Objective To explore the interventional mechanism of Bufei Yishen formula on chronic obstructive pulmonary disease from pathway level.Methods Macrophage inflammatory model was established by LPS stimulation.Based on gene set enrichment analysis(GSEA)method,macrophage inflammation related pathways were screened,and normalized enrichment score(NES)was used to identify pathways that were reversed by traditional Chinese medicine treatment,revealing the interventional mechanism of Bufei Yishen formula and its compatibility.Results The NES of Bufei Yishen formula was-1377.23,among which the NES of Bushen compatibility was-485.07,that of Huoxue was-351.86,Huatan was-303.71,and Yiqi was-236.59.There were 213 significantly disturbed pathways reversed after the intervention of Bufei Yishen formula,among which there were 184 reversed pathways for Huoxue compatibility,147 reversed pathways for Bushen,134 reversed pathways for Huatan,133 reversed pathways for Yiqi,and the reversal rate was 75.41%,60.25%,54.92%,54.51%,respectively.90 pathways,including TGF-β production,were significantly reversed in the four compatibilities.Positive regulation of cytokine production involved in inflammatory response etc were specifically reversed pathways for compatibility.Conclusion The intensity of Bufei Yishen formula that reversed macrophage-inflammatory related pathways was in order of Bushen,Huoxue,Huatan and Yiqi compatibility.And the number of pathways that could be reversed by the compatibility of Bufei Yishen formula was Huoxue,Bushen,Huatan and Yiqi.Bufei Yishen formula could regulate the common and specific reversal pathways of the compatibilities to intervene the inflammatory response.

Objective:To explore the characteristic of dynamic function network connectivity (dFNC) of resting brain networks in internet gaming disorder (IGD) adolescents.Methods:Forty-four adolescent IGD subjects (IGD group, male/female: 38/6) and fifty healthy controls (HC group, male/female: 40/10) were collected, and the subjects completed demographic questionnaires, Young internet addiction scale(YIAS), Chinese adolescents' maladaptive cognitions scale(CAMAS), and functional magnetic resonance imaging (fMRI) tests. The fMRI data were preprocessed on the Matlab platform, and the preprocessed data was divided into 64 components for group level independent component analysis.The dynamic functional connectivity of obtained 18 effective independent components was analyzed by sliding time window technique, and the difference of dynamic functional connectivity of brain triple network between the IGD group and HC group was compared using SPSS 22.0 software.Results:Four repeated dFNC states were identified through cluster analysis.Each state indicated that different functional networks had different connection strengths.State 3, the most frequent state, had been indicated that the whole brain network of the subject was in a state of weak functional connectivity.The second frequent state was state 1, which indicated enhanced functional connectivity within the subject's central executive network (CEN).State 2 had been indicated enhanced functional connectivity within the subject's salience network (SN).State 4 had been indicated generally enhanced functional connectivity in the subjects' brain networks, and this state was the least frequent.The results of non-parametric permutation test on the time attribute showed that compared with the HC group, the IGD group had a longer time score (IGD group: 0.24±0.19, HC group: 0.13±0.15, t=1.19, P<0.05, non-parametric substitution test) for state 1 with strong connectivity within the CEN, which was positively correlated with the YIAS score and game time ( r=0.418, P=0.003; r=0.515, P=0.004).Compared with HC group, the functional connectivity of ICD group between the internal insula of the SN and the dorsal anterior cingulate cortex was enhanced ( P<0.05, FDR corrected), while the average residence time in weakly connected state 3 was longer ( Z=2.09, P<0.05, nonparametric substitution test). Conclusions:The difference in dynamic functional connectivity of the triple network in the brain of IGD adolescents under resting state is mainly manifested by strong connections in CEN, functional connections between insula and dorsal anterior cingulate cortex in SN is enhanced, and weakening of overall functional connections, which may play an important role in the pathological mechanism of IGD.

Objective:To explore the heterogeneity among keloids before and after radiotherapy and identify the changes of key cell subpopulations and their interactions utilizing single cell RNA sequencing technology.Methods:Four patients provided a total of 12 samples, each consisting of keloid tissue before and after radiotherapy and the normal skin tissue adjacent to the untreated keloid. The keloid was divided into left and right sides from the midline, and the left-side keloid was fractionally irradiated with 20 Gy electron beam in total in 4 consecutive days. The right-side keloid was irradiated with 10 Gy in 2 fractions before surgery and 10 Gy in 2 fractions after surgery.Results:A total of 25 573 fibroblasts were analyzed and categorized into nine subgroups (fibroblasts 1-9). The proportion of fibroblast-2 increased after radiotherapy ( t=4.70, P<0.05). The number of classical monocytes and macrophages increased after radiotherapy, but there was no significant difference due to the shorter time of sample taking at 2 d after radiotherapy ( P>0.05). Macrophages (4 723 cells) were further divided into four categories. CellPhoneDB analysis showed that type-3 macrophages interacted significantly more closely with fibroblasts than type-1 and type-2 macrophages. The most prominent signaling pathways for the interactions between type-3 macrophages and major fibroblast subtypes were the collagen signaling pathway and the chemerin signaling pathway. These interactions were more pronounced in the keloid samples after radiotherapy. Conclusions:The interactions between type-3 macrophages and fibroblasts (such as fibroblast-2) may serve as an important point for future studies on radio-sensitization of keloids.

Objective:To investigate the correlation of retinal blood vessel density with blood pressure and retinal thickness in the macular region of glaucoma.Methods:A retrospective study. From March 2019 to March 2022, 100 glaucoma patients of 100 eyes (glaucoma group) and 100 healthy people of 100 eyes (control group) diagnosed in Department of Ophthalmology of Luoyang First People's Hospital were included in the study. The patients in the glaucoma group were subdivided into the early, intermediate, and late groups based on the average visual field defect value, which were 38, 32, and 30 cases, respectively. Optical coherence tomography angiography was used to scan the macular area of the examined eyes in a 3 mm × 3 mm area. The software automatically divided the retina within 3 mm of the macular central concavity into 2 concentric circles centered on the macular central concavity, which were the central concave area with a diameter of 1 mm and the paracentral concave area with a diameter of 1-3 mm. The blood flow density and retinal thickness of the superficial retinal capillary plexus in the nasal, temporal, inferior, and superior quadrants of the retina within 3 mm of the macula were measured. Blood pressure was measured at the brachial artery using an electronic sphygmomanometer. Comparisons between two groups were made by independent samples t test, and comparisons between multiple groups were made by one-way analysis of variance. Correlations between retinal blood flow density and blood pressure and retinal thickness were analyzed by Spearman's correlation analysis. Results:The retinal blood vessel density in the central fovea, parafoveal, inferior, and superior macular areas in the glaucoma group were lower than that in the control group, and with the aggravation of the disease, the retinal blood vessel density in the central fovea, parafoveal, inferior and superior macular areas gradually decreased; the retinal thicknesses in the foveal, parafoveal, inferior, and superior macular areas in the glaucoma group were lower than those in the control group, and with the aggravation of the disease, the retinal thicknesses in the foveal, parafoveal, inferior, and superior macular areas gradually decreased, the differences were statistically significant ( P<0.05). Systolic and diastolic blood pressure were higher in the glaucoma group than in the control group, and they increased gradually as the disease worsened ( P<0.05). Spearman's correlation analyses showed that in glaucoma patients, the density of retinal blood vessels in the macular central plexus, paracentral plexus, and inferior and superior retinas was positively correlated with retinal thickness in the corresponding areas and negatively correlated with blood pressure ( P<0.05). Conclusion:The density of retinal blood vessels in the macular central plexus, paracentral plexus, and inferior and superior retinas are positively correlated with retinal thickness in the corresponding areas and negatively correlated with blood pressure.

AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groups:the control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model group:increased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P＜0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P＜0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P＜0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P＜0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.

Objective To exploring the mechanism of Jinshui Chenfei formula(JCF)in ameliorating silica(SiO2)-induced silicosis fibrosis based on endogenous metabolite changes.Methods A total of 32 SPF male Sprague-Dawley(SD)rats were divided into normal control group,model group,JCF group(9.72 g·kg-1·d-1),and Tetrandrine group(27 mg·kg-1·d-1)according to random number table method.The experimental silicosis model was established by intratracheal injection with SiO2 suspension(250 mg/kg)on day 1.From week 5-8,silicosis rats were treated with tetrandrine or JCF.On the end of week 8,the changes of pulmonary function index,including forced vital capacity(FVC),tidal volume(TV)and lung dynamic compliance(Cydn)were detected.The pathological changes of lung tissue were analyzed by hematoxyline-osin(HE)staining and Masson staining,the severity of focal alveolitis and fibrosis was also evaluated using the Szapiel scale and the Ashcroft scale,the positive staining of collagen Ⅰ(COL Ⅰ)and COL Ⅲ was detected using immunohistochemistry;the protein expression of transforming growth factor-β1(TGF-β1),fibronectin(FN),andα-smooth muscle actin(α-SMA)were measured by Western blotting.The rat serum samples were further screened for differential metabolites using ultra performance liquid chromatographytandem quadrupole time of flight mass spectrometr(UPLC-Q-TOF-MS)and pathway analysis was performed based on MetaboAnalyst 5.0.Results Compared with those in the normal control group,pathological changes such as alveolar structure destruction,the fibrous nodules encapsulated SiO2 particles were increased in lung tissues of rats in model group,alveolitis score and pulmonary fibrosis score were significantly higher(alveolitis score:2.62±0.27 vs.0.20±0.15,pulmonary fibrosis score:5.42±0.66 vs.0.50±0.84,both P<0.01);pulmonary function index including Cydn,FVC,and TV were significantly decreased[Cdyn(mL/cmH2O):0.26±0.03 vs.0.33±0.03,FVC(mL):8.09±0.47 vs.10.99±0.38,TV(mL):1.95±0.19 vs.2.53±0.26,all P<0.01];positive staining of COL Ⅰ,COL Ⅲ and ɑ-SMA,FN,TGF-β1 proteins expression showed higher in lung tissues[positive staining of COL Ⅰ(A value):13.47±1.76 vs.5.77±0.45;positive staining of COL Ⅲ(A value):10.39±0.47 vs.6.19±0.77,FN protein expression(FN/GAPDH):0.33±0.02 vs.0.21±0.07,α-SMA protein expression(α-SMA/GAPDH):1.78±0.16 vs.1.11±0.24,TGF-β1 protein expression(TGF-β1/GAPDH):0.52±0.10 vs.0.11±0.46,all P<0.01].Compared with the model group,the pathological changes of lung tissues were almost restored,alveolitis score and lung fibrosis score were significantly reduced in JCF and Tetrandrine groups(alveolitis score:1.10±0.15,1.33±0.31 vs.2.62±0.27,pulmonary fibrosis score:3.50±0.45,4.33±0.98 vs.5.42±0.66,all P<0.01);the pulmonary function index Cydn,FVC and TV were significantly increased[Cdyn(mL/cmH2O):0.32±0.05,0.31±0.04 vs.0.26±0.03,FVC(mL):9.41±0.85,8.70±0.92 vs.8.09±0.47,TV(mL):2.70±0.19,2.27±0.15 vs.1.95±0.19,all P<0.05];positive staining of COL Ⅰ,COL Ⅲ,and protein expression of FN,ɑ-SMA,and TGF-β1 in lung tissues was significantly decreased[COL Ⅰ(A value):7.09±0.67,8.13±0.64 vs.13.47±1.76,COL Ⅲ(A value):8.19±0.66,8.52±0.22 vs.10.39±0.47,FN protein expression(FN/GAPDH):0.19±0.06,0.24±0.03 vs.0.33±0.02,α-SMA protein expression(α-SMA/GAPDH):0.89±0.41,0.88±0.08 vs.1.78±0.16,TGF-β1 protein expression(TGF-β1/GAPDH):0.04±0.03,0.06±0.01 vs.0.52±0.10,all P<0.05].Metabolomics analysis showed that a total of 10 major differential metabolites were identified between normal control group,model group and JCF group,including arachidonic acid,palmitic acid,indole-3-acetic acid,propionylcarnitine,(S)-4-hydroxymandelonitrile,nalidixic acid,benzocaine,gramine,4-ethylphenol,N-benzylfor mamide.The differential metabolites in silicosis rats reversed by JCF treatment were mainly enriched,including unsaturated fatty acid biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.Conclusion JCF could effectively improve the silicosis fibrosis,which is mainly related to biosynthesis of unsaturated fatty acids biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.

BACKGROUND: Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. METHODS: This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. RESULTS: After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P  < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P  = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. CONCLUSIONS Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.
Adult ; Humans ; United States/epidemiology* ; Nitrates/adverse effects* ; Nutrition Surveys ; Thiocyanates/urine* ; Perchlorates/urine* ; Creatinine ; Environmental Exposure ; Renal Insufficiency, Chronic/epidemiology* ; Logistic Models

Objective:To improve the understanding of autoimmune lymphoproliferative syndrome (ALPS).Methods:The clinical data of the proband and his family members in Children's Hospital Affiliated to Zhengzhou University in August 2018 were retrospectively analyzed, and the peripheral blood DNA of the proband, his parents and siblings was extracted. High-throughput next-generation sequencing was used to make gene analysis and validation. Phenotype and genotype of them were also analyzed. Relevant literature was reviewed.Results:The proband was a 1-year and 1-month old boy with hemolytic anemia, thrombocytopenia and splenomegaly as the main manifestations. The double negative T cells and the Vitamin B 12 of the proband were significantly increased and the autoantibodies were positive. The boy's father had a history of splenomegaly. His elder brother and sister had similar clinical manifestations. The results of next-generation sequencing showed that the FAS gene frameshift mutation (c.648delT) was detected in this boy and his father, elder brother and sister, which was a new mutation. After immunosuppressive treatment, the symptoms of the boy improved and the blood cells increased. Conclusions:The frameshift mutation of FAS gene may be the cause of the disease in this ALPS pedigree. Clinically, it is necessary to consider ALPS for children with unexplained hemocytopenia and hepatosplenomegaly. Double-negative T cells, autoantibodies, Vitamin B 12 should be tested, and high-throughput gene sequencing should be performed if necessary.

Pneumoconiosis is an occupational lung disease with the highest incidence in China. There is no effective treatment drug at present. Animal and cell models are the basis for exploring its pathogenesis and developing effective drugs. In this paper, we sort out the methods of animal models of pneumoconiosis and the different cell models induced by dust in recent years, by analyzing and summarizing the advantages and disadvantages, modeling time, pathology and changes in important indicators of different preparation methods of animal models, as well as different cell models induced by the dust to simulate different pathological models and pathological stages, to provide basis for the application and improvement of pneumoconiosis model.

Pneumoconiosis is an occupational lung disease with the highest incidence in China. There is no effective treatment drug at present. Animal and cell models are the basis for exploring its pathogenesis and developing effective drugs. In this paper, we sort out the methods of animal models of pneumoconiosis and the different cell models induced by dust in recent years, by analyzing and summarizing the advantages and disadvantages, modeling time, pathology and changes in important indicators of different preparation methods of animal models, as well as different cell models induced by the dust to simulate different pathological models and pathological stages, to provide basis for the application and improvement of pneumoconiosis model.