Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.

BACKGROUND: The pathogen responsible for tuberculosis is called Mycobacterium tuberculosis. Its interaction with macrophages has a significant impact on the onset and progression of the disease. METHODS: The respiratory pathway allows Mycobacterium tuberculosis to enter the body's lungs where it battles immune cells before being infected latently or actively. In the progress of tuberculosis, Mycobacterium tuberculosis activates the body's immune system and creates inflammatory factors, which cause tissue inflammation to infiltrate and the creation of granulomas, which seriously harms the body. Toll-like receptors of macrophage can mediate host recognition of Mycobacterium tuberculosis, initiate immune responses, and participate in macrophage autophagy. New host-directed therapeutic approaches targeting autophagy for drug-resistant Mycobacterium tuberculosis have emerged, providing new ideas for the effective treatment of tuberculosis. CONCLUSIONS: In-depth understanding of the mechanisms by which macrophage autophagy interacts with intracellular Mycobacterium tuberculosis, as well as the study of potent and specific autophagy-regulating molecules, will lead to much-needed advances in drug discovery and vaccine design, which will improve the prevention and treatment of human tuberculosis.

Qualitative identification and quantitative comparison of Physochlainae Radix from different regions based on chemometric methods.

Physochlainae Radix (PR) is an essential herbal medicine that has been generally applied for treating cough and asthma. In this study, a comprehensive strategy for quality evaluation of PR from different origins was established by integrating qualitative identification, quantitative analysis, and chemometric methods. A total of 58 chemical components were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), and a sensitive and rapid UHPLC-QqQ-MS/MS method was established for the simultaneous determination of 12 compounds. In addition, multivariate statistical analysis was applied for discriminant analysis to compare the differences among 30 batches of PR samples. The results showed that the 30 batches of PR collected from four provinces could be clustered into three categories, in which scoparone, protocatechuic acid, tropic acid, and scopolin were important components to distinguish the primary and non-primary producing areas, as well as superior and inferior products of PR. Chemometric results were consistent and validated each other, and systematically explained the intrinsic quality characteristics of PR. This study first demonstrated that LC-MS combined with multivariate statistical analysis, provided a comprehensive and effective means for quality evaluation of PR.

MiR-24-1-5p Hinders Malignant Phenotypes of Clear Cell Renal Cell Carcinoma by Targeting SHOX2.

MiRNAs are essential epigenetic modulators that can regulate protein expression. According to the principle of base complementary pairing, miRNA is partially or completely complementary to the 3'-UTR region of its target gene, by which it inhibits the translation of the targeted gene. This study investigated the role of miR-24-1-5p in clear cell renal cell carcinoma (ccRCC). Data in TCGA-KIRC denoted that miR-24-1-5p was under-expressed in ccRCC. Bioinformatics analysis predicted that its target gene was SHOX2, which was significantly expressed in cancer tissues. Dual luciferase assay verified the targeting relationship between miR-24-1-5p and SHOX2. Cell function experiments demonstrated that overexpression of miR-24-1-5p significantly inhibited SHOX2 level and the malignant phenotypes of ccRCC cells. The above results illustrated that miR-24-1-5p/SHOX2 axis was critical for the oncogenesis and development of ccRCC, which might be helpful for us to understand the mechanism and novel therapeutic methods of ccRCC.

INPP4B exerts a dual function in the stemness of colorectal cancer stem-like cells through regulating Sox2 and Nanog expression.

Inositol polyphosphate 4-phosphatase type II (INPP4B), a lipid phosphatase, was identified as a negative regulator of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in several cancers. The expression and biological function of INPP4B in human colorectal cancer (CRC) are controversial, while the role and molecular mechanism of INPP4B in colorectal cancer stem-like cells (CR-CSLCs) remains unclear. Here, we observed that INPP4B expression was markedly decreased in primary non-metastatic CR-CSLCs and increased in highly metastatic CR-CSLCs compared with corresponding control non-CSLCs. INPP4B overexpression inhibited self-renewal, and chemoresistance of primary non-metastatic CR-CSLCs, but exerted the opposite roles in highly metastatic CR-CSLCs in vitro. Similarly, INPP4B knockdown had dual functions in the self-renewal and chemoresistance of different CR-CSLCs. In addition, we demonstrated that INPP4B overexpression suppressed the tumorigenicity of primary non-metastatic CR-CSLCs while induced the tumorigenicity of highly metastatic CR-CSLCs in nude mice. Furthermore, INPP4B was found to modulate the stemness of CR-CSLCs by regulating Sox2 and Nanog expression, which was dependent on PI3K/PTEN/Akt signaling. In conclusion, our results highlight an important role of INPP4B in the stemness of CR-CSLCs for the first time and emphasize INPP4B as a dual therapeutic target for suppressing primary cancer cell proliferation and for preventing metastasis in CRC patients.

Clinical efficacy and safety of aidi injection combination with vinorelbine and cisplatin for advanced non-small-cell lung carcinoma: A systematic review and meta-analysis of 54 randomized controlled trials.

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

One functional variant in the 3'-untranslated region of TLR4 is associated with the elevated risk of ventilator-associated pneumonia in the patients with chronic obstructive pulmonary disease.

The aim of this study was to identify the association polymorphism (rs11536889) in the 3'-untranslated region (3'-UTR) of Toll-like receptors 4 (TLR4) and the risk for ventilator-associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR-1236. Enzyme-linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR-1236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3'-UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC-genotyped cells expressed higher levels of IL-8, IL-6, and tumor necrosis factor alpha (TNF-α) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL-8, IL-6, and TNF-α protein was much higher in the CC group than the GC and GG groups subsequent to stimulation by LPS, and the IL-8, IL-6, and TNF-α protein levels in the GC were grouped much lower compared with the GG group. These findings indicated the regulatory association of miR-1236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3'-UTR of mRNA, which interfere with its interaction with the miR-1236, contributing to the risk of VAP.

Effectiveness and safety of chemotherapy with cytokine-induced killer cells in non-small cell lung cancer: A systematic review and meta-analysis of 32 randomized controlled trials.

BACKGROUND AIMS: Cytokine-induced killer (CIK) cells are the most commonly used cellular immunotherapy for multiple tumors. To further confirm whether chemotherapy with CIK cells improves clinical effectiveness and to reveal its optimal use in non-small cell lung cancer (NSCLC), we systematically reevaluated all relevant studies. METHODS: We collected all studies about chemotherapy with CIK cells for NSCLC from the Medline, Embase, Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Data, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and U.S. clinical trials. We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (version 5.1.0), extracted the data using a standard data extraction form, synthesized the data using meta-analysis and finally rated the evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Thirty-two RCTs with 2250 patients were included, and most trials had unclear risk of bias. The merged risk ratios values and their 95% confidence intervals of meta-analysis for objective response rate, disease control rate, 1- and 2-year overall survival rates, 1- and 2-year progression-free survival rates were as following: 1.45 (1.31-1.61), 1.26 (1.16-.37), 1.42 (1.23-1.63), 2.06 (1.36-3.12), 1.93 (1.38-2.69) and 3.30 (1.13-9.67). Compared with chemotherapy alone, all differences were statistically significant. CIK cells could increase the CD3+ T cells, CD3+ CD4+ T cells, NK cells and the ratio of CD4+/CD8+ T cells. The chemotherapy with CIK cells had a lower risk of hematotoxicity, gastrointestinal toxicity, liver injury and a higher fever than that of chemotherapy alone. The evidence quality was "moderate" to "very low." CONCLUSIONS: The available moderate evidences indicate that chemotherapy with CIK cells, especially autologous CIK cells, can significantly improve the tumor responses, 1- and 2-year overall and progression-free survival rates in patients with advanced NSCLC. This treatment does have a high risk of fever. The optimal use may be treatment with one or two cycles and in combination with vinorelbine and cisplatin, paclitaxel and cisplatin, or docetaxel and cisplatin.

Clinical efficacy and safety of sodium cantharidinate plus chemotherapy in non-small-cell lung cancer: A systematic review and meta-analysis of 38 randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Sodium cantharidinate has been widely used in lung cancer treatment in China. To investigate whether sodium cantharidinate improves clinical effectiveness in non-small-cell lung cancer, we systematically re-evaluated all related studies. METHODS: All studies of cantharidinate for non-small-cell lung cancers (NSCLC) were selected from the MEDLINE, EMBASE, Web of Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US-clinical trials databases (established to September 2017). Their quality was evaluated using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0). The data were extracted following PICO principles and synthesized through meta-analysis. RESULTS AND DISCUSSION: We included 38 trials involving 2845 patients, but most trials had an unclear risk of bias. Sodium cantharidinate could increase the objective response rate (ORR) (1.52, (1.40-1.66]), disease control rate (DCR) (1.20, [1.16-1.25]) and quality of life (QOL) (1.76, [1.56-1.98]), but not the 1-year overall survival (OS) rate (1.16, [0.91-1.47]) and the 2-year OS rate (1.21, [0.51-2.91]). Subgroup analysis revealed that sodium cantharidinate and vitamin B6 at 0.5, 0.4 or 0.3 mg, and cantharidinate at 0.5 mg could all increase the ORR and DCR. Cantharidinate therapy had a lower risk of neutropenia (0.58, [0.50-0.67]), thrombocytopenia (0.57, [0.45-0.72]), gastrointestinal reaction (0.65, [0.52-0.82]) and nausea/vomiting (0.56, [0.41-0.76]) than that of chemotherapy alone. Sensitivity analysis showed that the results had good robustness. WHAT IS NEW AND CONCLUSION: Current evidence reveals that sodium cantharidinate can improve tumour responses and QOL with a lower risk of haematotoxicity and gastrointestinal toxicity than chemotherapy alone in NSCLC. However, the evidence does not indicate that it can improve long-term survival rates.

Quercetin restrains TGF-ß1-induced epithelial-mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression.

Emerging evidence has indicated that transforming growth factor-beta 1 (TGF-ß1) induces the epithelial-mesenchymal transition (EMT) in cancer cells, thus promoting their motility and invasiveness. Quercetin, a member of the polyphenolic flavonoid family, has been reported to display anticancer activity against a broad range of cancer cell types. Indeed, numerous studies have shown the cancer preventive effects and molecular mechanisms of quercetin in vitro using diverse cell model systems. However, the potential effect of quercetin on EMT remains unclear. In this study, we identified a unique function of quercetin in inhibiting the EMT process induced by TGF-ß1. In particular, quercetin rescued the morphological changes and EMT-like phenotypes in TGF-ß1-activated SW480 cells, and this inhibition of TGF-ß1-induced EMT was mediated via the suppression of Twist1 expression. In addition, quercetin strongly suppressed TGF-ß1-induced invasion of SW480 cells. Thus, quercetin may be considered a novel therapeutic agent for the treatment of patients with refractory cancer and for the prevention of the metastatic cascade initiated by EMT.

Peroxiredoxin 2 is upregulated in colorectal cancer and contributes to colorectal cancer cells' survival by protecting cells from oxidative stress.

Peroxiredoxin 2 (Prdx2) is a member of the peroxiredoxin family, which is responsible for neutralizing reactive oxygen species. Prdx2 has been found to be elevated in several human cancer cells and tissues, including colorectal cancer (CRC), and it influences diverse cellular processes involving cells' survival, proliferation, and apoptosis, which suggests a possible role for Prdx2 in the maintenance of cancer cell. However, the mechanism by which Prdx2 modulates CRC cells' survival is unknown. The current study aimed to determine the effect of elevated Prdx2 on CRC cells and to further understand the underlying mechanisms. The results of this study showed that Prdx2 was upregulated in CRC tissues compared with the matched noncancer colorectal mucosa tissues and that Prdx2 expression was positively associated with tumor metastasis and the TNM stage. In the LoVo CRC cell line, Prdx2 was upregulated at both the RNA and protein levels compared with the normal FHC colorectal mucosa cell line. In addition, the LoVo CRC cell line was significantly more resistant to hydrogen peroxide (H2O2)-induced apoptosis because of a failure to activate pro-apoptotic pathways in contrast to Prdx2 knockdown cells. Suppression of Prdx2 using a lentiviral vector-mediated Prdx2-specific shRNA in the LoVo cell line restored H2O2 sensitivity. Our results suggested that Prdx2 has an essential role in regulating oxidation-induced apoptosis in CRC cells. Prdx2 may have potential as a therapeutic target in CRC.

Effect of bufei granule on stable chronic obstructive pulmonary disease: a randomized, double blinded, placebo-controlled, and multicenter clinical study.

OBJECTIVE: To study the therapeutic effect Bufei granule, which is a traditional Chinese drug that can enhance the immune function of the lung, on patients with stable chronic obstructive pulmonary disease (COPD). METHODS: This is a randomized, double blinded, placebo-controlled, and multicenter clinical study. Three medical centers in Tianjin, China, participated in the trial. A total of 140 patients with stable COPD were enrolled and randomized into two groups, with 70 patients in each. The treatment group was treated with Bufei granule, while the control group received Bufei placebo. The pharmacological treatment lasted for 12 weeks from the date of enrollment. Then, the indexes of patients were observed. Data were analyzed to study the effect of Bufei granule, with the frequency of acute exacerbation as the primary outcome. Traditional Chinese Medicine syndromes, Modified British Medical Research Council dyspnea scale score, St. George's respiratory questionnaire scores, pulmonary function, and serum inflammatory marker levels [including interleukin-6 (IL-6), interleukin-8, tumor necrosis factor-alpha, and transformation growth factor-beta1] were the secondary outcomes. RESULTS: During the 12-week treatment, treatment and control groups had no adverse reactions. The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05, except for the level of IL-6. CONCLUSION: Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation, improving the quality of life, and alleviating the severity of inflammation.

Network pharmacology prediction, molecular docking, and molecular dynamics simulation-based strategy to explore the potential mechanism of Huashanshen dripping pill against asthma.

OBJECTIVES: Asthma is a heterogeneous disease characterized by chronic airway inflammation. Huashanshen dripping pills (HSS) are commonly utilized for relieving asthma, relieving cough, and expelling phlegm. At present, the molecular mechanism against airway inflammation remains unclear. METHODS: In this study, network pharmacology, molecular docking technology, and molecular dynamic simulation were used to predict the therapeutic pathways of HSS for asthma. The ovalbumin-induced mouse model was used to further validate the prediction by RT-qPCR, western blot, immunofluorescence, and related methods. KEY FINDINGS: The findings indicate that HSS improves lung function and relieves lung inflammation by reducing inflammatory cell infiltration around the bronchus and reducing eosinophilic counts in bronchoalveolar lavage fluid (BALF). In addition, it lowers the levels of inflammatory cytokines and the expression levels of interleukin-4, interleukin-5, and interleukin-13 mRNA. HSS also inhibits the phosphorylation and nuclear translocation of NF-κB p65 protein. CONCLUSIONS: All results suggested that HSS can decrease airway inflammation in asthmatic mice by inhibiting NF-κB signaling pathway. This finding will shed light on how it can be used to treat asthma.

Defensins: A novel weapon against Mycobacterium tuberculosis?

Tuberculosis (TB) is a serious airborne communicable disease caused by organisms of the Mycobacterium tuberculosis (Mtb) complex. Although the standard treatment antimicrobials, including isoniazid, rifampicin, pyrazinamide, and ethambutol, have made great progress in the treatment of TB, problems including the rising incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the severe toxicity and side effects of antimicrobials, and the low immunity of TB patients have become the bottlenecks of the current TB treatments. Therefore, both safe and effective new strategies to prevent and treat TB have become a top priority. As a subfamily of cationic antimicrobial peptides, defensins are rich in cysteine and play a vital role in resisting the invasion of microorganisms and regulating the immune response. Inspired by studies on the roles of defensins in host defence, we describe their research history and then review their structural features and antimicrobial mechanisms, specifically for fighting Mtb in detail. Finally, we discuss the clinical relevance, therapeutic potential, and potential challenges of defensins in anti-TB therapy. We further debate the possible solutions of the current application of defensins to provide new insights for eliminating Mtb.

Identification of a new risk score model based on hypoxia and EMT-related genes for predicting lung squamous cell carcinoma prognosis.

A complicated analysis of the prognostic characteristics of lung squamous cell carcinoma (LUSC) is needed. The aim of this study was to develop a risk score model to predict immunotherapeutic response and prognosis for patients with LUSC. A hypoxia and epithelial-mesenchymal transition-related risk score model was developed for prediction of LUSC. The correlation between risk score and clinical characteristics was determined. The single sample gene set enrichment analysis algorithm was utilized to determine the abundance of cell infiltration in tumor immune microenvironment in LUSC. The predictive value of risk score model in response to immunotherapy was evaluated. A hypoxia and epithelial-mesenchymal transition-related risk score model was constructed. This risk score model was correlated with the overall survival of LUSC. Patients with low-risk presented a high survival possibility. The high-risk group was involved in ECM receptor interaction, complement and coagulation cascades, intestinal immune network for IgA production. Finally, patients with low-risk score had significant clinical benefit. The risk score model was constructed to predict immunotherapeutic response and prognosis for patients with LUSC. In addition to identifying LUSC patients with poor survival, the results provide more information for the immune immunotherapy and microenvironment for LUSC.

Automatic Multilabel Classification of Multiple Fundus Diseases Based on Convolutional Neural Network With Squeeze-and-Excitation Attention.

Purpose: Automatic multilabel classification of multiple fundus diseases is of importance for ophthalmologists. This study aims to design an effective multilabel classification model that can automatically classify multiple fundus diseases based on color fundus images. Methods: We proposed a multilabel fundus disease classification model based on a convolutional neural network to classify normal and seven categories of common fundus diseases. Specifically, an attention mechanism was introduced into the network to further extract information features from color fundus images. The fundus images with eight categories of labels were applied to train, validate, and test our model. We employed the validation accuracy, area under the receiver operating characteristic curve (AUC), and F1-score as performance metrics to evaluate our model. Results: Our proposed model achieved better performance with a validation accuracy of 94.27%, an AUC of 85.80%, and an F1-score of 86.08%, compared to two state-of-the-art models. Most important, the number of training parameters has dramatically dropped by three and eight times compared to the two state-of-the-art models. Conclusions: This model can automatically classify multiple fundus diseases with not only excellent accuracy, AUC, and F1-score but also significantly fewer training parameters and lower computational cost, providing a reliable assistant in clinical screening. Translational Relevance: The proposed model can be widely applied in large-scale multiple fundus disease screening, helping to create more efficient diagnostics in primary care settings.

A novel polyhedral oligomeric silsesquioxane nanohybrid fluorescent sensor designed based on an osmotic mechanism for specific detection and intelligent scavenging of magnesium ions.

BACKGROUND: Mg2+ has long been recognized as one of the most vital cations due to its diverse physiological and pathological roles, making it indispensable in both biomedical and biological research. Organic fluorescent sensors are commonly employed for Mg2+ detection, but they often lack high selectivity and exhibit poor hydrophilicity, limiting their biomedical applications. RESULTS: Herein, we introduced a novel organic-inorganic hybrid fluorescence sensor, PFHBS, constructed on the POSS nanoplatforms. The efficient connection between PEGylated POSS and the small molecule sensor FHBS through Click chemistry enhances the selectivity and reduces interference, making this chemical sensor ideal for the accurate detection of Mg2+. Furthermore, the incorporation of POSS amplifies the ligand field effect of FHBS, making it more conducive to Mg2+ capture. The modification of PEG chains enhances the sensor's amphiphilicity, facilitating efficient cell penetration and effective Mg2+ detection at the biological level. SIGNIFICANCE: Finally, relying on spontaneous permeation, coupled with its strong ligand field effect and excellent cell permeability, the chemosensor demonstrates the capability to intelligently remove excess Mg2+ from the body. It has been successfully applied to mitigate renal overload resulting from acute Mg2+ poisoning.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

Automatic generation of retinal optical coherence tomography images based on generative adversarial networks.

SIGNIFICANCE: The automatic generation algorithm of optical coherence tomography (OCT) images based on generative adversarial networks (GAN) can generate a large number of simulation images by a relatively small number of real images, which can effectively improve the classification performance. AIM: We proposed an automatic generation algorithm for retinal OCT images based on GAN to alleviate the problem of insufficient images with high quality in deep learning, and put the diagnosis algorithm toward clinical application. APPROACH: We designed a generation network based on GAN and trained the network with a data set constructed by 2014_BOE_Srinivasan and OCT2017 to acquire three models. Then, we generated a large number of images by the three models to augment age-related macular degeneration (AMD), diabetic macular edema (DME), and normal images. We evaluated the generated images by subjective visual observation, Fréchet inception distance (FID) scores, and a classification experiment. RESULTS: Visual observation shows that the generated images have clear and similar features compared with the real images. Also, the lesion regions containing similar features in the real image and the generated image are randomly distributed in the image field of view. When the FID scores of the three types of generated images are lowest, three local optimal models are obtained for AMD, DME, and normal images, indicating the generated images have high quality and diversity. Moreover, the classification experiment results show that the model performance trained with the mixed images is better than that of the model trained with real images, in which the accuracy, sensitivity, and specificity are improved by 5.56%, 8.89%, and 2.22%. In addition, compared with the generation method based on variational auto-encoder (VAE), the method improved the accuracy, sensitivity, and specificity by 1.97%, 2.97%, and 0.99%, for the same test set. CONCLUSIONS: The results show that our method can augment the three kinds of OCT images, not only effectively alleviating the problem of insufficient images with high quality but also improving the diagnosis performance.

Luteolin inhibits viability, migration, angiogenesis and invasion of non-small cell lung cancer vascular endothelial cells via miR-133a-3p/purine rich element binding protein B-mediated MAPK and PI3K/Akt signaling pathways.

Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.