AIM: To detect the expression of microRNA (miRNA)-29a in pulmonary arteries of monocrotaline (MCT)-induced pulmonary hypertensive rats, and to investigate the effects of miRNA-29a on pulmonary hypertension.METHODS: MCT-induced pulmonary hypertensive model was established in Wistar rats.The expression of miRNA-29a in the lung tissue was determined by qPCR.miRNA-29a was overexpressed in the pulmonary hypertension rats by tail vein injection of miRNA-29a-mimic.Pulmonary artery pressure (PAP) and systemic arterial pressure (SAP) were measured.The morphological changes of the pulmonary arteries were observed by HE staining.The protein levels of p-Akt and p-eNOS were detected by Western blot.RESULTS: The mRNA expression of miRNA-29a was significantly decreased in the pulmonary arteries of MCT-induced pulmonary hypertensive rats.Furthermore, after overexpression of miRNA-29a, PAP was remarkably reduced, while SAP remained unchanged.In addition, the increased thickness of tunica media, the remodeling of pulmonary arteries and the decreased protein levels of p-Akt and p-eNOS in the pulmonary hypertensive rats were dramati-cally changed after miRNA-29a overexpression.CONCLUSION: Overexpression of miRNA-29a ameliorates pulmonary hypertension in rats.These effects may be associated with the activation of PI3K/Akt-eNOS signaling pathway.

OBJECTIVE:To study the pharmacokinetics of hydrochlorothiazide and valsartan in healthy volunteers after single administration of its compound dispersible tablets.METHODS:Plasma concentrations of hydrochlorothiazide and valsartan were determined by HPLC and their pharmacokinetic parameters were calculated with DAS software.RESULTS:The pharmacokinetic parameters of hydrochlorothiazide at low,medium and high doses were as follows:t1/2 were(12.56?3.66),(11.47?5.47) and(11.20?5.03) h,respectively;Cmax were(72.00?19.68),(169.96?52.17) and(203.66?61.41)ng ?mL-1,respectively;AUC0～48 were(592.87?179.44),(1 155.45?252.03) and(1 410.99?331.82) ng?h?mL-1,respectively;AUC0～∞ were(779.76?201.42),(1 246.89?307.03) and(1 482.14?332.20) ng?h?mL-1,respectively.The pharmacokinetic parameters of valsartan at low,medium and high doses were as follows:t1/2 were(7.29?3.10),(8.56?2.22) and(8.62?2.86)h,respectively;Cmax were(2.12?0.65),(6.76?2.08) and(6.71?2.59)ng ?mL-1,respectively;AUC0～48 were(18.16?4.52),(41.77?10.86) and(51.77?27.45) ng?h?mL-1,respectively;AUC0～∞ were(19.07?5.56),(42.60?11.18) and(53.49?26.93) ng?h?mL-1 respectively.CONCLUSION:The pharmacokinetics for compound valsartan dispersible tablet fitted linear kinetics process.There is no interaction in pharmacokinetics between hydrochlorothiazide and valsartan when they used in combination.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Male ; Middle Aged ; Paraquat ; poisoning ; urine ; Prognosis ; Young Adult

OBJECTIVE: To investigate the effect of short-term rehabilitation therapy based on exercise on lung function in coal workers' with pneumoconiosis(CWP). METHODS: A total of 74 CWP patients were divided into control group(32) and treatment group(42) by random number table method. The control group received routine treatment only. The treatment group underwent 6 months of exercise-based rehabilitation treatment on the basis of routine treatment. The lung function was assessed in two groups to evaluate the treatment efficacy. RESULTS: Before rehabilitation treatment, the vital capacity(VC) and forced vital capacity(FVC) of patients in the treatment group were lower than that in the control group(P<0.05). But there was no significant difference in forced expiratory volume in first second(FEV_(1.0)) and FEV_(1.0)% between the two groups(P>0.05). After treatment, VC and FVC in the treatment group were higher than that before treatment in the same group(P<0.05). However, there was no significant difference in the four lung function indexes before and after treatment in the control group(P>0.05). The difference of VC and FVC before and after treatment in the treatment group was higher than those in the control group(P<0.01). However, there was no significant difference in FEV_(1.0 )and FEV_(1.0)% between the two groups before and after treatment(P>0.05). CONCLUSION: Exercise-based short-term rehabilitation therapy can improve lung ventilation of CWP patients.

Background Diagnosis of pneumoconiosis by radiologist reading chest X-ray images is affected by many factors and is prone to misdiagnosis/missed diagnosis. With the rapid development of artificial intelligence in the field of medical imaging, whether artificial intelligence can be used to read images of pneumoconiosis deserves consideration. Objective Three deep learning models for identifying presence of pneumoconiosis were constructed based on deep convolutional neural network. An optimal model was selected by comparing diagnostic efficiency of the three models. Methods Digital radiography (DR) chest images were collected between June 2017 and December 2020 from 7 hospitals and standard radiograph quality control protocol was also followed. The DR chest images with positive results were classified into the positive group, while those without pneumoconiosis were classified into the negative group. The collected chest radiographs were labeled by experts who had passed the assessment of reading radiographs,and the experts were constantly assessed for consistency in the labeling process based on an expectation-maximization algorithm. The labeled data were cleaned, archived, and preprocessed, and then were grouped into a training set and a verification set. Three deep convolutional neural network models TMNet, ResNet-50, and ResNeXt-50 were constructed and trained by ten-fold cross-validation method to obtain an optimal model. Five hundred cases of DR chest radiographs that were not included in the training set and the validation set were collected, and identified by five senior experts as the gold standard, named the test set. The accuracy rate, sensitivity, specificity, area under curve (AUC), and other indexes of the three models were derived after testing, and the efficiency of the three models was evaluated and compared. Results A total of 24867 DR chest radiographs of the training set and the validation set were collected in this study, including 6978 images in the positive group and 17889 images in the negative group. There were 312 cases of pulmonary abnormalities such as pneumothorax and pulmonary tuberculosis. A total of nine experts labeled the chest radiographs, the labeling consistency rate of pneumoconiosis (non-staging) was above 88%, and the labeling consistency rate of pneumoconiosis staging ranged from 84.68% to 93.66%. The diagnostic accuracy, sensitivity, specificity, and AUC of TMNet were 95.20%, 99.66%, 88.61%, and 0.987, respectively. The indicators of ResNeXt were 87.00%, 89.93%, 82.67%, and 0.911, respectively. Those of ResNet were 84.00%, 85.91%, 81.19%, and 0.912, respectively. All these indexes of TMNet were higher than those of ResNeXt-50 and ResNet-50 models. The AUC differences between TMNet and the other two models were both statistically significant (P<0.001). Conclusion All the three convolutional neural network models can effectively diagnose the presence of pneumoconiosis, among which TMNet provides the best efficiency.

Background Multi-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. Objective To present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. Methods From June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. Results All 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P<0.05). Statistically significant differences in p, q, and r subsets of round nodules were found in patients with pneumoconiosis at different stages (P<0.05). Observed nodule types included solid nodules, pure ground-glass shadow nodules, and partial solid nodules. There were statistically significant differences in pulmonary tuberculosis and bronchiectasis among different stages of coal workers' pneumoconiosis (P<0.05). There were statistically significant differences in interstitial shadows and patches combined with interstitial shadows among different stages of pneumoconiosis complicated with pneumonia (P<0.05). Conclusion MSCT provides images of the progression of coal workers' pneumoconiosis and have a certain relationship with the stages of coal workers' pneumoconiosis, which is conducive to the formulation of reasonable treatment plans in the early clinical stage. Therefore, in the diagnosis and treatment of pneumoconiosis, a great attention should be paid to the imaging technology of chest computerized tomography, especially the use of MSCT examination.

Background At present, the practice of pulmonary rehabilitation for pneumoconiosis in China is in a primary stage. The basis for formulating an individualized comprehensive pulmonary rehabilitation plan is still insufficient, which is one of the factors limiting the development of community-level rehabilitation work. Objective To formulate an exercise prescription based on maximum heart rate measured by cardiopulmonary exercise test (CPET), conduct an individualized comprehensive pulmonary rehabilitation program with the exercise prescription for patients with stable pneumoconiosis, and evaluate its role in improving exercise endurance and quality of life, thus provide a basis for the application and promotion of pulmonary rehabilitation. Methods A total of 68 patients were recruited from the Occupational Disease Prevention Hospital of Jinneng Holding Coal Industry Group Co., Ltd. from April to August 2022 , and were divided into an intervention group and a control group by random number table method, with 34 cases in each group. All the pneumoconiosis patients participated in a baseline test. The control group was given routine drug treatment, while the intervention group received multidisciplinary comprehensive pulmonary rehabilitation treatment on the basis of routine drug treatment, including health education, breathing training, exercise training, nutrition guidance, psychological intervention, and sleep management, whose exercise intensity was determined according to the maximum heart rate provided by CPET. The rehabilitation training lasted for 24 weeks. Patients were evaluated at registration and the end of study respectively. CPET was used to measure peak oxygen uptake per kilogram (pVO₂/kg), anaerobic threshold (AT), carbon dioxide equivalent of ventilation (EqCO₂), maximum metabolic equivalent (METs), and maximum work (W_max). The modified British Medical Research Council Dyspnea Questionnaire (mMRC), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Short Form of Health Survey (SF-36) were used to evaluate the potential effect of the comprehensive pulmonary rehabilitation program. Results Among the included 68 patients, 63 patients were having complete data, then 31 cases were assigned in the control group and 32 cases in the interventional group. Before the intervention, there was no significant difference in pVO₂/kg, AT, EqCO₂, METs, or W_max between the two groups (P>0.05). At the end of the trail, the indicators like pVO₂/kg [(19.81±2.38) mL·(min·kg)⁻¹], AT [(14.48±2.33) mL·(min·kg)⁻¹], METs (5.64±0.69), and W_max [(85.25±14) W] of patients in the intervention group were all higher than those [(13.90±2.37) mL·(min·kg)⁻¹, (11.70±1.94) mL·(min kg)⁻¹, (3.97±0.70), and (61.77±14.72) W, respectively] in the control group (P<0.001); there was no significant difference in EqCO₂ between the two groups (P=0.083). Before the trial, there was no significant difference in mMRC, SAS, SDS, PSQI, or CAT scores between the two groups (P>0.05). At the end of the trail, the mMRC score (1.16±0.57), SAS score (27.93±2.12), SDS score (26.48±1.44), PSQI score (1.08±0.88), and CAT score (4.34±3.28) of patients in the intervention group were lower than those [(2.03±0.83), (35.87±6.91), (34.23±6.65), (5.37±3.03), and (13.87±7.53), respectively] in the control group (P<0.001). The SF-36 scores of bodily pain (94.13±10.72), general health (87.50±5.68), vitality (95.31±5.53), mental health (99.88±0.71), and health changes (74.22±4.42) in the intervention group were higher than those [(71.87±32.72), (65.81±15.55), (74.52±16.45), (86.97±16.56), and (29.84±13.50), respectively] in the control group (P<0.001), and no significant difference was found in social functioning and role emotional scores (P>0.05). Conclusion Comprehensive pulmonary rehabilitation can increase the oxygen intake and exercise endurance of pneumoconiosis patients, ameliorate dyspnea symptoms, elevate psychological state and sleep quality, and improve the quality of life.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Background Pneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. Objective To observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. Methods A total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. Results The dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. Conclusion There are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.