Background Pneumoconiosis is the most serious occupational disease in China, and silicosis accounts for about half of it. Any intervention effect of physical exercise as the key and core of lung rehabilitation training on silicosis is still unclear. Objective To explore potential intervention effect of physical exercise on silicotic mice. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups, 10 in each group, including a control group, a physical exercise group, a silicosis model group, and a silicosis model + physical exercise intervention group. Silicotic mouse model was established by using 50 μL SiO₂ suspension (200 mg·mL⁻¹). A treadmill was used to prepare mice receiving physical exercise at 0° inclination, 12.3 m·min⁻¹, 60 min·d⁻¹, 5 d·week⁻¹ for 4 weeks. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after Van Gieson (VG) staining; expression of p-protein kinase R-like endoplasmic reticulum kinase (PERK) was detected by immunofluorescence staining; expressions of cyclin dependent kinase inhibitors (p21) and p-p38 mitogen activated protein kinase (p38) were detected by immunohistochemistry. The protein expressions of endoplasmic reticulum stress signal factors [p-inositol-requiring enzyme-1α (p-IRE-1α), p-PERK, and p-eukaryotic initiation factor-2α (p-eIF-2α)], senescence signal factors (p-p53, p21, and p16), mitogen-activated protein kinase (MAPK) signal factors [p-p38, p-extracellular regulated protein kinases (p-ERK), and p-stress-activated protein kinase (p-JNK)] were detected by Western blotting. Results After designed acute SiO₂ exposure, the images of micro computed tomography (CT) showed high density shadows in lung tissues of the silicotic mice and less shadows in lung tissues of the physical exercise intervention mice. After HE staining, the proportions of silicotic nodule area in lung tissues was (18.67±3.89) % in the silicosis model group, and significantly decreased to (8.78±1.05) % in the silicosis model + physical exercise intervention group (P<0.05). After VG staining, the proportion of collagen fiber area of lung tissues was (10.37±2.18) % in the silicosis model group, and significantly decreased to (4.35±0.89) % in the silicosis model + physical exercise intervention group (P<0.05). The results of immunofluorescence staining showed that in the silicosis model group, the expression of p-PERK increased at the location of silicotic nodules, while in the silicotic model + physical exercise intervention group, the expression of p-PERK decreased. The immunohistochemical staining results showed that the expression of p21 and p-p38 increased in the lung tissues of the silicosis model group; the expression of p21 and p-p38 decreased in the lung tissues of the silicosis model + physical exercise intervention group. The results of Western blotting showed that compared with the control group, the expression levels of p-IRE-1α (0.11±0.03), p-PERK (0.95±0.40), p-eIF-2α (3.53±0.91), p-p53 (1.78±0.07), p21 (1.98±0.10), p16 (1.26±0.17), p-p38 (0.41±0.09), p-ERK (0.42±0.05), and p-JNK (3.20±1.23) of the silicosis model group were all upregulated (P<0.05). Compared with the silicosis model group, the expression levels of p-IRE-1α (0.03±0.01), p-PERK (0.31±0.12), p-eIF-2α (0.30±0.06), p-p53 (0.76±0.08), p21 (0.18±0.11), p16 (0.70±0.24), p-p38 (0.03±0.00), p-ERK (0.19±0.03), and p-JNK (0.46±0.21) of the silicosis model + physical exercise intervention group were downregulated (P<0.05). Conclusion Physical exercise may alleviate pulmonary fibrosis in silicotic mice, and inhibit abnormal expressions of endoplasmic reticulum stress signal, MAPK signal, and senescent signal.

Objective: To investigate the expression of lysophosphatidic acid(LPA) in mouse silicosis model and its effect on epithelial-mesenchymal transition(EMT) of mouse lung epithelial(MLE-12) cells. Methods: 20 C57 BL/6 male mice were randomly divided into the control group and the model group. The control group was given normal saline, and the model group was given nasal drip of 50 μl silicon dioxide(SiO2) suspension with 100 mg/L every day for 7 consecutive days. They were killed on the 28 th day. Partial lung tissues were taken. Immunohistochemistry was used to observe the expression of lysophosphatidic acid receptor 1(LPAR1), and Western blot was used to detect the protein expression of α-smooth muscle actin(α-SMA),Type Ⅰ collagen( COLⅠ) and LPAR1; the proliferation of MLE-12 was detected by solution cell proliferation assay; scratch test was used to detect the migration ability of SiO2on MLB-12 cells. MLE-12 cells were divided into control group, SiO2stimulation group and inhibitor group, and the expression levels of LPARI and EMT related proteins were detected by Western blot. Results: Western blot detection showed that the expression of α-SMA and COLⅠin the lung tissue of mice from the model group increased, and the model was established successfully; immunohistochemistry showed that the expression of LPAR1 was positive in the epithelial cells around the trachea and bronchus of the model group mice, showing bright brown; Western blot detection found that the expression of LPAR1 protein in the lung tissue of mice from the model group was higher than that from the control group(P<0.05); cell proliferation assay and scratch test showed that SiO2could significantly promote the proliferation and migration of MLE-12 cells; Western blot showed that the expression of LPAR1 and interstitial marker Vimentin protein increased in SiO2stimulation group(P<0.05), while the expression of epithelial marker E-cadherin protein decreased(P<0.05), and the difference was statistically significant compared with the control group and the inhibitor group(P<0.05). Conclusion The expression of LPA increased in mouse silicosis model, which can promote the proliferation and migration of MLE-12 cells by regulating EMT process and exacerbates the process of silicosis in mice.

Objective : To investigate the effect of glycyrrhizin on the fibrosis of silica⁃treated mice. Methods : C57BL/6 male mice were randomly divided into control group , silicosis model group and glycyrrhizin treatment group ,with 6 mice in each group. The pathological changes of lung tissues were observed by HE and Sirius red stai⁃ ning. Lung function indexes were detected by respiratory function instrument. The content of hydroxyproline in the lung tissues was detected by corresponding kit. The mRNA levels of monocyte chemotactic protein 1 (MCP⁃1) , fibronectin (FN) and alpha⁃smooth muscle actin ( α ⁃SMΑ) were detected by real⁃time fluorescent quantitative PCR. The number of leukocytes in the bronchoalveolar lavage fluid (BALF) was counted and the secretion of transforming growth factor⁃β1 (TGF⁃ β1) in BALF was detected by ELISA. Results : HE and Sirius red staining showed that the inflammatory cells and the collagen were accumulated in the lung tissue of mice in silicosis model group. After treatment with glycyrrhizin , the accumulation of inflammatory cells and the collagen was ameliorated. Compared with the control group , pause (PAU) and enhanced pause (Penh) increased in the model group (P < 0. 05) . Glycyrrhizin treatment improved the respiratory function in mice. Furthermore , glycyrrhizin also effectively reduced the increase in the content of hydroxyproline , the expression of MCP⁃1 , FN and α ⁃SMΑ mRNA , the number of leukocytes and the secretion of TGF⁃ β1 induced by silica treatment in mice (P < 0. 05) . Conclusion Glycyrrhizin can improve the pulmonary function and alleviate the fibrosis in mice with silicosis.

OBJECTIVE: To investigate the effect of liver X receptor(LXR)-adenosine triphosphate-binding cassette transporter A1(ABCA1) signaling pathway on the free silica(SiO_2)-induced foaming of macrophages. METHODS: Human histiocytic lymphoma U937 cells were induced to differentiate into macrophages by phorbol myristate acetate. The macrophages at logarithmic growth phase were randomly divided into 4 groups: the cells in the control group received no treatment, the cells in the SiO_2 stimulation group were stimulated with SiO_2 suspension at a dose of 50 mg/L, and the cells in the oxidized low-density lipoprotein(ox-LDL) group were treated with ox-LDL at the dosed 50 mg/L, the cells in the combination group were simultaneously stimulated with SiO_2 suspension and ox-LDL at a dose of 50 mg/L. Cells were collected after 48 hours of culture. Macrophage foaming was observed by oil red O staining. The levels of total cholesterol(TC), free cholesterol(FC), cholesteryl ester(CE) and CE specific gravity(CE%) in macrophages were detected using a microplate reader. The expression of LXR and ABCA1 was detected using Western blotting. RESULTS: The results of the oil red O staining showed that all the macrophages in the SiO_2 stimulation group, ox-LDL group and the combination group had foaming changes. The degree of foaming in the macrophages in the combination group was higher than that in the other two groups. The levels of TC, FC, CE and CE% in macrophages increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), in SiO_2 stimulation group, ox-LDL group and combination group compared with the control group. The macrophages in the combination group were transformed into foam cells. The levels of TC, FC, CE and CE% in macrophages of the combination group increased(P<0.05), and the protein relative expression of LXR and ABCA1 decreased(P<0.05), compared with the SiO_2 stimulation group and the ox-LDL group. CONCLUSION:sFree SiO_2 can induce foaming of macrophages, and ox-LDL in combination with SiO_2 has a synergistic effect on the formation of foaming of macrophages.The process of macrophage foaming may be achieved by inhibiting the LXR-ABCA1 signaling pathway.

OBJECTIVE: To investigate the preventive effect of rock salt aerosol on the development of silicosis in rats. METHODS: The specific pathogen free adult male SD rats were randomly divided into normal control group, rock salt control group, silicosis model group and rock salt intervention group, 18 rats in each group. Rats in the silicosis model group and the salt rock intervention group were treated with silica dust at the concentration of 2 000.0 mg/m~3 by dynamic dusting method for 3 hours daily. Rats in the rock salt control group and the rock salt intervention group inhaled the rock salt aerosols with the mass concentration of 20.0 mg/m~3 for 30 minutes daily. The normal control group was not treated with the dust or rock salt aerosol. At the time points of 14, 28 and 56 days after exposure to dust or rock salt aerosol, 6 rats were randomly selected from each group and samples were collected. The pathological change of lung was observed, the total cell count in the bronchoalveolar lavage fluid(BALF) was performed, the enzyme-linked immunosorbent assay was used to detect the change of transforming growth factor-β(TGF-β) in BALF, surfactant D(SP-D) and superoxide dismutase(SOD) in lung tissue. RESULTS: The results of hematoxylin-eosin and Masson staining showed that the inflammatory changes of lung tissue and the pulmonary interstitial fibrosis in the rock salt intervention group were less severer than that in the silicosis model group. At 14, 28, and 56 days after dust exposure, the total cell counts in BALF and SP-D levels in lung tissue of rats in silicosis model group and rock salt intervention group were higher(P<0.05), the SOD activities in lung tissue were lower(P<0.05), as well as the TGF-β levels in BALF in silicosis model group were higher(P<0.05),compared with the normal control group and rock salt control group. The total cell counts and TGF-β levels in BALF, and SP-D levels in lung tissue of rock salt intervention group were lower(P<0.05), the SOD activities in lung tissue were higher(P<0.05), compared with the silicosis model group. CONCLUSION: Rock salt aerosol intervention may delay the pathogenesis of silicosis by improving the inflammatory response, regulating oxidative stress and reducing interstitial fibrosis of lungs.

Objective:To investigate the safety and efficacy of tirofiban therapy in acute cerebral infarction patients having broadened therapeutic time window.Methods:Eighty-four acute cerebral infarction patients having broadened therapeutic time window (the onset time was within 4.5-8 h), admitted to our hospital from January 2016 to May 2018, were chosen in our study. Forty-two patients (treatment group), with the informed consent of himself or his family, received emergent cerebral angiography and treated with tirofiban (the load of tirofiban was pumped via the microductal artery, and the maintenance load was continuously pumped intravenously for 48 h) right after the angiography; the other 42 patients (control group) received emergent cerebral angiography and treated with intensive antiplatelet aggregation therapy right after the angiography; intensive lipid-lowering therapy was given in both groups. The efficacy, safety and follow-up rehabilitation were compared between the two groups. According to the locations of acute cerebral infarction, patients in the treatment group were divided into anterior circulation infarction subgroup ( n=24) and posterior circulation infarction subgroup ( n=18); the efficacy and follow-up rehabilitation were compared between the two subgroups. Results:Patients from the treatment group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores 48 h, 7 d, and 10 d after treatment, and significantly higher NIHSS score difference values before and after treatment than those from control group ( P<0.05); the proportion of patents having good prognosis (modified Rankin scale [mRS] scores≤2) in the treatment group 3 months after treatment (78.57%) was significantly higher than that in the control group (52.38%), and the Barthel index in the treatment group 3 months after treatment (94.76±11.67) was significantly higher than that in the control group (85.00±15.17, P<0.05). Patients from the posterior circulation infarction subgroup had significantly lower NIHSS scores 48 h, 7 d, and 10 d after treatment, and significantly higher NIHSS score difference values before and after treatment than those from anterior circulation infarction subgroup ( P<0.05); the proportion of patents having good prognosis in the posterior circulation infarction subgroup 3 months after treatment (94.44%) was significantly higher than that in the anterior circulation infarction subgroup (66.67%, P< 0.05). There were no statistically significant differences in platelet count and coagulation tests between the treatment group and control group, and between the posterior circulation infarction subgroup and anterior circulation infarction subgroup ( P>0.05). Conclusion:Tirofiban could improve the prognoses of patients with acute cerebral infarction in broadened therapeutic time window, enjoying high effectiveness and safety, which are more obvious in the posterior circulation infarction.

Objective To compare the clinical features and prognosis between dermatomyositis-associated interstitial lung disease (DM-ILD) and idiopathic pulmonary fibrosis (IPF).Methods Patients with interstitial lung disease with dermatomyositis (DM-ILD) or idiopathic pneumonia fibrosis (IPF) from January 2003 to March 2014 in the third affiliated hospital of Sun Yat-sen University were included.Results Among the 64 patients enrolled,44 were DM-ILD and 20 were IPF.IPF was more common in the elderly (P =0.000),men (P =0.004) and smokers (P =0.000),and its high-resolution computed tomography (CT) mostly showed grid shadow (P=0.014) and honeycomb shadow (P=0.000).DM-ILD usually had cough symptoms (P =0.025).High-resolution CT showed patchy (P =0.048) and banded (P =0.000).Glucocorticoid (P =0.000) and immunosuppressive agents (P =0.000) were commonly used in the treatment of DM-ILD.However,there was no significant difference in 90d mortality between the two groups (P ＞ 0.05).Conclusions IPF is more common in the elderly,men and smokers,and its high-resolution CT mostly shows grid shadow and honeycomb shadow,distribution is diffuse.DM-ILD often has cough symptoms,and its high resolution CT is mostly plaques and streaky shadows.Glucocorticoids and immunesuppressants are commonly used in DM-ILD,but there is no significant difference in 90-day mortality between them.

Objective To investigate the feasibility,effectiveness,and technical superiority of Solumbra thrombectomy for treatment of acute large cerebral artery occlusion stroke.Methods 32 patients who had acute large cerebral artery occlusion stroke and received mechanical thrombectomy in TEDA Hospital of Tianjin between January 2013 and August 2016,were divided into two groups:stent group(with conventional stent-retrievers,n=21) and Solumbra group (with Solumbra thrombectomy,n =11).Clinical characteristics,variables correlated with operation,and clinical outcomes were compared and analyzed retrospectively.Results There were no differences in basic clinical and radiographic parameters between stent group versus Solumbra group (all P＞0.05).Moreover,there were no differences between Solumbra group versus Stent group in rates of embolus to new territory(18.2 ％ vs.28.6％,P=0.425),in times of thrombectomy(2.2± 1.0 vs.2.4± 1.3,P=0.657),in nonsymptomatic intracranial hemorrhage (18.2％ vs.14.3％,P =0.572),in symptomatic intracranial hemorrhage(18.2％ vs.9.5％,P =0.427),in TICI 2b/3 revascularization(81.8％ vs.81.0％,P =0.670),in puncture-to-reperfusion time[(66.4±39.0)min vs.(51.6±34.5)min,P=0.279],and in NIHSS at 7 days(11.6 ± 7.7 vs.11.3 ± 7.2,P =0.925).A modified Rankin Scale(mRS ≤2) is a variable of recovery of function and good clinical outcome at 90 days.The levels of mRS were similar(P =0.490)between Solumbra and stent groups,but there was a tendency to higher rate of good clinical outcome at 90 days in Solumbra group (63.6％,7/11)than in stent group (47.6％,10/21).Conclusions Solumbra thrombectomy as intravascular revascularization technique is an effective and safe strategy for endovascular recanalization of acute large cerebral artery occlusion stroke.Compared with conventional Stent-Retriever thrombectomy,Solumbra thrombectomy has a good clinical outcome tendency at 90 days after operation.

Objective To analyze the rules of acupoint selection in treating knee osteoarthritis with acupuncture and moxibustion therapy based on data mining; To provide references for clinical treatment.MethodsArticles about treating knee osteoarthritis with acupuncture and moxibustion were retrived from China National Knowledge Infrastructure (CNKI), Wanfang academic periodical full-text database, Chinese Journal Full-text Database (VIP) and SinoMed in China from Jan. 1st 2006 to Jan. 1st 2016. The database of acupuncture and moxibustion prescription was set up. The Apriori association rules, system cluster analysis and factor analysis were adopted in order to analyze the rules of acupoint selection for knee osteoarthritis.ResultsTotally 190 articles were included, covering 228 acupuncture- moxibustion prescriptions, 65 acupoints and the total frequency for 1736 times. The usual acupoints in the lower limbs were Dubi (ST35), Neixiyan (EX-LE 4), and Yanglingquan (GB34). The main maridians were Stomach Meridian of Foot-Yangming, Spleen Meridian of Foot-Taiyin, and Gallbladder Meridian of Foot-Shaoyang, accounting to for 1626 times (93.66%). Cluster analysis achieved other four groups of acupoint selection based on syndrome differentiation.ConclusionLocal acupoints and dialectical point selection were important principle in treating knee osteoarthritis combined with acupoint selection based on syndrome differentiation.

Objective To investigate the feasibility, safety and technical superiority of mechanical thrombectomy using a direct aspiration first-pass thrombectomy (ADAPT) in treatment of patients with acute cerebral artery occlusion. Methods A retrospective study was conducted on all patients with acute ischemic stroke treated with mechanical thrombectomy in our institution from January 2013 to August 2016.Patients using ADAPT or stent retriever as a first-line endovascular procedure were compared for clinical characteristics, procedural variables and clinical outcomes. The technical superiority of ADAPT was analyzed in depth. Results During observation period, a total of 91 cases were performed endovascular treatment with mechanical thrombectomy. ADAPT was designed in 46 cases as a first-line endovascular procedure and was utilized in 38 cases (82.6%;ADAPT group), while primary stent retriever thrombectomy was performed in 21 patients(stent group). There was no significant difference in baseline clinical or radiographic factors between ADAPT and stent groups. Although rates of good neurological outcome (modified Rankin Scale(mRS) score≤2) at 90 days were similar between the ADAPT and stent groups (61%(23/38) vs 48%(10/21), P=0.247), National Institute of Health Stroke Scale (NIHSS) score at seven days (6.0(2.0, 9.3) vs 9.0(5.5, 18.5),Z=-2.031,P=0.021) and full recovery rate of neurological outcome (mRS score=0, 37%(14/38) vs 10%(2/21), P=0.022) were significantly better in the ADAPT group than in the stent group. There were no significant differences in rates of embolus to new territory (21%(8/38) vs 29%(6/21), P=0.365), Thrombolysis In Cerebral Infarction (TICI) 2b/3 grade revascularization (84%(32/38) vs 81%(17/21), P=0.507) and symptomatic intracerebral hemorrhage (0%(0/38) vs 10%(2/21), P=0.123) between the ADAPT and the stent groups, but the figures were better in the ADAPT group. Conclusions Mechanical thrombectomy using ADAPT is feasible and safe compared with stent retriever, with higher full recovery rate of neurological outcome and better NIHSS score.It is a method worthy of further exploration for endovascular mechanical recanalization.