Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Recent advances in vital pulp therapy(VPT)research,coupled with the widespread use of biomaterials,have led to an in-crease in the application of VPT.The indications for VPT are continually expanding,particularly for fully developed permanent teeth.Currently,one-way membrane decompression is being investigated as a possible treatment to preserve vital pulp in cases of irreversible pulpitis.This technology involves creating an access point in the pulp cavity and using the one-way membrane to prevent microorganisms from invading the pulp tissue.Additionally,it helps alleviate the high pressure in the pulp cavity caused by inflammation,thereby en-hancing blood circulation within the pulp.This improvement is crucial for establishing a foundation for future vital pulp preservation treatments.A case of irreversible pulpitis caused by caries was reported,in which the dental pulp was preserved using the one-way membrane decompression.The results of a ten-month clinical follow-up indicate a positive outcome.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

Recent advances in vital pulp therapy(VPT)research,coupled with the widespread use of biomaterials,have led to an in-crease in the application of VPT.The indications for VPT are continually expanding,particularly for fully developed permanent teeth.Currently,one-way membrane decompression is being investigated as a possible treatment to preserve vital pulp in cases of irreversible pulpitis.This technology involves creating an access point in the pulp cavity and using the one-way membrane to prevent microorganisms from invading the pulp tissue.Additionally,it helps alleviate the high pressure in the pulp cavity caused by inflammation,thereby en-hancing blood circulation within the pulp.This improvement is crucial for establishing a foundation for future vital pulp preservation treatments.A case of irreversible pulpitis caused by caries was reported,in which the dental pulp was preserved using the one-way membrane decompression.The results of a ten-month clinical follow-up indicate a positive outcome.

OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Child ; Humans ; Case-Control Studies ; East Asian People ; Genetic Predisposition to Disease/genetics* ; Methyltransferases/genetics* ; Polymorphism, Genetic ; Wilms Tumor/pathology*