Fine particulate matter aggravates smoking induced lung injury via NLRP3/caspase-1 pathway in COPD.

BACKGROUND: Exposure to noxious particles, including cigarette smoke and fine particulate matter (PM2.5), is a risk factor for chronic obstructive pulmonary disease (COPD) and promotes inflammation and cell death in the lungs. We investigated the combined effects of cigarette smoking and PM2.5 exposure in patients with COPD, mice, and human bronchial epithelial cells. METHODS: The relationship between PM2.5 exposure and clinical parameters was investigated in patients with COPD based on smoking status. Alveolar destruction, inflammatory cell infiltration, and pro-inflammatory cytokines were monitored in the smoking-exposed emphysema mouse model. To investigate the mechanisms, cell viability and death and pyroptosis-related changes in BEAS-2B cells were assessed following the exposure to cigarette smoke extract (CSE) and PM2.5. RESULTS: High levels of ambient PM2.5 were more strongly associated with high Saint George's respiratory questionnaire specific for COPD (SGRQ-C) scores in currently smoking patients with COPD. Combined exposure to cigarette smoke and PM2.5 increased mean linear intercept and TUNEL-positive cells in lung tissue, which was associated with increased inflammatory cell infiltration and inflammatory cytokine release in mice. Exposure to a combination of CSE and PM2.5 reduced cell viability and upregulated NLRP3, caspase-1, IL-1ß, and IL-18 transcription in BEAS-2B cells. NLRP3 silencing with siRNA reduced pyroptosis and restored cell viability. CONCLUSIONS: PM2.5 aggravates smoking-induced airway inflammation and cell death via pyroptosis. Clinically, PM2.5 deteriorates quality of life and may worsen prognosis in currently smoking patients with COPD.

Customized three-dimensional printed ceramic bone grafts for osseous defects: a prospective randomized study.

Ridge resorption can result in insufficient bone volume for implant surgery, necessitating bone substitutes to restore the resorption area. Recent advances in computer-aided design and manufacturing enable the use of alloplastic bone graft materials with customizable compositions or shapes. This randomized study evaluated the clinical effectiveness of a customized three-dimensional (3D) printed alloplastic bone material. Sixty patients requiring guided bone regeneration for implant installation following tooth extraction due to alveolar bone resorption were recruited at two institutions. The participants were randomly allocated to either a group that received 3D-printed patient-customized bone graft material or a group that received conventional block bone graft material. Implant installation with bone harvesting was performed approximately 5 months after bone grafting. Histological and radiological assessments of the harvested bone area were performed. The experimental group had a significantly higher percent bone volume and a smaller tissue surface than the control group. Bone volume, bone surface, bone surface/volume ratio, bone surface density (bone surface/total volume), and bone mineral density did not differ significantly between groups. Patient-customized bone graft materials offer convenience and reduce patient discomfort. The findings suggest 3D-printed patient-customized bone graft materials could be used as an alternative for simpler bone grafting procedures.

Comparison of intraocular lens power calculation formulas in patients with a history of acute primary angle-closure attack.

BACKGROUND: To compare the accuracy of nine intraocular lens (IOL) power calculation formulas, including three traditional formulas (SRK/T, Haigis, and Hoffer Q) and six new-generation formulas (Barrett Universal II [BUII], Hill-Radial Basis Function [RBF] 3.0, Kane, Emmetropia verifying optical [EVO], Ladas Super, and Pearl-DGS) in patients who underwent cataract surgery after acute primary angle closure (APAC). METHODS: In this retrospective cross-sectional study, 44 eyes of 44 patients (APAC) and 60 eyes of 60 patients (control) were included. We compared the mean absolute error, median absolute error (MedAE), and prediction error after surgery. Subgroup analyses were performed on whether axial length (AL) or preoperative laser peripheral iridotomy affected the postoperative refractive outcomes. RESULTS: In the APAC group, all formulas showed higher MedAE and more myopic shift than the control group (all P < 0.05). In APAC eyes with AL ≥ 22 mm, there were no differences in MedAEs according to the IOL formulas; however, in APAC eyes with AL < 22 mm, Haigis (0.49 D) showed lower MedAE than SRK/T (0.82 D) (P = 0.036) and Hill-RBF 3.0 (0.54 D) showed lower MedAE than SRK/T (0.82 D), Hoffer Q (0.75 D) or Kane (0.83 D) (P = 0.045, 0.036 and 0.027, respectively). Pearl-DGS (0.63 D) showed lower MedAE than Hoffer Q (0.75 D) and Kane (0.83 D) (P = 0.045 and 0.036, respectively). Haigis and Hill-RBF 3.0 showed the highest percentage (46.7%) of eyes with PE within ± 0.5 D in APAC eyes with AL < 22 mm. Iridectomized eyes did not show superior precision than the non-iridotomized eyes in the APAC group. CONCLUSIONS: Refractive errors in the APAC group were more myopic than those in the control group. Haigis and Hill-RBF 3.0 showed high precision in the eyes with AL < 22 mm in the APAC group.

Repeatability and Agreement of Chord Mu between Scheimpflug Tomography and Swept-Source Optical Coherence Tomography.

PURPOSE: To evaluate repeatability and agreement of chord mu between Scheimpflug tomography (Pentacam HR) and sweptsource optical coherence tomography-based optical biometer (IOLMaster 700). METHODS: In this retrospective study, 63 eyes from 33 patients were included. Chord mu, X and Y Cartesian distances between the corneal vertex and the pupil center (Px and Py), and the pupil diameter were compared using two instruments. Repeatability was evaluated using intraclass correlation coefficient (ICC), coefficient of variation (CoV), and within-subject standard deviation (Sw). Interdevice agreement was evaluated using paired t-tests and Bland-Altman plots. RESULTS: Although Sw values for all parameters were similar between the two devices, CoV values of chord mu and pupil diameter were lower, and ICC values of those parameters were higher, in the IOLMaster 700 than in the Pentacam HR. Chord mu and pupil diameter values were higher in IOLMaster 700 than Pentacam HR (p < 0.01). The width of the 95% limit of agreement was wide for all parameters. CONCLUSIONS: IOLMaster 700 showed better repeatability than Pentacam HR in chord mu, Px, Py, and pupil diameter values. Because there were statistically significant differences and a low level of agreement in chord mu and pupil diameter values between the two devices, they cannot be used interchangeably.

Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy.

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.

Superoxide dismutase secreting Bacillus amyloliquefaciens spores attenuate pulmonary fibrosis.

Superoxide dismutase (SOD) can convert active oxygen to oxygen or hydrogen peroxide, and recent research has suggested that it can protect against lung damage and fibrosis. Clinical applications based on SOD remain limited however due to costs and low stability. We here investigated a potential new therapeutic delivery system for this enzyme in the form of SOD-overexpressing Bacillus amyloliquefaciens spores which we introduced into a bleomycin-induced pulmonary fibrosis mouse model. This treatment significantly alleviated the disease, as quantified using a hydroxyproline assay, at 107 colony forming unit (CFU) of Bacillus spores per day. Exposure of the mice to the spores was further found to decrease the lung mRNA levels of CTGF, Col1a1, α-SMA, TGF-ß, TNF-α, and IL-6, and the protein levels of TGF-ß, Smad2/3, αSMA and Col1a1, all major indicators of pulmonary fibrosis. Survival benefits, and reduced byproducts of lipid peroxidase such as malondialdehyde and 4-hydroxynen, were also noted in the treated animals. The beneficial effects of these Bacillus spores on pulmonary fibrosis were further found to be greater than the equivalent free SOD concentration. Immunofluorescence staining of primary pulmonary fibroblasts extracted from the bleomycin-induced model showed decreased αSMA expression following the in vivo treatment with SOD-overexpressing Bacillus. Our treatment approach SOD through Bacillus spores shows beneficial effects against pulmonary fibrosis, combined with the suppression of the SMAD/TGF-ß pathway, suggesting that it is an effective novel delivery route for antioxidants.

You are not lab rats at teaching hospitals: A systematic review of resident and fellow participation leads to improved colonoscopy.

BACKGROUND: Participation in colonoscopies is an essential aspect of endoscopic training. The purpose of this study was to explore the impact of fellow/trainee participation on colonoscopy outcomes. METHODS: This meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). From database inception to July 2022, studies investigating fellow involvement and colonoscopy outcomes were searched across Cochrane library, PubMed, and other databases. The random-effects model was applied to generate more conservative estimates. Sensitive analysis was conducted to explore whether the result would depend on a particular study. Egger's test and Begg's test were used to estimate the potential for publication bias. RESULTS: Seventeen studies including 30,062 participants were included. We found that fellow/trainee involvement enhanced the overall rates of adenoma detection and polyp detection (OR = 1.26, 95% CI = 1.14-1.40, p < 0.001; OR = 1.29, 95% CI = 1.02-1.63, p = 0.020, respectively). The mean number of adenoma/polyps per colonoscopy was also higher with fellow/trainee participation (MD = 0.12, 95% CI = 0.08-0.17, p < 0.001; MD = 0.15, 95% CI = 0.02-0.28, p = 0.020, respectively). CONCLUSION: In addition to its educational purpose, fellow or trainee involvement is associated with beneficial effects on colonoscopy outcomes.

Gut microbiota composition and metabolite profiling in smokers: a comparative study between emphysema and asymptomatic individuals with therapeutic implications.

BACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema. METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation. RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen. CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.

The impact of ambient air pollution on lung function and respiratory symptoms in elite athletes.

BACKGROUND: Air pollution has become a significant public health concern. During exercise, many physiological factors are thought to increase the effects of air pollution. Air pollution most affects lung function and respiratory symptoms. We investigated the association between lung function, respiratory symptoms, and air pollutant concentration with meteorological factors in elite sports athletes. METHODS: A total of 59 elite sports athletes from the Korea National Sports University participated in this prospective, observational study from September 2019 to June 2020. At ten visits, lung function and respiratory symptoms were obtained after a training session. We measured six air pollutants, including SO2, CO, O3, NO2, PM10, and PM2.5, and two meteorological factors, including humidity and temperature. Air pollutants and meteorological factors were measured by two nearest depositories of the national air pollution information system in Korea. RESULTS: In a single-pollutant model, PM2.5, PM10, NO2, and CO were inversely associated with both FEV1 and FEV6, 10 µg/m3 in PM2.5 was associated with a 32.31 mL decrease in FEV1 and a 36.93 mL decrease in FEV6. Meanwhile, O3 and temperature had positive associations with both FEV1 (13.00 and 3.15 mL) and FEV6 (16.91 and 4.76 mL) and humidity with FEV6 (11.98 mL). In the multi-pollutant model at lag 0, FEV1 was associated negatively with O3 and NO2 (-50.68 and -6.87 mL) and positively with SO2 and temperature (65.76 and 8.08 mL). In the multi-pollutant model at lag 6, temperature was associated with FEV1 and FEV6 (6.01 and 8.89 mL). PM2.5, PM10, NO2, CO, and temperature were significantly associated with FEV1 and FEV6 through lag 0-6. CONCLUSIONS: Air pollutants and meteorological factors are associated with lung function and respiratory symptoms and have cumulative effects among elite athletes. In the multi-pollutant model, temperature has the most significant effect on lung function.

The impact of local staging of prostate cancer determined on MRI or DRE at time of radical prostatectomy on progression-free survival: A Will Rogers phenomenon.

INTRODUCTION: We aimed to test whether the current practice of using mpMRI stage might lead to a Will Rogers phenomenon with a stage migration compared to DRE in men undergoing radical prostatectomy. MATERIAL AND METHODS: A total of 572 consecutive patients who underwent radical prostatectomy at a single institution (2007-2017) were included. Clinical stage using digital rectal examination was determined on table by the operating surgeon; mpMRI and pathological stage were recorded after tumor board review. Progression-free survival (PFS) was defined as no rising PSA, no adjuvant/salvage treatment, and no metastases or mortality. PFS was compared between groups and a model incorporating mpMRI into the EAU risk groups was created. RESULTS: Median age was 63 years (IQR 58.5-67) and median PSA was 8.9 ng/ml (IQR 6.5-13.2). Using DRE stage, 20% were NCCN low risk, 43% were intermediate, and 37% high. Median follow-up was 48 months (IQR 22-73). Estimated PFS at 1, 3, and 5 years was 75%, 59%, and 54%, respectively. When comparing PFS between DRE and mpMRI stages, patients deemed T1 (P < 0.01) or T3 (P = 0.03) by mpMRI showed better outcomes than patients staged T1 or T3 by DRE. On univariable analysis lower risk for failure was seen for MRI T1 disease (HR 0.10 95%, CI 0.01-0.73, P = 0.02) or MRI T3 (HR 0.70, CI 0.51-0.97, P = 0.03). On multivariable analysis, only MRI T1 remained a significant predictor (HR 0.08, 95% CI 0.01-0.59, P = 0.01). The subsequent, modified EAU risk model using both DRE and mpMRI performed significantly better than the DRE model. CONCLUSION: PFS based on mpMRI is not the same as DRE staging. Current risk groups which use DRE should be used with caution in whom local stage is based on mpMRI. Our modified EAU-risk categories can provide greater accuracy.

Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose-response meta-analysis.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS: This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

Changes in Diagnostic Performance of Thyroid Cancer Screening before and after the Korean Thyroid Imaging Reporting and Data System Revision.

BACKGROUND: Since the era of "thyroid cancer epidemic," many Korean academic societies discouraged the use of ultrasonography in healthy individuals and revised the Korean Thyroid Imaging Reporting and Data System to address the overscreening and overdiagnosis issues. This study aimed to evaluate the change in the diagnostic effectiveness of thyroid cancer screening over the last decade. METHODS: This single-center, retrospective observational study analyzed the data of 125,962 thyroid nodules obtained during cancer screening at the health promotion center of Seoul National University Bundang Hospital from 2010 to 2019. Only 327 thyroid cancer cases pathologically confirmed by fine-needle aspiration (FNA) were included in the study. The strength of the association between the number of FNA and (1) the number of thyroid cancer diagnoses, (2) the positive predictive values (PPVs), and (3) the difference in PPV from the previous year were evaluated using Pearson's correlation analysis. RESULTS: The number of thyroid FNA biopsies as well as the thyroid cancer diagnoses decreased from 2010 to 2019 (166 to 48 [-71.1%] vs. 43 to 22 [-48.8%]). The PPV of FNA biopsies increased from 25.9% to 45.8% (+76.8%) and was negatively correlated with the number of FNA biopsies performed (R=-0.87, P<0.001). The difference in PPV from the previous year increased similarly but without statistical significance (R=-0.59, P=0.09). CONCLUSION: The diagnostic efficiency of thyroid cancer screening has increased over the last decade, as evidenced by the increasing PPV of FNA biopsies.

The microbiome of lung cancer tissue and its association with pathological and clinical parameters.

Lung cancer is the primary cause of cancer-related deaths worldwide. Recently, although the microbiome has emerged as the key modulator of the carcinogenesis, it has not been evaluated in lung cancer. Here, we evaluated the microbial composition of lung cancer tissues according to the histologic type and genetic mutation, compared it with that of the adjacent normal lung tissues, and investigated the association between the lung microbiome and clinical parameters. We collected lung tissue samples from 162 patients with non-small cell lung cancer (NSCLC, 162 cancer and 54 adjacent normal tissues), surgically resected between January 2018 and December 2019, and analyzed their microbiome using 16S rRNA gene amplicon sequencing, the QIIME2 pipeline, and statistical analyses. NSCLC tissues had significantly lower alpha diversity than the normal tissues, and their microbial composition differed according to the histologic type and cancer genetic mutation. The genera Romboutsia, Novosphingobium, Acinetobacter, and Prevotella were significantly overrepresented in NSCLC tissues. Alpha diversity steadily declined from a normal to a more advanced stage, and microbial compositional differences were noted along with recurrence. Stenotrophomonas was the most predominant genus in the NSCLC tissues of patients with recurrence. The pathways related to the tricarboxylic acid cycle and L-glutamate and L-glutamine biosynthesis were predominant in adenocarcinoma, whereas those related to purine and pyrimidine nucleotide degradation and formaldehyde assimilation were predominant in squamous cell carcinoma. Our findings suggest that the altered lung cancer microbial composition might be associated with cancer initiation and/or progression.

Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique.

A rapid and sensitive diagnosis is crucial for the management of tuberculosis (TB). A simple and label-free approach via homobifunctional imidoesters with a microfluidic platform (SLIM) assay showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples from cases of suspected PTB. Patients with clinically suspected PTB were prospectively enrolled and oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on their clinical features and conventional laboratory results, including the Xpert assay. A total of 272 patients (with TB, n = 128 [47.1%]; without TB, n = 144 [52.9%]; mean age, 59.8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65.6%) was higher than that of the sputum-based Xpert assay (43.4%; P = 0.001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (69.0% [95% CI: 49.2 to 84.7%] versus 7.4% [95% CI: 0.9 to 24.3%]; P = 0.001). The specificity of the SLIM and the Xpert assays was 86.1% (95% CI: 79.3 to 91.3%) and 100% (95% CI: 97.2 to 100%), respectively. When only culture-confirmed cases were analyzed, the SLIM oral swab was comparable to sputum Xpert in sensitivity (64.7% versus 54.3%, P = 0.26). The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases. IMPORTANCE The development of a rapid, accessible, and highly sensitive diagnostic tool is a major challenge in the control and management of tuberculosis. Gene-based diagnostics is recommended for the rapid diagnosis of pulmonary tuberculosis (PTB), but its sensitivity, such as Xpert MTB/RIF assay (Xpert), drops in cases with a low bacterial load. It can only be applied to sputum samples, and it is quite difficult for some patients to produce an adequate amount of sputum. We evaluated the clinical validity of an oral swab-based microfluidic system, i.e., the SLIM assay. The SLIM assay showed a significantly higher sensitivity than the Xpert assay, especially in smear-negative TB cases. This non-sputum-based SLIM assay can be a useful diagnostic test by overcoming the limitations of conventional sputum-based tests in pulmonary TB.

Role of mass spectrometry-based serum proteomics signatures in predicting clinical outcomes and toxicity in patients with cancer treated with immunotherapy.

Immunotherapy has fundamentally changed the landscape of cancer treatment. However, only a subset of patients respond to immunotherapy, and a significant portion experience immune-related adverse events (irAEs). In addition, the predictive ability of current biomarkers such as programmed death-ligand 1 (PD-L1) remains unreliable and establishing better potential candidate markers is of great importance in selecting patients who would benefit from immunotherapy. Here, we focus on the role of serum-based proteomic tests in predicting the response and toxicity of immunotherapy. Serum proteomic signatures refer to unique patterns of proteins which are associated with immune response in patients with cancer. These protein signatures are derived from patient serum samples based on mass spectrometry and act as biomarkers to predict response to immunotherapy. Using machine learning algorithms, serum proteomic tests were developed through training data sets from advanced non-small cell lung cancer (Host Immune Classifier, Primary Immune Response) and malignant melanoma patients (PerspectIV test). The tests effectively stratified patients into groups with good and poor treatment outcomes independent of PD-L1 expression. Here, we review current evidence in the published literature on three liquid biopsy tests that use biomarkers derived from proteomics and machine learning for use in immuno-oncology. We discuss how these tests may inform patient prognosis as well as guide treatment decisions and predict irAE of immunotherapy. Thus, mass spectrometry-based serum proteomics signatures play an important role in predicting clinical outcomes and toxicity.

Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study.

BACKGROUND: Previous studies have confirmed that systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) can predict the prognosis and chemotherapy efficacy of various malignant tumors. However, to the best of our knowledge, no study investigated the SII combined with PNI score to predict the efficacy of anti-programmed death 1 (anti-PD-1) antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in the treatment of locally advanced gastric cancer. This study aims to evaluate the predictive value of pre-treatment SII-PNI score on the sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with locally advanced gastric cancer. METHODS: We registered a prospective clinical study involving 30 locally advanced gastric cancer patients from March 2020 to July 2021. The pre-treatment SII and PNI were calculated from peripheral blood samples, and the cut-off value was calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 568.5) and low PNI (≤ 52.7); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. RESULTS: All patients were evaluated by RECIST1.1 criteria after four cycles of sintilimab immunotherapy combined with XELOX chemotherapy, including 5 patients with TRG 3 and 25 patients with non-TRG 3. The SII-PNI score of non-TRG 3 patients was significantly lower than that of TRG 3 patients (P = 0.017). The medial progression free survival of patients with low SII-PNI score was significantly better than that of patients with high SII-PNI score (P < 0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting progression-free survival (P = 0.003). CONCLUSION: The pre-treatment SII-PNI score is a significant indicator for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy combined with XELOX chemotherapy, which can help to identify high-risk groups and predict prognosis. TRIAL REGISTRATION: The registered name of the trial is "Prospective clinical study of sintilimab combined with chemotherapy for neoadjuvant therapy in locally advanced gastric cancer". Its Current Controlled Trials number is ChiCTR2000030414. Its date of registration is 01/03/2020.

Diagnostic Value, Prognostic Value, and Immune Infiltration of LOX Family Members in Liver Cancer: Bioinformatic Analysis.

Background: Liver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis. Results: The expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC. Conclusions: For LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.

Is metformin use associated with a reduced risk of oesophageal cancer? A systematic review and meta-analysis.

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.

Cadmium induces cytotoxicity in normal mouse renal MM55.K cells.

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨm) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨm loss, and apoptotic cell death in normal mouse renal cells.