used for noninvasive, real-time, and continuous monitoring of oxygenation, and ORI value ranges from 0 to 1, which reflects the range of 100-200 mmHg for arterial partial pressure of oxygen. ORI combined with pulse oximetry may help to accurately adjust the concentration of inspired oxygen and prevent hyperoxemia and hypoxemia. ORI is suitable for various clinical situations, and the medical staff should master this novel parameter and use it properly to assess the oxygenation of patients. In addition, several limitations of ORI should be noticed during clinical application.

[The role and mechanism of autophagy in lipopolysaccharide-induced inflammatory response of A549 cells]. / 自噬在脂多糖诱导的A549ç»†èƒžç‚Žç—‡ååº”ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 µg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 µg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma. METHODS: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. RESULTS: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. CONCLUSION: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.