Diagnosis of mycobacterium avium complex infection utilizing metagenomics next-generation sequencing: a case report.

Mycobacterium avium-intracellulare complex (MAC) is a type of nontuberculous mycobacteria (NTM) and is associated with underlying pulmonary diseases, such as chronic obstructive pulmonary disease, bronchiectasis, chronic aspiration or recurrent pneumonia, inactive or active tuberculosis, pneumoconiosis, and bronchogenic carcinoma. The risk factors for NTM-PD include host, drug, and environmental factors. In this report, we present the case of a 61-year-old man who developed bilateral lung nodules and was experiencing severe hemoptysis. The repeat acid-fast bacilli test performed on both sputum and bronchoalveolar lavage fluid (BALF) samples showed a negative result, as did the GeneXpert test. We employed metagenomic next-generation sequencing (mNGS) to analyze the lung nodule and BALF samples collected from the patient. Both samples tested positive for MAC within 3 days. In addition, traditional MAC culture, conducted for 2 months, confirmed the growth of MAC in the patient's BALF. Then, the patient was treated accordingly. Following treatment, a high-resolution chest computed tomography scan revealed a significant reduction in lung nodules of the patient after 2 months. These results indicate that MAC-associated lung nodules were responsible for the patient's symptoms, emphasizing the need for vigilance in diagnosing MAC infection in the patient without predisposing conditions. Furthermore, these results highlight the potential utility of mNGS as a promising rapid diagnostic tool for MAC infection and its potential role in the diagnosis of NTM disease.

The moderating effect of resting heart rate variability on the relationship between internet addiction tendency and brain morphology.

Previous neuroimaging studies have investigated brain morphology associated with internet addiction tendency (IAT) in healthy subjects. However, whether resting vagally-mediated heart rate variability (HRV) exerting influences on the association of IAT and brain morphology remains unclear. This study used voxel-based morphometry (VBM) and multiple regression analyses to assess the interaction effect of IAT and resting vagally-mediated HRV on regional grey matter volumes in 82 healthy subjects. To further illustrate the observed interaction effect, the moderated hierarchical regression analysis was performed. The results showed that resting vagally-mediated HRV moderated the relationship between IAT scores and grey matter volume (GMV) in the precuneus and cerebellum. Specifically, individuals with higher resting vagally-mediated HRV showed a significant positive relationship between IAT scores and GMV in the precuneus, whereas individuals with lower resting vagally-mediated HRV showed a significant negative relationship between IAT scores and GMV in the precuneus. In addition, IAT scores were negatively correlated with GMV in the cerebellum among individuals with lower resting vagally-mediated HRV, but not among individuals with higher resting vagally-mediated HRV. These findings have demonstrated a moderating role of resting vagally-mediated HRV on the association of IAT and brain morphology.

Flavokawain A ameliorates pulmonary fibrosis by inhibiting the TGF-ß signaling pathway and CXCL12/CXCR4 axis.

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease characterized by myofibroblast proliferation and extracellular matrix deposition that has a high mortality rate and limited therapeutic options. Flavokawain A(FKA) is the major component of chalcone in kava extract. FKA has been reported to inhibit TGF-ß1-induced cardiomyocyte fibrosis by suppressing ROS production in A7r5 cells, but the role and mechanism of FKA in pulmonary fibrosis are unknown. In this study, we evaluated the effect of FKA on pulmonary fibrosis using an animal model of bleomycin-induced pulmonary fibrosis and showed that FKA alleviated the development of pulmonary fibrosis in a dose-dependent manner and improved lung function as well as collagen deposition and extracellular matrix accumulation in mice. In vitro studies showed that FKA inhibited myofibroblast activation and lung fibrosis progression by inhibiting TGF-ß1/Smad signaling in a dose-dependent manner. In addition, we identified CXCL12 as a potential target of FKA through target prediction. Molecular docking, CETSA(cellular thermal displacement assay) and silver staining assays further demonstrated that FKA could interact with CXCL12 and that FKA could inhibit CXCL12 dimerization in vitro. Further analysis revealed that FKA could inhibit fibroblast activation and reduce extracellular matrix (ECM) production and collagen deposition by blocking CXCL12/CXCR4 signaling, and knocking down CXCR4 expression could weaken the inhibitory effect of FKA on CXCL12/CXCR4 signal transduction. In conclusion, our study showed that FKA inhibited CXCL12/CXCR4 signaling by inhibiting CXCL12 dimerization, blocked the CXCL12/CXCR4 signaling pathway and inhibited the TGF-ß1-mediated signaling pathway to ameliorate pulmonary fibrosis, and FKA is a promising therapeutic agent for pulmonary fibrosis.

The impact of sensation seeking personality trait on acute alcohol-induced disinhibition.

BACKGROUND: Acute alcohol-related behavioral disinhibition has been well studied. But whether individual differences in the personality trait sensation seeking affect alcohol-induced behavioral disinhibition remains uncertain. METHODS: The present study used functional near-infrared spectroscopy (fNIRS) technique and a response inhibition task (i.e., Go/No-Go) to determine the impact of the sensation seeking trait on the relationship between acute alcohol administration and inhibitory control capacity, and further investigate the neural mechanisms underlying this behavioral effect. Twenty-five high-sensation seekers and twenty-six low-sensation seekers were enrolled in this study. These participants attended two sessions: once for alcohol intake (0.5g/kg) and once for placebo intake (0g/kg). RESULTS: Our results showed that high-sensation seekers relative to low-sensation seekers showed a significant decrease in inhibition accuracy under alcohol versus the placebo condition. Moreover, reduced prefrontal activity following acute alcohol consumption was more pronounced in high-sensation seekers compared with low-sensation seekers. CONCLUSIONS: These findings showed that alcohol-induced behavioral disinhibition was affected by the personality trait sensation seeking and that recruitment of the prefrontal cortex contributed to the observed behavioral effect.

FOXO3 regulates Smad3 and Smad7 through SPON1 circular RNA to inhibit idiopathic pulmonary fibrosis.

Forkhead box protein O3 (FOXO3) has good inhibition ability toward fibroblast activation and extracellular matrix, especially for the treatment of idiopathic pulmonary fibrosis. How FOXO3 regulates pulmonary fibrosis remains unclear. In this study, we reported that FOXO3 had binding sequences with F-spondin 1 (SPON1) promoter, which can activate its transcription and selectively promote the expression of SPON1 circRNA (circSPON1) but not mRNA expression. We further demonstrated that circSPON1 was involved in the extracellular matrix deposition of HFL1. In the cytoplasm, circSPON1 directly interacted with TGF-ß1-induced Smad3 and inhibited the activation of fibroblasts by inhibiting nuclear translocation. Moreover, circSPON1 bound to miR-942-5p and miR-520f-3p that interfered with Smad7 mRNA and promoted Smad7 expression. This study revealed the mechanism of FOXO3-regulated circSPON1 in the development of pulmonary fibrosis. Potential therapeutic targets and new insights into the diagnosis and treatment of idiopathic pulmonary fibrosis based on circRNA were also provided.

Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar epithelial cell injury and lung fibroblast overactivation. At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. Avitinib (AVB) is a novel oral and potent third-generation tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC). However, the role of avitinib in pulmonary fibrosis has not yet been established. In the present study, we used in vivo and in vitro models to evaluate the role of avitinib in pulmonary fibrosis. In vivo experiments first verified that avitinib significantly alleviated bleomycin-induced pulmonary fibrosis in mice. Further in vitro molecular studies indicated that avitinib inhibited myofibroblast activation, migration and extracellular matrix (ECM) production in NIH-3T3 cells, mainly by inhibiting the TGF-ß1/Smad3 signalling pathways. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation.

Vorapaxar proven to be a promising candidate for pulmonary fibrosis by intervening in the PAR1/JAK2/STAT1/3 signaling pathway-an experimental in vitro and vivo study.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, and its 5-year mortality rate is even higher than the mortality rate of some cancers. Fibrosis can cause irreversible damage to lung structure and function. Treatment options for IPF remain limited, and there is an urgent need to develop effective therapeutic drugs. Protease activated receptor-1 (PAR-1) is a G-protein-coupled receptor and is considered a potential target for the treatment of fibrotic diseases. Vorapaxar is a clinically approved PAR-1 antagonist for cardiovascular protection. The purpose of this study was to explore the potential effect and mechanism of Vorapaxar on pulmonary fibrosis in vivo and in vitro. In the experimental animal model, Vorapaxar can effectively alleviate bleomycin (BLM)-induced pulmonary fibrosis. Treatment with 2.5, 5 or 10 mg/kg Vorapaxar once a day reduced the degree of fibrosis in a dose-dependent manner. The expression of fibronectin, collagen and α smooth muscle actin decreased significantly at the messenger RNA (mRNA) and protein levels in treated mice. In vitro, our results showed that Vorapaxar could inhibit the activation of fibroblasts induced by thrombin in a dose-dependent manner. In terms of mechanism, Vorapaxar inhibits the signal transduction of JAK2/STAT1/3 by inhibiting the activation of protease activated receptor 1, which reduces the expression of HSP90ß and the interaction between HSP90ß and transforming growth factor-ß (TGFß) receptor II and inhibits the TGFß/Smad signaling pathway. In conclusion, Vorapaxar inhibits the activation of pulmonary fibroblasts induced by thrombin by targeting protease activated receptor 1 and alleviates BLM-induced pulmonary fibrosis in mice.

Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.

Zanubrutinib attenuates bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß1 signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease with high mortality and limited treatment. Only two drugs are currently approved for the treatment of IPF, but both have limitations and neither drug could prolong survival time of patients. The etiology of IPF is unclear, but there is growing evidence that B cells and B cell receptor signaling play important roles in the pathogenesis of IPF. Zanubrutinib is a small molecule inhibitor of Bruton's tyrosine kinase (BTK), which is a key enzyme downstream of B cell receptor signaling pathway, has approved for the treatment of mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). While its role in pulmonary fibrosis remains unknown. In this study, we explored the potential effect and mechanisms of zanubrutinib on pulmonary fibrosis in vivo and in vitro. METHODS: In the in vivo experiments, different doses of zanubrutinib were administered in a mouse model of bleomycin-induced pulmonary fibrosis, and pathological manifestations and lung function indices were evaluated. In vitro experiments were performed using TGF-ß1-stimulated fibroblasts to evaluate the effect of zanubrutinib on the activation and autophagy phenotype of fibroblasts and to explore the underlying signaling pathway mechanism. RESULTS: In vivo experiments demonstrated that zanubrutinib effectively attenuated bleomycin (BLM)-induced pulmonary fibrosis in mice. An in vitro mechanistic study indicated that zanubrutinib suppresses collagen deposition and myofibroblast activation by inhibiting the TGF-ß1/Smad pathway and induces autophagy through the TGF-ß1/mTOR pathway. CONCLUSIONS: Zanubrutinib alleviated bleomycin-induced lung fibrosis in mice by inhibiting the TGF-ß1 signaling pathway.

COVID-19 Pandemic and SMEs Performance Decline: The Mediating Role of Management Innovation and Organizational Resilience.

It is a major practical problem to find out a pathway for firms to quickly recover from the performance decline in the context of the COVID-19 pandemic and other sudden major crisis in the current academic circles. Based on event system theory and structural adjustment to regain fit model, this paper empirically explores the impact of the COVID-19 pandemic on SMEs performance decline and discusses the management innovation response and organizational resilience mechanism of firms by virtue of the questionnaire survey data of SMEs in Guangdong Science and Technology Park in China. The research results elucidate that the criticality and disruption of the COVID-19 pandemic will not only lead to the SMEs performance decline, but also enable SMEs to carry out management innovation. Moreover, management innovation does not directly curb the SMEs performance decline caused by the COVID-19 pandemic, but indirectly inhibit it by promoting organizational resilience. In other words, the COVID-19 pandemic will indirectly promote organizational resilience through firm management innovation, thereby curbing the SMEs performance decline. A path of management innovation response and organizational resilience to reverse the performance decline can be obtained in the study when SMEs confronting sudden major crisis. Furthermore, the study also expands the application scope of structural adjustment to regain fit model, which provides a useful reference for firm crisis response and sustainable development.

Neural mechanisms underlying empathy during alcohol abstinence: evidence from connectome-based predictive modeling.

Empathy impairments have been linked to alcohol dependence even during abstinent periods. Nonetheless, the neural underpinnings of abstinence-induced empathy deficits remain unclear. In this study, we employed connectome-based predictive modeling (CPM) by using whole brain resting-state functional connectivity (rs-FC) to predict empathy capability of abstinent alcoholics (n = 47) versus healthy controls (n = 59). In addition, the generalizability of the predictive model (i.e., one group treated as a training dataset and another one treated as a test dataset) was performed to determine whether healthy controls and abstinent alcoholics share common neural fingerprints of empathy. Our results showed that abstinent alcoholics relative to healthy controls had decreased empathy capacity. Although no predictive models were observed in the abstinence group, we found that individual empathy scores in the healthy group can be reliably predicted by functional connectivity from the default mode network (DMN) to the sensorimotor network (SMN), occipital network, and cingulo-opercular network (CON). Moreover, the identified connectivity fingerprints of healthy controls could be generalized to predict empathy in the abstinence group. These findings indicate that neural circuits accounting for empathy may be disrupted by alcohol use and the impaired degree varies greatly among abstinent individuals. The large inter-individual variation may impede identification of the predictive model of empathy in alcohol abstainers.

The Cortico-basal-cerebellar Neurocircuit is Linked to Personality Trait of Novelty Seeking.

Previous neuroimaging studies have highlighted the role of the prefrontal-subcortical circuits in personality trait of novelty seeking (NS), thought to be mediated by the dopaminergic system. However, it remains largely unknown whether cortico-basal-cerebellar connections, heavily influenced by dopamine, are implicated in this temperament dimension as well. The present study aimed to further investigate the relationship between the NS trait and the cortico-basal-cerebellar pathways by using structural covariance network analysis. Ninety-five healthy female volunteers were included in this work, and NS was assessed with the Temperament and Character Inventory (TCI). Our results showed that NS scores were associated with structural connections between the cerebellum and the cerebral cortex, thalamus, and basal ganglia, substantiating the implication of the cortico-basal-cerebellar circuits in the NS construct. In addition, structural connections between visual and sensorimotor regions were also associated with NS scores, indicating that sensory and motor information processing may contribute to NS-related behaviors. Overall, the current findings may deepen our understanding of brain structural circuits related to this temperament dimension.

Functional connectivity-based prediction of global cognition and motor function in riluzole-naive amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder accompanied by cognitive changes. To date, no effective therapy is available for ALS patients, partly due to disease heterogeneity and an imperfect understanding of the underlying pathophysiological processes. Reliable models that can predict cognitive and motor deficits are needed to improve symptomatic treatment and slow down disease progression. This study aimed to identify individualized functional connectivity-based predictors of cognitive and motor function in ALS by using multiple kernel learning (MKL) regression. Resting-state fMRI scanning was performed on 34 riluzole-naive ALS patients. Motor severity and global cognition were separately measured with the revised ALS functional rating scale (ALSFRS-R) and the Montreal Cognitive Assessment (MoCA). Our results showed that functional connectivity within the default mode network (DMN) as well as between the DMN and the sensorimotor network (SMN), fronto-parietal network (FPN), and salience network (SN) were predictive for MoCA scores. Additionally, the observed connectivity patterns were also predictive for the individual ALSFRS-R scores. Our findings demonstrate that cognitive and motor impairments may share common connectivity fingerprints in ALS patients. Furthermore, the identified brain connectivity signatures may serve as novel targets for effective disease-modifying therapies.

Effective connectivity predicts cognitive empathy in cocaine addiction: a spectral dynamic causal modeling study.

Social cognition plays a crucial role in the development and treatment of cocaine dependence. However, studies investigating social cognition, such as empathy and its underlying neural basis, are lacking. To explore the neural interactions among reward and memory circuits, we applied effective connectivity analysis on resting-state fMRI data collected from cocaine-dependent subjects. The relationship between effective connectivity within these two important circuits and empathy ability - evaluated with the Interpersonal Reactivity Index (IRI) - was assessed by machine learning algorithm using multivariate regression analysis. In accordance with the neurocircuitry disruptions of cocaine addiction, the results showed that cocaine-dependent subjects relative to healthy controls had altered resting state effective connectivity between parts of the memory and reward systems. Furthermore, effective connectivity between the memory and reward system could predict the fantasy empathy (FE) subscale scores in cocaine dependence. Overall, our findings provide further evidence for the neural substrates of social cognition in cocaine-dependent patients. These new insights could be useful for the development of new treatment programs for this substance dependency disorder.

Structural covariance of the salience network associated with heart rate variability.

The salience network (SN) anchored by the anterior insula and cingulate is crucial for the autonomic control of body homeostasis. Resting-sate fMRI studies have linked intrinsic SN connectivity with multiple autonomic measures, but little is known about the structural organization of this system relating to cardiac vagal function. To address the above issue, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance of SN with two independent datasets, and then determined whether interregional structural connections within SN related to individual differences in vagally-mediated heart rate variability (HRV). The results showed a significant positive association between structural covariance of the SN and vagal component of HRV in two independent samples. More importantly, the conjunction and pooled data analysis revealed that structural correlation from left anterior insula to dorsal anterior cingulate cortex positively interacted with vagally-mediated HRV. The current results demonstrated a crucial role of the SN in the cortical modulation of efferent vagal activity to the heart, and provided new insight into structural neural network implicated in cardiac vagal control.

Resting state differences between successful and unsuccessful restrained eaters.

Restrained eating is a popular weight loss strategy for young women that tends to have limited effectiveness over extended periods of time. Although previous studies have explored and identified possible personality and behavior differences between successful and unsuccessful restrained eaters (REs), there has been a paucity of research on neurophysiological differences.Towards addressing this gap, we assessed brain resting state (Rs) differences in groups of unsuccessful REs (N = 39) and successful REs (N = 31). In line with hypotheses, unsuccessful REs displayed reduced regional homogeneity in brain regions involved in cognitive control (inferior parietal lobe) compared to successful REs. Regions involved in conflict monitoring (anterior cingulate cortex) were also observed to be comparatively less active in the unsuccessful RE group. Finally, based on analyses of independent components and seed-based functional connectivity, regions involved in conflict monitoring and cognitive control, especially those localized within the frontoparietal network, showed weaker connectivities among unsuccessful REs compared to their successful counterparts.These results underscore specific brain Rs differences between successful REs and unsuccessful REs in regions implicated in cognitive control and conflict monitoring.

[Knockdown of Kruppel like factor 4 (KLF4) promotes RAW264.7 macrophages into M1 polarization].

Objective To investigate the effects of Kruppel like factor 4 (KLF4) gene knockdown on the polarization of RAW264.7 macrophages. Methods KLF4 knockdown lentiviral vector was constructed by RNA interfering. The lentiviral vector was transfected into RAW264.7 cells to realize stable KLF4 gene silencing in RAW264.7 cells. Interleukin-4 (IL-4) was used to stimulate macrophages in wild type group, KLF4 knockdown group and negative control group. The mRNA expression of inducible nitric oxide synthase (iNOS), IL-1ß, tumor necrosis factor α (TNF-α) and Arg1, IL-10, transforming growth factor ß (TGF-ß) of the cells was detected by reverse transcription-PCR. Immunocytochemical staining was used to detect and localize iNOS and Arg1 protein in RAW264.7 cells. Results Levels of iNOS and IL-1ß mRNA in RAW264.7 cells were significantly raised, while levels of Arg1, IL-10 and TGF-ß mRNA were significantly reduced after KLF4 gene knockdown. Levels of KLF4, Arg1, IL-10 and TGF-ß mRNA went up, while the relative levels of iNOS, IL-1ß and TNF-α mRNA went down in wild-type RAW264.7 cells after IL-4 intervention. After shKLF4 group was intervened by IL-4, levels of iNOS, IL-1ß and TNF-α mRNA in shKLF4 group (lentivirus group) were lower than those in wild-type group and higher than those in negative control group. Levels of Arg1, IL-10 and TGF-ß mRNA in shKLF4 group after IL-4 treatment were higher than those in wild-type group, while Arg1 and IL-10 were lower than those in negative control group. Compared with wide-type group, the expression of iNOS protein significantly decreased, while Arg1 protein significantly increased in shKLF4 group 12 hours after IL-4 treatment. Conclusion Knockdown of KLF4 promotes the polarization of RAW264.7 macrophages into M1 as well as inhibits their polarization into M2.

Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis: a randomized, double blind, placebo-controlled and multicenter clinical pilot trial.

OBJECTIVE: To evaluate the effects of Qizhukangxian granules (QG) on idiopathic pulmonary fibrosis (IPF). METHODS: This is a randomized, double blind, placebo-controlled and multicenter clinical pilot trial. Six medical centers in Tianjin, China, participated in the study. A total of 120 IPF patients were enrolled and randomized into two groups, with 60 patients in each group. The treatment group was treated with QG, while the control group received a Qizhukangxian placebo. The pharmacological treatment lasted for 48 weeks from the enrollment date. The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks. Data were analyzed to study the effects of QG; forced vital capacity, change in forced vital capacity and maximal 6-min walk test (6MWT) distance were the primary endpoints. Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF, pulmonary function, changes in pulse oxygen saturation during the 6MWT, dyspnea score, St. George's respiratory questionnaire score, arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score. RESULTS: After 24 weeks of treatment, QG showed greater efficacy than the placebo in certain parameters, including the dyspnea score, Traditional Chinese Medicine symptom pattern score and some indicators in the St. George's respiratory questionnaire score. Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups, except for the maximal distance of the 6MWT and arterial blood gas analyses. No adverse reaction was observed in either group during the 48-week trial treatment period. CONCLUSION: QG could effectively treat IPF patients by ameliorating pulmonary function, improving the quality of life and lowering the percentage of acute exacerbations.

Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: a systematic review and meta-analysis.

BACKGROUND: While antifibrotic drugs significantly decrease lung function decline in idiopathic pulmonary fibrosis (IPF), there is still an unmet need to halt disease progression. Antioxidative therapy with N-acetylcysteine (NAC) is considered a potential additional therapy that can be combined with antifibrotics in some patients in clinical practice. However, data on the efficacy, tolerability, and safety of this combination are scarce. We performed a systematic review and meta-analysis to appraise the safety, tolerability, and efficacy of the combination compared to treatment with pirfenidone alone. METHODS: We systematically reviewed all the published studies with combined pirfenidone (PFD) and NAC (PFD + NAC) treatment in IPF patients. The primary outcomes referred to decline in pulmonary function tests (PFTs) and the rates of IPF patients with side effects. RESULTS: In the meta-analysis, 6 studies with 319 total IPF patients were included. The PFD + NAC group was comparable to the PFD alone group in terms of the predicted forced vital capacity (FVC%) and predicted diffusion capacity for carbon monoxide (DLco%) from treatment start to week 24. Side effects and treatment discontinuation rates were also comparable in both groups. CONCLUSION: This systematic review and meta-analysis suggests that combination with NAC does not alter the efficacy, safety, or tolerability of PFD in comparison to PFD alone in IPF patients.