1.Effects of Long-term Aerosol Inhalation of 4 Kinds of Non-aerosol Drugs to Lung Tissue of Healthy SD Rats
Rongguo TANG ; Qian HE ; Lei FU ; Changye XU ; Xiujuan WANG ; Xiong LI ; Weilin OU
China Pharmacy 2019;30(9):1214-1219
		                        		
		                        			
		                        			OBJECTIVE: To study lung tissue injury induced by long-term aerosol inhalation of 4 kinds of non-aerosol drugs in healthy SD rats, and to evaluate the safety of aerosol inhalation of non-aerosol drugs. METHODS: Totally 40 healthy SD rats (♂) were randomly divided into 8 group, i.e. blank control group, normal saline group (solvent control), budesonide group (non-aerosol drug control, 0.1 g/L) ,silicon dioxide group (lung injury drug control, 40 g/L)and 4 kinds of non-aerosol drugs [Dingchuan decoction group (15 g/mL, calculated by crude drug), cefatriaxone group (200 g/L), Qingkailing group (stoste) and Tangreqing group (stoste)], with 5 rats in each group. Except that blank control group didn’t received any treatment, other groups received aerosol inhalation, 10 mL, twice a day, for consecutive 56 days. After medication, the number of white blood cells in peripheral blood were counted and classified, and the number of white blood cells in bronchus alveolar lavage fluid were counted. The pathological changes of lung tissue were observed by HE staining and the number of dust cells was counted. The expression of leukocyte differentiation antigen 163 (CD163) in lung tissue were determined by immunohistochemical method. RESULTS: The white blood cells in peripheral blood mainly included lymphocyte and neutrophil, of which lymphocyte is the main one. Compared with blank control group, there was no statistical significance in the number of white blood cells, lymphocyte or neutrophil in peripheral blood, the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in normal saline group (P>0.05); the structures of bronchus and lung tissue were intact, and the expression of CD163 was negative. Compared with normal saline group, there was no statistical significance in the above indexed of rats in budesonide group(P>0.05), the structures of bronchus and lung tissue were intact, and the expression of CD163 was negative, while the number of white blood cells, lymphocyte or neutrophil in peripheral blood, the number of white blood cells in alveolar lavage fluid or the number of dust cells in lung tissue of rats in other 5 groups were all increased significantly (P<0.05); alveolar wall thickening and alveolar interstitial edema occurred in different degrees in lung tissue. The expression of CD163 was positive or strongly positive. CONCLUSIONS: The long-term aerosol inhalation of 4 kinds of non-aerosol drugs can induce pathological changes of lung tissue and increase the number of inflammatory cell and dust cell in alveolin in healthy SD rats.
		                        		
		                        		
		                        		
		                        	
2.Effect of Yanghe decoction serum on the proliferation of breast cancer stem cells
Kai YE ; Fenli HE ; Xiaojuan YANG ; Rongguo SHANG ; Kangle LI ; Jiansheng QIAN ; Jianwei DOU
International Journal of Traditional Chinese Medicine 2019;41(1):49-52
		                        		
		                        			
		                        			Objective To investigate the effect of Yanghe decoction serum on the proliferation of breast cancer stem cells HMLER90hi and its mechanism. Methods Twenty female Sprague-Dawley rats were randomly divided into low,medium and high dose groups containing drug serum and control group, in order to prepare the Yanghe decoction serum and blank serum. After 24 hours of drug intervention,the effects of each group on the proliferation of HMLER90hi cells at 24 h,48 h,and 72 h were detected by MTT assay. The expression of EphA4 and p50 mRNA in each group were detected by real-time fluorescence quantitative PCR. Results Compared with the blank control group,the cell proliferation activity of each dose group of Yanghe decoction significantly decreased at 24 h (0.818 ± 0.061, 0.706 ± 0.073, 0.587 ± 0.052 vs. 0.928 ± 0.075), 48h (0.760 ± 0.047, 0.638 ± 0.056, 0.510 ± 0.059 vs. 0.973 ± 0.095), and 72 h (0.672 ± 0.102, 0.508 ± 0.092, 0.448 ± 0.048vs.1.023 ± 0.099) (P<0.05 orP<0.01), respectively. After 24 h of drug intervention, compared with the control group, the expression of EphA4 mRNA (0.54 ± 0.07, 0.54 ± 0.07, 0.33 ± 0.04 vs.0.68 ± 0.09) significantly decreased, and p50 mRNA (0.69 ± 0.10, 0.54 ± 0.08, 0.41 ± 0.06vs. 0.85 ± 0.13) significantly decreased in each dose group of Yanghe decoction (P<0.05 orP<0.01).ConclusionsTheYanghe decoction can inhibit the proliferation of breast cancer stem cell HMLER90hi,and its mechanism may be related to its inhibition of the conduction of the juxtacrine pathway of monocyte macrophage.
		                        		
		                        		
		                        		
		                        	
3.Effect of different drugs inhalation on SD rats lung tissue
Qian HE ; Rongguo TANG ; Fancai LI ; Xiujuan WANG ; Bin LI ; Xiaodan SONG ; Weilin OU
Chinese Journal of Applied Clinical Pediatrics 2019;34(4):295-299
		                        		
		                        			
		                        			Objective To have SD rats inhaled with different drugs,and observe their lung pathological change of lungs through light microscopy,in order to evaluate the safety of different drugs inhaled by natural rats. Methods A total of 40 rats were randomly divided into 8 groups,and every group had 5 rats,including blank control groups,9 g/L saline group,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Centamicin group,Danshen group,Silicon dioxide group,twice a day,last 56 days totally. Then,blood and bronchoalveolar lavage fluid were collected and analyzed for cell count,percent of each type of cell,to measure the severity of the inflammation. Additionally,histopathology re-vealed the lungˊs pathological change and the number of dust cell;while immunohistochemistry revealed CD163 respon-ding. Results (1)White blood cell count:blank control group(3. 96 ± 0. 36)×109/L,9 g/L saline group(4. 66 ± 0. 58)×109/L,Salbutamol group(4. 06 ± 0. 86)×109/L,Dingchuantang group(8. 98 ± 1. 08)×109/L,Shuanghuang-lian group(7. 10 ± 0. 88)×109/L,Centamicin group(6. 14 ± 0. 89)×109/L,Danshen group(9. 84 ± 2. 33)×109/L, Silicon dioxide group(8. 99 ± 2. 48)×109/L,and comparative analysis of the 8 groups had significant difference(F=14. 530,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not sig- nificant(all P>0. 05). White cell count in BALF:blank control group(2. 16 ± 1. 04)×109/L,9 g/L saline group (3. 94 ± 0. 67)×109/L,Salbutamol group(4. 36 ± 1. 15)×109/L,Dingchuantang group(14. 58 ± 2. 93)×109/L, Shuanghuanglian group(19. 68 ± 6. 29)×109/L,Gentamicin group(11. 74 ± 1. 03)×109/L,Danshen group(44. 75 ± 10. 8)×109/L,Silicon dioxide group(53. 54 ± 14. 25)×109/L,and comparative analysis of the 8 groups had signifi-cant difference(F=40. 616,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05). Lymphocyte count in BALF:blank control group(18. 70 ± 9. 00)×108/L, 9 g/L saline group( 36. 01 ± 5. 99 )×108/L,Salbutamol group( 38. 95 ± 11. 69 )×108/L,Dingchuantang group (132. 70 ± 26. 94)×108/L,Shuanghuanglian group(173. 56 ± 57. 6)×108/L,Gentamicin group(106. 60 ± 16. 76)× 108/L,Danshen group(340. 63 ± 70. 97)×108/L,Silicon dioxide group(495. 63 ± 131. 95)×108/L,and comparative analysis of the 8 groups had significant difference(F=41. 980,P<0. 05);the differences among blank control group, 9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(2)Number of lung dust cell count in 10 sight of high light microscopy:blank control group 12/10 HP,9 g/L saline group 26/10 HP,Salbutamol group 17/10 HP,Dingchuantang group 262/10 HP,Shuanghuanglian group 133/10 HP,Gentamicin group 109/10 HP,Danshen group 96/10 HP,Silicon dioxide group 315/10 HP,and comparative analysis of the 8 groups had significant difference (F=69. 915,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(3)Hematoxylin-eosin staining of lung:blank control group,9 g/L saline group and Sal-butamol group had no pathological change in the lung,but Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Silicon dioxide group had pathological changes in different degrees.(4) Immunohistochemistry of CD163 responding:blank control group,9 g/L saline group and Salbutamol group had negative expression,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Sili-con dioxide group had positive expression in different degrees. Conclusions 9 g/L saline,salbutamol for atomized inhalation does not cause lung tissue damage;Long-term use of non-atomized drugs in atomization can cause lung tissue injury in SD rats,and the severity varies with specific drugs.
		                        		
		                        		
		                        		
		                        	
4.Influence of pulmonary hypertension on patients with advanced chronic obstrnctive pulmonary disease prior to lung transplantation
Wenjun MAO ; Jingyu CHEN ; Mingfeng ZHENG ; Ruo CHEN ; Yijun HE ; Feng LIU ; Shugao YE ; Rongguo LU
Chinese Journal of Organ Transplantation 2018;39(9):553-558
		                        		
		                        			
		                        			Objective To study the influence of pulmonary artery hypertension (PAH) on survival of patients with advanced chronic obstructive pulmonary disease (COPD) on the waiting list of lung transplantation.Methods The characteristics of 143 patients with COPD receiving lung transplantation evaluation from January 2014 to August 2016 were queried.Mild PAH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg and severe ≥35 mrnHg by right heart catheterization measurements.The incidence of PAH was studied,and the patients were divided to different groups to determine the effect of PAH on survival prior to transplantation on the basis of different definitions of PAH.Kaplan Meier method was used to draw survival curves,and a log-rank test was used to analyze the effect of PAH on survival of COPD patients on the waiting list of pulmonary transplantation.Univariate and multivariate Cox proportional hazard models were performed to test the relationship between each main covariate and the hazard of mortality.The waiting time was tracked from wait list entry date until death or censoring,and the censoring issues were as follows:receiving lung transplantation,removing from the waiting list without transplant,and still wating for donor until the last follow-up day (2016-08-30).Results Of 143 COPD patients,there were 119 males and 24 males,with mean age of 61.73 years old;46 patients received lung transplantation,and the remaining 97 not;50 had mPAP ≥25 mmHg and 21 had mPAP ≥35 mmHg.A total of 23 cases (22.88%) died on the waiting list.Thirty-eight patients were removed from the list prior to transplantation,and 36 were still on the waiting list.Kaplan-Meier survival function showed suvival of patients with mild PAH or severe PAH was significantly shorter than that of patients without PAH (P<0.001).Using Cox proportional hazards models,univariate analysis revealed significant differences in survival for mild PAH (HR =2.147,95%CI 1.429-3.157,P< 0.001) and severe PAH (HR =3.458,95 % CI 2.518-4.859,P<0.001).Multivariate Cox models identified significant risk for death for mild PAH (HR=2.518,95%CI 1.728-3.364,P<0.001) and severePAH HR=4.027,95% CI 3.257-4.703,P<0.001).Conclusion The incidence of PAH among COPD patients waiting for lung transplantation was high.PAH is associated with significantly increased risk of death among COPD patients waiting for lung transplantation.
		                        		
		                        		
		                        		
		                        	
5.Lung transplantation for end-stage pulmonary diseases using donation after death of citizens: report of 242 cases
Wenjun MAO ; Jingyu CHEN ; Mingfeng ZHENG ; Feng LIU ; Shugao YE ; Ruo CHEN ; Yijun HE ; Rongguo LU
Chinese Journal of Organ Transplantation 2017;38(11):676-681
		                        		
		                        			
		                        			Objective To summarize the lung transplant program using donation after death of citizens (DCD).Methods Retrospective characteristics of 242 patients with end-stage lung diseases receiving lung transplantation in our hospital were reviewed between January 2015 and December 2016.The data about evaluation and collection of all donors were analyzed.The survival rate,causes of deaths,and postoperative complications were reviewed.Kaplan Meier survival curves and a logrank test of differences in survival functions were used to assess the effect of lung transplant type and extracorporeal membrane oxygenation (ECMO) on survival post transplant.Results A total of 231 patients donated their lungs,including China type three (135 cases),China type two (19 cases),and China type one (77 cases).242 lung transplantations were successfully performed.The 3-month,6-month and 1-year survival rate after lung transplantation was 80.6%,80.6%,and 77.8%,respectively.There were 47 deaths during perioperative period,including 22 cases of primary graft dysfunction,14 cases of sepsis,6 cases of multiple organ failure,3 cases of heart failure,and 2 cases of stomal leak.One hundred and thirty-two patients received bilateral lung transplantation,with 3-month,6-month,and 1-year survival rate being 78.6%,78.6%,and 75.6% respectively.110 underwent single lung transplantation with 3-month,6-month,and 1-year survival rate being 82.7 %,82.7 %,and 80.1%,respectively.No significant difference in survival rate was observed between single and bilateral lung transplantation (P>0.05).One hundred and twenty-nine cases of lung transplants were conducted under ECMO support,with the 3-month,6-month and 1-year survival rate being 72.5%,72.5%,and 70.5% respectively,which was significantly higher in those without ECMO with the 3-month,6-month and 1-year survival rate being 90.2%,90.2% and 86.6% respectively (n =113) (P < 0.05).Conclusion DCD may facilitate the development of lung transplantation in China with long-term survival.
		                        		
		                        		
		                        		
		                        	
6.Lung transplantation for phase Ⅲ silicosis:a series of 32 cases
Wenjun MAO ; Jingyu CHEN ; Mingfeng ZHENG ; Ruo CHEN ; Yijun HE ; Feng LIU ; Shugao YE ; Rongguo LU
Chinese Journal of Surgery 2016;54(12):902-907
		                        		
		                        			
		                        			Objective To evaluate the effect of lung transplantation for phase Ⅲ silicosis?Methods From September 2002 to September 2015, 32 patients with end?stage silicosis underwent lung transplantation at Department of Thoracic Surgery, Affiliated Wuxi People′s Hospital, Nanjing Medical University? There were 29 male and 3 female patients aged from 24 to 63 years? Thirty?two patients were diagnosed as phase Ⅲ silicosis by the local occupational disease prevention and control center? Fifteen patients were type Ⅰrespiratory failure and 17 patients were typeⅡ? There were 14 cases accepted bilateral sequential lung transplantation and 18 cases accepted single lung transplantation, including 13 cases with right single lung transplantation and 5 cases with left single lung transplantation? Extracorporeal membrane oxygenation was used in 13 patients? Pulmonary function monitoring was performed at 3 months,6 months, 1 year,and 2 years after lung transplantation? Clinical characteristics were compared using t?test,χ2 test and Fisher exact test between groups, Kaplan?Meier survival curve and Log?rank test were used to find out the factors affecting survival? Results All the patients received lung transplantation successfully? One patient died of multiple organ failure, 1 died of sepsis, and 1 succumbed to sudden cardiac death? Twenty?nine patients were discharged from hospital? During follow?up, there were 5 deaths, two patients died of sepsis 7 months postoperatively, 1 died of renal failure 5 months post?transplant, 1 died of sudden cardiac death, and the remaining 1 patient died of bronchiolitis obliterans? Twenty?four patients lived a good quality of life, with survival rates of 90?6% at 3 months, 80?8% at 1 year, 76?7% at 3 years, and 76?7% at 5 years?Significant difference was not observed between single and bilateral lung transplantation about long?term survival rate? During follow?up pulmonary function post?transplant ( 3 months, 6 months, 1 year, and 2 years) were improved dramatically compared with preoperative level, and patients lived a good quality of life? Conclusion Lung transplantation is beneficial for patients with phase Ⅲ silicosis, long?term survival is probable.
		                        		
		                        		
		                        		
		                        	
7.Lung transplantation for phase Ⅲ silicosis:a series of 32 cases
Wenjun MAO ; Jingyu CHEN ; Mingfeng ZHENG ; Ruo CHEN ; Yijun HE ; Feng LIU ; Shugao YE ; Rongguo LU
Chinese Journal of Surgery 2016;54(12):902-907
		                        		
		                        			
		                        			Objective To evaluate the effect of lung transplantation for phase Ⅲ silicosis?Methods From September 2002 to September 2015, 32 patients with end?stage silicosis underwent lung transplantation at Department of Thoracic Surgery, Affiliated Wuxi People′s Hospital, Nanjing Medical University? There were 29 male and 3 female patients aged from 24 to 63 years? Thirty?two patients were diagnosed as phase Ⅲ silicosis by the local occupational disease prevention and control center? Fifteen patients were type Ⅰrespiratory failure and 17 patients were typeⅡ? There were 14 cases accepted bilateral sequential lung transplantation and 18 cases accepted single lung transplantation, including 13 cases with right single lung transplantation and 5 cases with left single lung transplantation? Extracorporeal membrane oxygenation was used in 13 patients? Pulmonary function monitoring was performed at 3 months,6 months, 1 year,and 2 years after lung transplantation? Clinical characteristics were compared using t?test,χ2 test and Fisher exact test between groups, Kaplan?Meier survival curve and Log?rank test were used to find out the factors affecting survival? Results All the patients received lung transplantation successfully? One patient died of multiple organ failure, 1 died of sepsis, and 1 succumbed to sudden cardiac death? Twenty?nine patients were discharged from hospital? During follow?up, there were 5 deaths, two patients died of sepsis 7 months postoperatively, 1 died of renal failure 5 months post?transplant, 1 died of sudden cardiac death, and the remaining 1 patient died of bronchiolitis obliterans? Twenty?four patients lived a good quality of life, with survival rates of 90?6% at 3 months, 80?8% at 1 year, 76?7% at 3 years, and 76?7% at 5 years?Significant difference was not observed between single and bilateral lung transplantation about long?term survival rate? During follow?up pulmonary function post?transplant ( 3 months, 6 months, 1 year, and 2 years) were improved dramatically compared with preoperative level, and patients lived a good quality of life? Conclusion Lung transplantation is beneficial for patients with phase Ⅲ silicosis, long?term survival is probable.
		                        		
		                        		
		                        		
		                        	
8.Th17/Treg imbalance in the peripheral blood of patients with psoriasis vulgaris
Rongguo HE ; Shaoguo WU ; Hua TIAN ; Qinxue WU ; Yunxue WU
Chinese Journal of Dermatology 2011;44(6):411-414
		                        		
		                        			
		                        			Objective To investigate the imbalance between T helper 17 (Th17) cells and CD4+CD25+ regulatory T (Treg) cells in the peripheral blood of patients with psoriasis vulgaris and its significance. Methods Peripheral blood were collected from 48 patients with psoriasis vulgaris and 32 normal human controls. Pasoriasis area and severity index (PASI) was used to assess the disease severity in these patients. Flow cytometry was performed to determine the percentage of Th17 and Treg cells in peripheral blood, enzyme linked immunosorbent assay (ELISA) to measure the levels of serum interleukin (IL) -17 and IL-10. Results There was a significant increase in the percentage of Th17 cells [(2.70 ± 1.43)% vs. (0.86 ± 0.25)%, P< 0.01] and serum IL-17 level (90.65 ± 29.61 ng/L vs. 48.82 ± 5.49 ng/L, P < 0.01), but a decrease in the percentage of Treg cells [(3.63 ± 1.14)% vs. (7.87 ± 1.26)%, P< 0.01] and serum IL-10 level (17.78 ± 4.09 ng/L vs. 23.76 ± 3.82 ng/L, P <0.01) in patients with psoriasis vulgaris compared with the normal controls. The ratios of Thl7 to Treg cells and serum IL-17 to IL-10 level were significantly higher (0.95 ± 0.76 vs. 0.12 ± 0.06, 5.78 ± 3.19 vs. 2.16 ±0.68, both P < 0.01) in the patients than in the normal controls. The PASI score in patients was positively correlated with the percentage of Th17, serum level of IL-17, Th17/Treg ratio and IL-17/IL-10 ratio (r = 0.97,0.93, 0.99 and 0.97, all P < 0.01), but negatively correlated with the percentage of Treg cells and serum IL-10 level (r = -0.87, -0.90, both P < 0.01). Conclusion The imbalance between Th17 and Treg cells may play an important role in the pathogenesis of psoriasis vulgaris.
		                        		
		                        		
		                        		
		                        	
9.Prevention of bronchopulmonary complications by ambroxol after thoracotomy in patients with chronic obstructive pulmonary disease
Xingfeng ZHU ; Mingfeng ZHENG ; Jingyu CHEN ; Yijun HE ; Ruo CHEN ; Qiankun ZHU ; Shugao YE ; Feng LIU ; Rongguo LU
Chinese Journal of Geriatrics 2011;30(12):1000-1002
		                        		
		                        			
		                        			Objective To evaluate the effects of ambroxol on prevention of bronchopulmonary complications after thoracotomy in patients with chronic obstructive pulmonary disease(COPD).MethodsTotal 161 elderly patients aged ≥70 years with COPD undergoing thoracotomy were randomly allocated to two groups:ambroxol group (300 mg/d,6 d) and placebo group as control.Pulmonary complications were evaluated by clinical symptoms,radiographic changes,and blood gas analysis. Results The incidence rates of atelectasis were 8.6% in ambroxol group and 28.8% in placebo group,respectively.The PaO2 values after surgery in ambroxol group decreased more than in placebo group (P<0.05) compared with the preoperative values.Side effects were not found in all patients.Conclusions Ambroxol should be considered as an alternative pharmacologic approach for the prevention of post-thoracotomy pulmonary complications in the elderly patients with COPD.
		                        		
		                        		
		                        		
		                        	
10.The expression of heparanase in non-melanoma skin cancer and its clinical significance
Rongguo HE ; Dongqi ZOU ; Hua TIAN ; Qingxue WU ; Yunxue WU
Journal of Chinese Physician 2010;12(8):1041-1044
		                        		
		                        			
		                        			Objective To investigate the expression of heparanase in non-melanoma skin cancer including cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC) and the relationship among heparanase expression and pathologic grading and lymph nodes metastasis of CSCC. Methods The expressions of heparanase were detected by RT-PCR assay and immunohistochemical staining in 38 cases of CSCC, 33 BCC and 19 normal human skin tissues. Then the relationship between heparanase expression and CSCC clinical pathological features was explored. Results The positive rate ( 68.4%, 60. 5% ) of heparanase mRNA and heparanase in CSCC (24. 2%, 18. 2% ) was significantly higher than those of BCC and normal skin tissue ( 10. 5% ,5.3% ) ( P <0. 01 ) . Heparanase expression rate in CSCC with lymph nodes metastasis (92. 3% ,84.6% ) and Ⅲ~Ⅳ(Broders) (92. 3% ,84. 6% ) was higher than those in tumor without lymph nodes metastasis (56. 0% ,48.0% ) and Ⅰ~Ⅱ (Broders) (56. 0% ,48. 0% ) ( P <0. 05). Conclusions Heparanase was over-expressed in CSCC compared with BCC and normal skin tissues. Expression of heparanase was correlated to pathologic grade and lymph nodes metastasis of CSCC.
		                        		
		                        		
		                        		
		                        	
            
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