1.Emodin attenuates severe acute pancreatitis-associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation.
Qian HU ; Jiaqi YAO ; Xiajia WU ; Juan LI ; Guixiang LI ; Wenfu TANG ; Jingping LIU ; Meihua WAN
Acta Pharmaceutica Sinica B 2022;12(10):3986-4003
		                        		
		                        			
		                        			Severe acute pancreatitis-associated acute lung injury (SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI; however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely, emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury, and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.
		                        		
		                        		
		                        		
		                        	
2.Role of neutrophil extracellular traps in inflammatory evolution in severe acute pancreatitis
Hongxin KANG ; Yue YANG ; Lv ZHU ; Xianlin ZHAO ; Juan LI ; Wenfu TANG ; Meihua WAN
Chinese Medical Journal 2022;135(23):2773-2784
		                        		
		                        			
		                        			Severe acute pancreatitis (SAP) is a life-threatening acute abdominal disease with two peaks of death: the first in the early stage, characterized by systemic inflammatory response-associated organ failure; and the second in the late stage, characterized by infectious complications. Neutrophils are the main immune cells participating in the whole process of SAP. In addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens, neutrophil extracellular traps (NETs) also play an important roles in inflammatory reactions. We reviewed the role of NETs in the occurrence and development of SAP and its fatal complications, including multiple organs injury, infected pancreatic necrosis, and thrombosis. This review provides novel insights into the involvement of NETs throughout the entire process of SAP, showing that targeting NETs might be a promising strategy in SAP treatment. However, precision therapeutic options targeting NETs in different situations require further investigation.
		                        		
		                        		
		                        		
		                        	
3.Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses.
Qian HU ; Christopher J LYON ; Jesse K FLETCHER ; Wenfu TANG ; Meihua WAN ; Tony Y HU
Acta Pharmaceutica Sinica B 2021;11(6):1493-1512
		                        		
		                        			
		                        			Macrophages are typically identified as classically activated (M1) macrophages and alternatively activated (M2) macrophages, which respectively exhibit pro- and anti-inflammatory phenotypes, and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation, injury, and repair processes. Recent studies indicate that tissue cells and macrophages interact
		                        		
		                        		
		                        		
		                        	
4. Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study
Yike WAN ; Wei SANG ; Bing CHEN ; Yonggong YANG ; Luqin ZHANG ; Aining SUN ; Yuejun LIU ; Yang XU ; Yipeng CAI ; Chunbin WANG ; Yunfeng SHEN ; Yangwen JIANG ; Xiaoyan ZHANG ; Wei XU ; Ming HONG ; Tao CHEN ; Ruirong XU ; Feng LI ; Yanli XU ; Yan XUE ; Yilong LU ; Zhengmei HE ; Weimin DONG ; Ze CHEN ; Meihua JI ; Yueyan YANG ; Lijia ZHAI ; Yu ZHAO ; Guangqi WU ; Jiahua DING ; Jian CHENG ; Weibo CAI ; Yumei SUN ; Jian OUYANG
Chinese Journal of Hematology 2017;38(7):602-606
		                        		
		                        			 Objective:
		                        			To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment.
		                        		
		                        			Methods:
		                        			Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed.
		                        		
		                        			Results:
		                        			The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) .
		                        		
		                        			Conclusions
		                        			Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%. 
		                        		
		                        		
		                        		
		                        	
5.Dachengqi Decoction induces pancreatic acinar cell apoptosis in experimental acute pancreatitis in rats.
Yanyi REN ; Hanlin GONG ; Wenfu TANG ; Meihua WAN ; Jianlei ZHAO ; Xi HUANG
Journal of Integrative Medicine 2009;7(7):651-6
		                        		
		                        			
		                        			To explore the effects of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine, on pancreatic acinar cell apoptosis in a rat model of experimental acute pancreatitis.
		                        		
		                        		
		                        		
		                        	
6.Effects of ranitidine on pharmacokinetics of rhein from Dachengqi Decoction in rats after oral administration.
Yanyi REN ; Hanlin GONG ; Wenfu TANG ; Meihua WAN ; Xi HUANG
Journal of Integrative Medicine 2009;7(9):868-72
		                        		
		                        			
		                        			Objective: To explore the effects of ranitidine on pharmacokinetics of rhein in rats after oral administration of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine. Methods: Twelve male Sprague-Dawley rats were divided into DCQD group and DCQD plus ranitidine group, and were orally administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series of time intervals. Metabolism of rhein was determined with a reversed-phase high-performance liquid chromatography with internal standard of 1, 8-dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The pharmacokinetic parameters were compared between the two groups. Results: The pharmacokinetic parameters of rhein in the DCQD group, including peak concentration (C(max)), area under the plasma concentration-time curve (AUC), distribution phase half-life (t(1/2alpha)), elimination rate constant (K(10)) and central to peripheral transfer rate constant (K(12)), were significantly different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were no significant differences in the other parameters between the two groups. Conclusion: Ranitidine can influence the pharmacokinetics of rhein in rats after oral administration of DCQD.
		                        		
		                        		
		                        		
		                        	
7.Non-preventive use of antibiotics in patients with severe acute pancreatitis treated with integrated traditional Chinese and Western medicine therapy: a randomized controlled trial.
Xiaonan YANG ; Lihui DENG ; Ping XUE ; Long ZHAO ; Tao JIN ; Meihua WAN ; Qing XIA
Journal of Integrative Medicine 2009;7(4):330-3
		                        		
		                        			
		                        			To investigate the prognostic effects of integrated traditional Chinese and Western medicine therapy without antibiotics in treatment of patients with severe acute pancreatitis (SAP).
		                        		
		                        		
		                        		
		                        	
8.Chaiqin Chengqi Decoction decreases pancreatic acinar cell calcium overload in rats with acute pancreatitis
Ping XUE ; Lihui DENG ; Zhaoda ZHANG ; Xiaonan YANG ; Qing XIA ; Dakai XIANG ; Lei HUANG ; Meihua WAN ; Haiyan ZHANG
Journal of Integrative Medicine 2008;6(10):1054-8
		                        		
		                        			
		                        			OBJECTIVE: To investigate the mechanism of Chaiqin Chengqi Decoction (CQCQD), a compound of traditional Chinese herbal medicine, acting on the pancreatic acinar cell calcium overload in rats with acute pancreatitis (AP). METHODS: A total of 30 SD rats were randomly divided into normal control group, untreated group and CQCQD group (n=10, respectively). AP was induced in rats by caerulein (5x50 mug/kg) intraperitoneal injection within 4 h. The pancreatic tissue SERCA1 and SERCA2 mRNA expressions were detected by fluorescent quantization polymerase chain reaction method; intracellular calcium fluorescence intensity (FI) of pancreatic acinar cells and the pancreatic pathological score were measured by laser scanning confocal microscopy and light microscopy respectively. RESULTS: There were no SERCA1 mRNA expressions in pancreatic acinar cells of rats in the normal control group and the untreated group. The expression of pancreatic SERCA2 mRNA in the untreated group was down-regulated compared with that in the normal control group (expression ratio=0.536; P=0.001); the expression of pancreatic SERCA2 mRNA in the CQCQD group was up-regulated compared with that in the untreated group (expression ratio=2.00; P=0.012). The pancreatic pathological score in the CQCQD group was lower than that in the untreated group and the FI of Ca(2+) was also lower. CONCLUSION: CQCQD can up-regulate the expression of pancreatic SERCA2 mRNA, release the calcium overload, and hence reduce the pathological changes in pancreatic tissue.
		                        		
		                        		
		                        		
		                        	
9.A study of the mechanism of Qingre Huatan therapy in treatment of acute exacerbation of chronic obstructive pulmonary disease by improving airway inflammation and mucus hypersecretion
Weng LI ; Bing MAO ; Gang WANG ; Lei WANG ; Jing CHANG ; Ying ZHANG ; Meihua WAN ; Jia GUO
Journal of Integrative Medicine 2008;6(8):799-805
		                        		
		                        			
		                        			OBJECTIVE: To explore the effects of Tanreqing injection, a traditional Chinese herbal preparation for clearing heat and resolving phlegm, in treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by improving airway inflammation and airway mucus hypersecretion. METHODS: A randomized controlled trial (RCT) was designed. Ninety AECOPD patients were randomly divided into Tanreqing group, ambroxol hydrochloride group and control group. The patients in the three groups were all treated with conventional therapy. Furthermore, intravenous drip infusion of 20 ml Tanreqing injection (once daily) and 15 mg ambroxol hydrochloride injection (twice daily) were administered respectively to the patients in the Tanreqing group and ambroxol hydrochloride group. They were all treated for 10 days. Symptom score of traditional Chinese medicine (TCM), plasma concentrations of interleukin-8 (IL-8), IL-10 and neutrophil elastase (NE) were detected before and after treatment. RESULTS: Cough, sputum amount, expectoration, dyspnea, fever, coated tongue and pulse tracings were improved obviously in Tanreqing group (P<0.05), and the effects of Tanreqing on improving cough, sputum amount and expectoration were better than the conventional therapy (P<0.05), while there was no significant difference between Tanreqing group and ambroxol hydrochloride group (P>0.05). Compared with ambroxol hydrochloride group and the control group, the coated tongue was improved obviously in Tanreqing group (P>0.05). After treatment, plasma concentrations of IL-8, IL-10 and NE were decreased in Tanreqing group and ambroxol hydrochloride group (P<0.05), and the levels of IL-8 and IL-10 in the control group were decreased (P<0.05). The change of IL-8 level before and after treatment in Tanreqing group was greater than that in ambroxol hydrochloride group and the control group. The changes of IL-10 and NE levels in ambroxol hydrochloride group were greater than those in Tanreqing group and the control group, while there was no significant difference in the changes of serum levels of IL-8, IL-10 and NE among the three groups (P>0.05). Total response rates in Tanreqing group and ambroxol hydrochloride group were higher than that in the control group (P<0.05), while there was no significant difference in total response rate between Tanreqing group and ambroxol hydrochloride group (P>0.05). There was no significant difference in total response rate among the three groups (P>0.05). CONCLUSION: Tanreqing injection can improve TCM signs and symptoms in AECOPD patients, and the mechanism maybe due to the decrease of serum levels of IL-8 and NE and improvement of IL-10 level.
		                        		
		                        		
		                        		
		                        	
10.SNP767A/T of FUS2 gene and lung cancer risk in Chinese population.
Xinhua MU ; Kang SHAO ; Cuiyan ZHANG ; Zhaoli CHEN ; Junting WAN ; Kezhi ZHANG ; Ning LI ; Fang ZHOU ; Meihua XIONG ; Jie HE
Chinese Journal of Lung Cancer 2006;9(5):409-412
BACKGROUNDFUS2 gene locating at 3p21.3 is considered a promising candidate tumor suppressor gene. The aim of this study is to examine the difference in FUS2-767A/T polymorphism site between lung cancer patients and normal controls in Chinese population.
METHODSThe genotype FUS2-767A/T was detected in 146 lung cancer patients and 113 normal controls by PCR-SSCP method. The relationship between lung cancer risk and difference in genotypes of FUS2 gene was analysed.
RESULTSFUS2-767A/T was significantly related to histological type (P=0.044), age of the patients with lung cancer (P=0.011) and vessel cancer embolus (P=0.031) in lung cancer group. There was no significant difference in distribution of FUS2 genotypes between lung cancer patients and normal controls (P=0.945).
CONCLUSIONSThe results suggest that the FUS2-767A/T polymorphism may be a susceptibility factor for lung cancer among Chinese population.
            
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