Discovering the link between IL12RB1 gene polymorphisms and tuberculosis susceptibility: a comprehensive meta-analysis.

Introduction: Numerous studies suggest that the risk of tuberculosis (TB) is linked to gene polymorphisms of the interleukin-12 receptor b subunit 1 (IL12RB1), but the association between IL12RB1 polymorphisms and TB susceptibility has not been thoroughly investigated. Methods: A meta-analysis was conducted based on eight case-control studies with 10,112 individuals to further explore this topic. A systematic search of PubMed, Web of Science, Excerpt Medica Database, and Google Scholar up until April 6th, 2023 was performed. ORs and 95% CIs were pooled using the random-effect model. The epidemiological credibility of all significant associations was assessed using the Venice criteria and false-positive report probability (FPRP) analyses. Results: The IL12RB1 rs11575934 and rs401502 showed solid evidence of no significant association with TB susceptibility. However, a weak association was observed between the IL12RB1 rs375947 biomarker and pulmonary tuberculosis (PTB) susceptibility (OR = 1.64, 95% CI: 1.22, 2.21). Discussion: These findings should be confirmed through larger, better-designed studies to clarify the relationship between biomarkers in IL12RB1 gene and different types of TB susceptibility.

[Analysis of Risk Factors of Chronic Pulmonary Heart Disease in Patients With Pneumoconiosis]. / å°˜è‚ºç— æ‚£è€ å‘ç”Ÿæ ¢æ€§è‚ºå¿ƒç— çš„å±é™©å› ç´ åˆ†æž.

Objective: To explore the risk factors for developing chronic pulmonary heart disease in patients with pneumoconiosis. Methods: The medical records of pneumoconiosis patients admitted to an occupational disease hospital in Sichuan Province between January 2012 and November 2021 were collected. Kaplan-Meier (K-M) method, or product-limit method, was used to plot the incidence curves of pulmonary heart disease in the pneumoconiosis patients. Cox proportional hazard regression model was used to analyze the influencing factors associated with chronic pulmonary heart disease in patients with pneumoconiosis. Results: A total of 885 pneumoconiosis patients were included in this study. The follow-up time was 12 to 115 months and the median follow-up time was 43 months. A total of 138 patients developed chronic pulmonary heart disease and the incidence density of pulmonary heart disease was 38.50/1000 person-years. Multivariate Cox proportional hazard regression analysis showed that the influencing factors of pneumoconiosis inpatients developing chronic pulmonary heart disease included the following, being 50 and older (hazard ratio [HR]=1.85, 95% confidence interval [CI]: 1.25-2.74), stage Ⅲ pneumoconiosis (HR=2.43, 95% CI: 1.48-4.01), resting heart rate≥100 beats/min (HR=2.62, 95% CI: 1.63-4.21), the complication of chronic obstructive pulmonary disease (COPD) (HR=4.52, 95% CI: 2.12-9.63), underweight (HR=2.40, 95% CI: 1.48-3.87), overweight and obesity (HR=0.54, 95% CI: 0.34-0.86), and triacylglycerol (TG) (HR=0.69, 95% CI: 0.49-0.99). Conclusion: Old age, stage Ⅲ pneumoconiosis, high resting heart rate, low BMI, and the complication of COPD are risk factors for chronic pulmonary heart disease in pneumoconiosis patients, while overweight and obesity and TG are protective factors. Early identification of the risk factors and the adoption of the corresponding prevention measures are the key to preventing chronic pulmonary heart disease in patients with pneumoconiosis.

Increased m6A-RNA methylation and demethylase FTO suppression is associated with silica-induced pulmonary inflammation and fibrosis.

Silicosis is a severe worldwide occupational hazard, characterized with lung tissue inflammation and irreversible fibrosis caused by crystalline silicon dioxide. As the most common and abundant internal modification of messenger RNAs or noncoding RNAs, N6-methyladenosine (m6A) methylation is dysregulated in the chromic period of silicosis. However, whether m6A modification is involved in the early phase of silica-induced pulmonary inflammation and fibrosis and its specific effector cells remains unknown. In this study, we established a pulmonary inflammation and fibrosis mouse model by silica particles on day 7 and day 28. Then, we examined the global m6A modification level by m6A dot blot and m6A RNA methylation quantification kits. The key m6A regulatory factors were analyzed by RTqPCR, Western blot, and immunohistochemistry (IHC) in normal and silicosis mice. The results showed that the global m6A modification level was upregulated in silicosis lung tissues with the demethylase FTO suppression after silica exposure for 7 days and 28 days. METTL3, METTL14, ALKBH5, and other m6A readers had no obvious differences between the control and silicosis groups. Then, single-cell sequencing analysis revealed that thirteen kinds of cells were recognized in silicosis lung tissues, and the mRNA expression of FTO was downregulated in epithelial cells, endothelial cells, fibroblasts, and monocytes. These results were further confirmed in mouse lung epithelial cells (MLE-12) exposed to silica and in the peripheral blood mononuclear cells of silicosis patients. In conclusion, the high level of global m6A modification in the early stage of silicosis is induced by the downregulation of the demethylase FTO, which may provide a novel target for the diagnosis and treatment of silicosis.

Crosstalk between microbial biofilms in the gastrointestinal tract and chronic mucosa diseases.

The gastrointestinal (GI) tract is the largest reservoir of microbiota in the human body; however, it is still challenging to estimate the distribution and life patterns of microbes. Biofilm, as the predominant form in the microbial ecosystem, serves ideally to connect intestinal flora, molecules, and host mucosa cells. It gives bacteria the capacity to inhabit ecological niches, communicate with host cells, and withstand environmental stresses. This study intends to evaluate the connection between GI tract biofilms and chronic mucosa diseases such as chronic gastritis, inflammatory bowel disease, and colorectal cancer. In each disease, we summarize the representative biofilm makers including Helicobacter pylori, adherent-invasive Escherichia coli, Bacteroides fragilis, and Fusobacterium nucleatum. We address biofilm's role in causing inflammation and the pro-carcinogenic stage in addition to discussing the typical resistance, persistence, and recurrence mechanisms seen in vitro. Biofilms may serve as a new biomarker for endoscopic and pathologic detection of gastrointestinal disease and suppression, which may be a useful addition to the present therapy strategy.

Microfluidic Chip with Two-Stage Isothermal Amplification Method for Highly Sensitive Parallel Detection of SARS-CoV-2 and Measles Virus.

A two-stage isothermal amplification method, which consists of a first-stage basic recombinase polymerase amplification (RPA) and a second-stage fluorescence loop-mediated isothermal amplification (LAMP), as well as a microfluidic-chip-based portable system, were developed in this study; these enabled parallel detection of multiplex targets in real time in around one hour, with high sensitivity and specificity, without cross-contamination. The consumption of the sample and the reagent was 2.1 µL and 10.6 µL per reaction for RPA and LAMP, respectively. The lowest detection limit (LOD) was about 10 copies. The clinical amplification of about 40 nasopharyngeal swab samples, containing 17 SARS-CoV-2 (severe acute respiratory syndrome coronavirus) and 23 measles viruses (MV), were parallel tested by using the microfluidic chip. Both clinical specificity and sensitivity were 100% for MV, and the clinical specificity and sensitivity were 94.12% and 95.83% for SARS-CoV-2, respectively. This two-stage isothermal amplification method based on the microfluidic chip format offers a convenient, clinically parallel molecular diagnostic method, which can identify different nucleic acid samples simultaneously and in a timely manner, and with a low cost of the reaction reagent. It is especially suitable for resource-limited areas and point-of-care testing (POCT).

The value of KL-6 in the diagnosis and assessment of interstitial lung disease.

OBJECTIVE: To investigate the value of Krebs von den Lungen-6 (KL-6) in the diagnosis and activity assessment of interstitial lung disease (ILD). METHODS: The data of 69 ILD patients admitted to our hospital from January 2018 to January 2020 were analyzed retrospectively, and they were included in the ILD group. In addition, 69 patients with connective tissue disease (CTD) admitted to our hospital during the same period were selected and included in the non-ILD (NILD) group. The lung function, pulmonary imaging scores, and KL-6 expression levels were compared between the two groups. The patients in the ILD group were divided into two subgroups: the inactive group and the active group. The pulmonary function, pulmonary imaging scores, and the KL-6 expression levels of the patients in the two subgroups were compared. The value of KL-6 in the diagnosis and the ILD activity evaluation were analyzed. RESULTS: The FEV1, FVC, and DLCO levels in the LID group were lower than they were in the NLID group (P<0.05). The LUS and Warrick scores in the LID group were higher than they were in the NLID group (P<0.05). The FEV1, FVC, and DLCO levels in the active group were lower than they were in the inactive group (P<0.05). The LUS and Warrick scores in the active group were higher than they were in the NLID group (P<0.05). The patients' serum KL-6 levels in the ILD group were higher than they were in the NILD group (P<0.05), and the patients' serum KL-6 levels in the ILD group were higher than they were in the inactive group (P<0.05). The Youden's index of serum KL-6 for the diagnosis of ILD was 421.775 U/ml and the sensitivity and specificity of the serum KL-6 were 91.304% and 95.652%, respectively, showing a high diagnostic value (P<0.05). The Youden's index of the serum KL-6 levels for the evaluation of the ILD activity was den Lungen-6 (KL-, with a sensitivity of 60.976% and a specificity of 100%, showing a moderate evaluation value (P<0.05). CONCLUSION: KL-6 has a high value in the diagnosis of interstitial lung disease, and a moderate value in the assessment of interstitial lung disease activity.

QuEChERS with Ultrasound-Assisted Extraction Combined with High-Performance Liquid Chromatography for the Determination of 16 Polycyclic Aromatic Hydrocarbons in Sediment.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have attracted worldwide attention due to their carcinogenic, teratogenic, and mutagenic effects, environmental persistence, and bioaccumulation characteristics. Therefore, the sensitive, reliable, and rapid detection of PAHs in sediment is of great importance. OBJECTIVE: To develop a high-performance liquid chromatography (HPLC) with fluorescence and ultraviolet detection after Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) treatment for simultaneous determination of 16 U.S. Environmental Protection Agency priority PAHs in sediment samples. METHOD: The samples were ultrasonically extracted with acetone and then the supernatant was purified with a modified QuEChERS method. After centrifugation, the supernatant was injected into the HPLC system for analysis. The separation was accomplished on a ZORBAX Eclipse PAH column (150 × 4.6 mm, 3.5 µm) and the column temperature was set at 30 °C. The flow rate of the mobile phase consisting of water and acetonitrile in gradient elution mode was fixed at 0.9 mL/min. Detection was conducted on an ultraviolet detector and a fluorescence detector simultaneously. The qualitative analysis was based on retention time and the quantification was based on standard curves. RESULTS: Under the optimal conditions, this method showed good linearities in the range of 10-200 µg/L with correlation coefficients greater than 0.9993. The method had LODs ranging from 0.00108 to 0.314 ng/g. The mean recoveries ranged from 78.4 to 117% with intra-day and inter-day RSDs of 0.592-10.7% and 1.01-13.0%, respectively. The proposed method was successfully applied to the detection of 16 PAHs in sediment samples collected from the Funan River in Chengdu, China with total contents of 431-2143 ng/g·dw. CONCLUSIONS: The established method is simple, rapid, environmentally friendly, and cost-effective. It can be applied to the analysis of 16 PAHs in sediment samples. HIGHLIGHTS: A method of QuEChERS with ultrasound-assisted extraction combined with HPLC has been established for the analysis of 16 PAHs in sediment samples and the proposed method has been successfully applied to the analysis PAHs in real sediment samples.

Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition.

Pulmonary fibrosis (PF) is a disease that is characterized by abnormal epithelial-mesenchymal transition (EMT) and persistent inflammatory injury, with high mortality and poor prognosis, but the current therapies are accompanied by certain adverse side effects. In this study, we investigated the role of galangin (GA), an anti-inflammatory and anti-tumoral phytochemical extracted from galangal, in preventing and curing bleomycin (BLM)-induced pulmonary fibrosis and the underlying mechanism. Histopathological staining confirmed that GA dramatically moderated bleomycin-induced pulmonary fibrosis in mice. Compared with the vehicle treatment, GA treatment inhibited the expression of vimentin and increased the expression of E-cadherin. The expression of α-Smooth muscle actin (α-SMA), which is a myofibroblast marker, was also suppressed. In addition, GA diminished the increase in the numbers of CD4+CD69+ and CD8+CD69+ T cells and dendritic cells induced by bleomycin, and reduced the residence of inflammatory cells in the lung tissues. Notably, GA inhibited the TGF-ß1-induced EMT and fibroblast differentiation in vitro, which further confirmed the potential protective effect of GA on pulmonary fibrosis. Taken together, our results suggest that GA exerts a beneficial effect on bleomycin-induced pulmonary fibrosis by attenuating EMT and inflammatory damage and may have prevent potential of pulmonary fibrosis.

[Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with ß-Glucan].

OBJECTIVE: To provide a scientific evaluation of the food safety of the rice biofortified with ß-glucan. METHODS: The acute toxicity and genotoxicity of the rice were evaluated by 14-day feeding experiment, Ames experiment, erythrocyte micronucleus test and mouse lymphoma thymidine kinase gene ( TK) mutation assay respectively. RESULTS: In the acute toxicity test, there was no obvious toxicity of rice biofortified with ß-glucan, and no abnormality was found in anatomical observation. The median lethal dose (LD 50) to rats and mice wereall greater than 15 mg/kg, which belonged to the actual non-toxic level. Whether with S 9 activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. No induction of polychromatic erythrocytes and inhibition of bone marrow were found in erythrocyte micronucleus test. The results of TK gene mutation assay did not show the mutagenicity of ß-glucan bioaugmentation rice. All results of the three genotoxicity tests were negative. CONCLUSION: Under the current experimental conditions, ß-glucan biofortified rice showed no obvious acute toxicity and genotoxicity.

[Association of oxidative stress and serum adiponectin in patients with metabolic syndrome].

OBJECTIVE: To analyze the correlation between oxidative stress and serum adiponectin in patients with metabolic syndrome (MS). METHODS: A total of 126 patients with metabolic syndrome were recruited in the study, and 98 healthy physical examinees with normal serum glucose, lipids, liver function and kidney function were matched with the patients in age and sex and served as controls. The serum total adiponectin(Total-Ad), high molecular weight adiponectin (HMW-Ad) and indexes of oxidative stress [reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA)] of the participants were determined. The correlations between adiponectin (Total-Ad and HMW-Ad) and the indexes of oxidative stress in the patients and the controls were determinaed by multiple linear regressions. RESULTS: Compared with the controls, the patients had decreased Total-Ad [(3.51+/-0.83) microg/mL vs (4.34+/-0.98) microg/mL], HMW-Ad [(1.32+/-0.42) microg/mL vs (2.15+/-0.85) microg/mL] and GSH [(1.15+/-0.54) micromol/L vs (1.96+/-0.62) micromol/L], and increased GSSG [(1.20+/-0.47) micromol/L vs (0.90+/-0.23) micromol/L] and MDA [(6.92+/-1.50) nmol/L vs (4.05+/-0.65) nmol/L] (P<0.05). For the patients, total-Ad and HMW-Ad were positively correlated with GSH, with a partial correlation coefficient of 0.587 and 0.480 respectively (P<0.05), and negatively correlated with MDA, with a partial correlation coefficient of -0.222 and -0.389 respectively (P<0.05). For the controls, no correlations between adiponectin and oxidative stress indexes were found (P<0.05). CONCLUSION: Oxidative stress accompanies MS patients. Adiponectin has a better correlation with GSH than the other indexes, which can serve as an index of oxidative stress. Hypoadiponectinemia correlates closely with oxidative stress in patients with MS.