Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

Objective:To investigate the role of the Smad3 signaling pathway in the process of silica-induced epithelial-mesenchymal transition (EMT) .Methods:In September 2022, lung epithelial cells (BEAS-2B) were exposed to different concentrations of silica suspension (0, 50, 100, and 150 μg/ml) for 6 and 12 hours. Additionally, SIS3, a specific inhibitor of phosphorylated Smad3 (p-Smad3) , was utilized to establish the p-Smad3 inhibition model. The cells were divided into four groups: blank control gruop, silica group, SIS3 intervention group, and SIS3 +silica group. Cell morphology was observed using an inverted fluorescence microscope, while cell viability was assessed using a Cell Counting Kit-8 (CCK-8) . The mRNA and protein expression levels of E-cadherin (E-Cad) , N-cadherin (N-Cad) , Vimentin, Smad3, and p-Smad3 were analyzed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Differences between two groups were compared using Student's t-test, and multiple group comparisons were analyzed using a one-way analysis of variance with the Student-Newman-Keuls test.Results:Compared with the blank control group, the morphology of BEAS-2B cells shifted from epithelial to mesenchymal cell-like following silica exposure, and the cell viability of BEAS-2B cells declined after exposure to 150 μg/ml silica for 6 and 12 hours. Furthermore, silica exposure led to significant reductions in mRNA and protein expression levels of the epithelial cellular marker (E-Cad) in BEAS-2B cells, accompanied by increased expressions of interstitial cellular markers (N-Cad and Vimentin) . Importantly, the level of p-Smad3/Smad3 expression levels was also elevated in silica-treated cells ( P<0.05) . Compared to the blank control group, the level of p-Smad3/Smad3 expression levels was significantty reduced. Moreover, compared to the silica group, the protein expression levels of N-Cad and Vimentin in the cell of the SIS3+silica group were significantly reduced, while the E-Cad expression was increased ( P<0.05) . Conclusion:Silica exposure can prmote the epithelial mesenchymaol transformotion process by activating smod3 signa ling pathuay, and in hibiting smad3 signa ling pathuay can effctively alleviate the occurrence of epithelial mesenchymal transformation process.

Objective To detect the expressions of intercellular adhesion molecule-1(ICAM-1)and nu-clear factor(NF)-κB in hepatic tissues of the patients with chronic hepatitis B,and to analyze their correlation with the hepatic inflammatory activity and fibrosis degree.Methods The liver biopsy specimens from 66 pa-tients with hepatitis B and 10 non-hepatopathic controls were selected,and immunohistochemistry and in situ hybridization were used to detect ICAM-1 and NF-κB expression levels in different liver tissues.Results The positive rate of ICAM-1 and NF-κB expression in liver tissues of the patients with chronic hepatitis B was higher than that in normal liver tissues,and the difference was statistically significant(P＜0.05).The expres-sion of ICAM-1 and NF-κB in the patients with hepatitis B was positively correlated with the inflammatory ac-tivity and fibrosis degree(r=0.493,0.496,P＜0.01;r=0.580,0.519,P＜0.01).Conclusion ICAM-1 and NF-κB in the patients with chronic hepatitis B are highly expressed,which is useful in judging the hepatic in-flammatory activity and fibrosis degree.

OBJECTIVE To study the effects of Dianxianqing granules on the tau protein in P301S mice by regulating mitophagy. METHODS Totally 36 P301S mice were randomly divided into model group， Dianxianqing granule group （12.48 g/kg）， donepezil hydrochloride group （positive control， 1.3 mg/kg）， with 12 mice in each group； another 10 C57BL6 mice were selected as control group. Administration groups were given relevant drug solutions intragastrically， and control group and model group were given constant volume of water intragastrically. The gavage volume was 20 mL/kg， once a day， for consecutive 5 months. During the experiment， the general condition of mice was observed in each group. After the last medication， the learning and memory ability was determined by Y maze test and Morris water maze test； HE staining was used to observe the morphological changes in brain tissue， and Nissl staining was used to observe the structure of neural cells and the number of Nissl bodies in cerebral tissue. Immunohistochemistry was used to detect the expressions of phospho-tau serine 202/threonine 205 （abbreviated as AT8） in brain tissue. Western blot assay was used to determine the expressions of mitophagy-associated proteins [PTEN-induced putative kinase-1 （PINK1）， Parkin， microtubule-associated protein 1 light chain 3B （LC3B）， p62]， synaptic-associated proteins [postsynaptic density protein-95 （PSD-95）， synaptophysin （SYP）， and growth-associated protein-43 （GAP-43）] and the phosphorylation of tau protein [expressed by the phosphorylation levels of serine 199 （Ser199） and Ser202] in brain tissue. RESULTS The mice in E-mail：lnzyxyqy2003@163.com model group showed symptoms such as white hair， decreased body mass， and lower limb paralysis， with incomplete hippocampal structures in their brain tissue， as well as incomplete cell membrane edges and cell structures； the spontaneous alternating response rate， the times of crossing platform， the number of Nissl bodies， the protein expressions of PINK1， Parkin， LC3B， SYP， GAP-43， and PSD-95 were decreased significantly， compared with control group； swimming latency （fourth and fifth day）， the protein expressions of AT8 and p62，the phosphorylation levels of Ser199 and Ser202 were increased or lengthened significantly， compared with control group （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms and indexes of mice were improved significantly in administration groups （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granules can effectively improve cognitive impairment in P301S mice，the mechanism of which may be associated with inducing mitochondrial autophagy， reducing the hyperphosphorylation of tau protein， up-regulating the expression of synaptic-associated proteins in brain tissue，and repairing damaged neural cells.

Objective To study the proteomic profiling of lung and colon during lung injury induced by lipopolysaccharide(LPS).Methods Mice were divided into four groups:the control,LPS,LPS+ Platycodonis Radix(PR)and LPS+ Rhei Radix et Rhizoma(RRR).LPS was injected into the lungs through trachea,and the drugs were given by intragastric injection.The mice were weighed,the faeces of each mouse were determined,and the lungs and colon were isolated for analysis of pathophysiological changes and proteomics.Results ①After 7 days of LPS,the weight of mice decreased,the lung showed inflammatory changes,and the faeces increased.Both PR and RRR can improve the inflammation.②There are lot of proteins was increased in lung mainly involved in gene transcription and in colon mainly involved in mitochondrial,endoplasmic reticulum and metabolism,etc.The up-regulated proteins shared by both lung and colon were involved in myoprotein contraction.PR can inhibit the up-regulated protein more than RRR in lung.③There are large number of proteins were down-regulated in lung involved in cell membrane and in colon involved in nucleic acid binding and ATP binding.The down-regulated proteins shared by both lung and colon were involved in endoplasmic reticulum,nucleic acid binding and cell membrane,etc.The down-regulated proteins in lung by PR are more than those by RRR,which is involved in endoplasmic reticulum,cell membrane,etc.Conclusion LPS-induced lung injury can cause changes in the expression of protein in lung and colon proteins,and the increase in the expression of myoprotein contraction genes may be one of the molecular mechanisms related to lung and colon.

Objective To investigate the effects of 2, 2, 6, 6-tetramethyl-4-piperidinol (tempol) on NF-κB signaling pathway of myocardial hypertrophy in rats. Methods The rat model of myocardial hypertrophy was established by intraperitoneal injection of isoprenaline (ISO) (5 mg/kg, twice per day, 2 weeks). A total of 42 male SD rats were randomly divided into 3 groups, including the control group, myocardial hypertrophy model group (ISO + sterile saline) and tempol treatment group (ISO + tempol) [tempol 100 mg/ (kg·d), 8 weeks]. Eight weeks after the corresponding drug intervention, the heart weight index (HWI) and left ventricular weight index (LVWI) were determined. Morphology and fibrosis of the myocardium were observed by HE staining, and the myocardial fibrosis of the rats was observed by Masson staining. The mRNA levels of TNF-α and IL-6 in the rat myocardial tissues were detected by qRT-PCR, and the expression levels of IκBα, p-p65 and p65 were detected by Western blot. Results Compared with the control group, the HWI and LVMI, mRNA levels of TNF-α and IL-6, and expression of p-p65/p65 in the model group were significantly increased (P＜ 0. 05), while the expression level of IκBα, an NF-κB inhibitory protein was significantly decreased (P＜0. 05). The pathological examination of the myocardial tissues showed thickening and disordered arrangement of myocardial fibers, and increased cross-sectional area of the myocardial fibers. The pathology by Masson staining showed aggravated myocardial fibrosis and increased collagen fibers in the myocardial interstitium. Compared with the model group, the HWI and LVMI, the mRNA levels of TNF-α and IL-6, and the expression of p- p65/p65 of the tempol group were significantly decreased (P＜ 0. 05), while the expression level of IκBα was significantly increased (P＜ 0. 05). HE staining showed that the degrees of myocardial disarrangement and cardiomyocyte hypertrophy were decreased. Meanwhile, Masson staining showed that the extent of myocardial fibrosis was reduced, and the interstitial collagen fibers were decreased. Conclusions Tempol can improve the isoprenaline-induced myocardial hypertrophy, which may be closely related with the inhibition of the activity of NF-κB signaling pathway.

Objective To study the effects and mechanism of immediate application of transformation growth factor beta 1 (TGF-β1) neutralizing antibody postoperatively to prevent the fibrous capsule formation in animal model,and to observe the different effects between two concentrations of TGF-β1 neutralizing antibody.Methods Ten ml of smooth round silicone prostheses were implanted subcutaneously in the back of rats.Then 25 μg/0.1 ml or 50 μg/0.1 ml TGF-β1 neutralizing antibody were injected around the implanted prostheses in the experimental group,while the control group was injected with PBS 0.1 ml.On day 7,14 and 28,the thickness of capsule measured;The density of collagen;and the expression of TGF-β1,alpha smooth muscle actin (α-SMA),and fibronectin (FN) was detected.Results After 28 days,the average capsule thickness of the control group was significantly higher in the experimental group,and the difference between the control group and the 25 μg experimental group had statistical significance.TGF-β1 expression and the number of α-SMA positive fibroblasts in control group were significantly higher than that in the experimental group,the difference was statistically significant.In the control group,the expression of FN and collagen density was slightly higher than the two experimental groups,but the differences among the three groups showed no statistical significance at each time point.Conclusions Immediate application of the TGF beta 1 neutralizing antibody in the the implant prosthesis can reduce the thickness of the capsule to some extent.

Berberine (BBR) is known as a classic drug for intestinal infection treatment.BBR inhibits intestinal bacteria,which is the core of its role in the treatment of intestinal infection.With the survival of local intestinal bacteria and its related metabolites on the physiological and pathological functions of the body continue to recognize the impact of it,more and more literatures have presented the effect of BBR through the impact of intestinal bacteria on the body glycol-lipid metabolism,even brain function.This allows us to re-understand the pathophysiology of BBR in inhibiting gut microbiome.In this paper,the antibacterial activity of BBR was reviewed and analyzed.The possible molecular target of BBR was analyzed according to the characteristics of prokaryotes gene expression,which was helpful to the in-depth study of BBR on intestinal bacteria.Thus,a more comprehensive understanding of the pharmacological effects of BBR is given.

This article was aimed to study the quality control of pineapple leaf in order to further develop the appli-cations of pineapple leave as medicinal resources. The tissue structure of pineapple leaf was observed by tissue biop-sy assay. Thin-layer chromatography (TLC) was employed on the qualitative identification of ananasate in the leave. The p-coumaric acid and ananasate were detected with high-performance liquid chromatography (HPLC) assay in the content determination. The results showed that pineapple leaf can be divided into the upper and lower leaf epidermis with stoma under microscope observation. Ananasate of the leave can be indentified clearly by TLC. HPLC method can accurately detect the content of p-coumaric acid and ananasate of pineapple leave. There are different contents of p-coumaric acid and ananasate of pineapple leave in different origins. In Y unnan province, the contents of p-coumaric acid and ananasate of pineapple leave are the highest; while the contents of p-coumaric acid and ananasate in Guangxi province are the lowest. It was concluded that ananasate can be used in the quality identification. The p-coumaric acid and ananasate can be used in the quantitative determination in the better control of the quality of pineapple leaf.

OBJECTIVE:To investigate the feasibility,safety and efficacy of domestic small waist big edge-type occluder for patients with multiple outlets sac-type membranous ventricular septal defection (VSD),and summarize its technical problems and the choice of treatment strategies.METHODS:A total of 20 patients with sac-type membranous VSD,underwent left ventricular angiography at left anterior oblique 45°-60° plus CAOD 20°-25°;the left ventricular entrance diameters were 7-21 (10.9±5.2) mm,more than 2 outlets in the right ventricular surfaces,and the largest outlet diameters were 3-10 (4.8±2.9) mm.According to the result from transthoracic echocardiography (TTE) and angiography,the sac-bag size,shape,location,extent of tissue adhesion,and stability were determined.Different types of small waist big edge-type occluder were implanted,and the occluder diameter was 5-14 (4.6±2.8) mm.Following 15 minutes of blocking,the immediate effects of occlusion were observed through repeating left ventricuiar angiography and TTE.All patients rechecked ultrasonic cardiography and electrocardiogram at 5-7 days of hospital stay,and 1,3,6 and 12 months following surgery.All patients took aspirin tablets for 6 months.RESULTS:Of 20 patients,17 cases underwent domestic small waist big edge occluder,blocked successfully through left ventricular entrance,2 cases were successful using symmetry block,and 1 case was failed.Intraoperative occlusion did not affect the aortic valve and tricuspid valve function.There were 1 case with left bundle branch block and 1 case with right bundle branch block during the operation,and all recovered within a week by using hormone therapy.After 6 months,the cardiac sizes were reduced to different degrees.CONCLUSION:It is safe and effective to treat multiple outlets sac-shaped membranous VSD with domestic small waist big edge-type occluder.The key technology,according to the sac size,shape,firmness,outlet orientation,import size,and the size of aortic stump,is to determine the block site and to select a suitable occluder.