1.Clinical Study on Yiqi Huatan Tongluo Prescription Combined with Drug-Coated Balloon in the Treatment of Coronary Heart Disease of Qi Deficiency and Phlegm Stasis Obstructing Collateral Type
Mei-Chun HUANG ; Yu-Peng LIANG ; Pei-Zhong LIU ; Sheng-Yun ZHANG ; Se PENG ; Chuang-Peng LI ; He-Zhen ZHANG ; Tian-Wei LAI ; Chang-Jiang AI ; Qing LIU ; Ai-Meng ZHANG ; Shao-Hui LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(10):2656-2662
		                        		
		                        			
		                        			Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68%(47/53),and that of the control group was 75.47%(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P<0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P>0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P<0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P<0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87%(10/53),and that in the control group was 20.75%(11/53).There was no significant difference between the two groups(P>0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.
		                        		
		                        		
		                        		
		                        	
2.Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice.
Xiaoqing FAN ; Chutian MAI ; Ling ZUO ; Jumin HUANG ; Chun XIE ; Zebo JIANG ; Runze LI ; Xiaojun YAO ; Xingxing FAN ; Qibiao WU ; Peiyu YAN ; Liang LIU ; Jianxin CHEN ; Ying XIE ; Elaine Lai-Han LEUNG
Acta Pharmaceutica Sinica B 2023;13(3):1164-1179
		                        		
		                        			
		                        			Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.
		                        		
		                        		
		                        		
		                        	
3.Erratum: Author correction to 'Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice' Acta Pharmaceutica Sinica B 13 (2023) 1164-1179.
Xiaoqing FAN ; Chutian MAI ; Ling ZUO ; Jumin HUANG ; Chun XIE ; Zebo JIANG ; Runze LI ; Xiaojun YAO ; Xingxing FAN ; Qibiao WU ; Peiyu YAN ; Liang LIU ; Jianxin CHEN ; Ying XIE ; Elaine LAI-HAN LEUNG
Acta Pharmaceutica Sinica B 2023;13(8):3575-3576
		                        		
		                        			
		                        			[This corrects the article DOI: 10.1016/j.apsb.2022.10.016.].
		                        		
		                        		
		                        		
		                        	
4.Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.
Li Rong HONG ; Yu Jia CHEN ; Qing Lai JIANG ; Ru Lin JIA ; Chun LI ; Liang Hua FENG
Journal of Peking University(Health Sciences) 2023;55(6):1033-1038
		                        		
		                        			OBJECTIVE:
		                        			To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.
		                        		
		                        			METHODS:
		                        			A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.
		                        		
		                        			RESULTS:
		                        			Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.
		                        		
		                        			CONCLUSION
		                        			TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Antiphospholipid Syndrome/diagnosis*
		                        			;
		                        		
		                        			Tissue Plasminogen Activator
		                        			;
		                        		
		                        			Thrombosis/etiology*
		                        			;
		                        		
		                        			Antibodies, Antiphospholipid/analysis*
		                        			;
		                        		
		                        			Blood Coagulation Tests/adverse effects*
		                        			
		                        		
		                        	
5.Prevention from PICC-related venous thrombosis in the upper limbs of malignant tumor patients with moxibustion combined with plucking at Jiquan (HT 1): a randomized controlled trial.
Ling QIU ; Xiao-Yi LIANG ; Yu-Ling ZHENG ; Chun-Xiang LIU ; Xiao-Qing LAI ; Li-Ying ZHU
Chinese Acupuncture & Moxibustion 2022;42(7):741-746
		                        		
		                        			OBJECTIVE:
		                        			To observe the clinical effect of moxibustion combined with plucking technique at Jiquan (HT 1) for preventing peripherally inserted central catheter (PICC)-related venous thrombosis in the upper limbs of malignant tumor patients.
		                        		
		                        			METHODS:
		                        			A total of 80 malignant tumor patients undergoing PICC were randomized into an observation group and a control group, 40 cases in each one. In the control group, the routine care for PICC was exerted. In the observation group, besides the routine care, moxibustion combined with plucking technique at Jiquan (HT 1) was added. Mild moxibustion was exerted along the venous distribution of PICC (avoiding the entry site) for 10 to 15 min, and then, the circling moxibustion was applied to Quchi (LI 11), Xuehai (SP 10) and Tianfu (LU 3), 3 to 5 min at each acupoint. Finally, plucking technique was given at Jiquan (HT 1) for 5 to 10 min. This combined therapy was intervened since the 2nd day of PICC placement, once daily, 5 times a week, for 3 weeks totally. The incidence of the PICC-related venous thrombosis in the upper limbs was compared between the two groups on day 42 of placement. On day 2, 7, 14, 21, 28, 35 and 42 of PICC placement, the peak systolic velocity (PSV) and the end-diastolic velocity (EDV) of the subclavicular vein on the placement side were observed separately in the two groups.
		                        		
		                        			RESULTS:
		                        			The incidence of the PICC-related venous thrombosis in the upper limbs in the observation group was lower than that in the control group (2.5% [1/40] vs 17.5% [7/40], P<0.05). From day 7 to 35 of PICC placement, PSV of the subclavicular vein on the placement side was higher than that on the day 2 of PICC placement in the observation group (P<0.05). On day 28 and 42 of PICC placement, PSV of the subclavicular vein on the placement side was lower than that on the day 2 of PICC placement in the control group (P<0.05). In the observation group, EDV of the subclavicular vein on the placement side was higher than that on the day 2 of PICC placement from day 7 to 28 of PICC placement (P<0.05). In the control group, EDV of the subclavicular vein on the placement side from day 28 to 42 of PICC placement was lower than that on the day 2 of PICC placement (P<0.05). From day 7 to 42 of PICC placement, PSV and EDV of the subclavicular vein on the placement side in the observation group were all higher than those in the control group (P<0.01, P<0.05).
		                        		
		                        			CONCLUSION
		                        			The combined treatment of moxibustion with plucking technique at Jiquan (HT 1) can effectively prevent PICC-related venous thrombosis in the upper limbs and improve venous blood flow velocity in malignant tumor patients.
		                        		
		                        		
		                        		
		                        			Catheterization, Central Venous/methods*
		                        			;
		                        		
		                        			Catheterization, Peripheral/adverse effects*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Moxibustion/adverse effects*
		                        			;
		                        		
		                        			Neoplasms/complications*
		                        			;
		                        		
		                        			Upper Extremity
		                        			;
		                        		
		                        			Venous Thrombosis/etiology*
		                        			
		                        		
		                        	
6. Comparative study on ultrasonic diagnosis and pathological anatomy of congenital absent semilunar valve in first trimester
Shuihua YANG ; Mengfeng LIANG ; Guican QIN ; Zuojian YANG ; Xinyan LI ; Xueqin LI ; Xiaoxian TIAN ; Chun HE ; Yunli LAI ; Lu TANG ; Shengli LI
Chinese Journal of Ultrasonography 2020;29(1):52-59
		                        		
		                        			 Objective:
		                        			To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester.
		                        		
		                        			Methods:
		                        			Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13+ 6 weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared.
		                        		
		                        			Results:
		                        			The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus.
		                        		
		                        			Conclusions
		                        			In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester. 
		                        		
		                        		
		                        		
		                        	
7.Efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria: a meta-analysis
Yunting LIANG ; Xiangyang SU ; Rongbiao LU ; Fang HUANG ; Yue ZHENG ; Wei LAI ; Chun LU
Chinese Journal of Dermatology 2018;51(6):472-475
		                        		
		                        			
		                        			Objective To evaluate the efficacy and safety of omalizumab on the treatment of chronic spontaneous urticaria (CSU) by systemic review and meta-analysis.Methods Electronic databases,such as PubMed,Clinicaltrials.gov,the Cochrane Database of Systematic Reviews,and the Cochrane Central Register of Controlled Trials,were searched to collect randomized controlled trials (RCTs) about the efficacy and safety of omalizumab in the treatment of CSU.Two reviewers independently screened RCTs according to the inclusion and exclusion criteria,extracted data,and assessed the quality of the included RCTs.And then,a meta-analysis was carried out by using RevMan 5.3 software for comparisons of the efficacy and safety of the 75-,150-,300-,600-mg omalizumab groups versus the placebo group after 1-month treatment,as well as the total omalizumab group versus the placebo group.Results A total of 7 RCTs involving 1 365 patients were included in this meta-analysis.The results showed that the total omalizumab group and different omalizumab subgroups were superior in improving the urticaria activity score of 7 days (UAS7) and wheal number score of 7 days to the placebo group (all P < 0.05).For the improvement in the itch severity score (ISS) of 7 days and complete response rate for main symptoms (UAS7 =0),the total omalizumab group,75-,150-and 300-mg omalizumab groups were superior to the placebo group (all P < 0.05),but there were no significant differences between the 600-mg omalizumab group and the placebo group (P =0.07).The dermatology life quality index (DLQI) was better in the total omalizumab group,150-and 300-mg omalizumab groups than in the placebo group (all P < 0.05),but no significant difference was observed between the 75-mg omalizumab group and the placebo group (P =0.50).There were no significant differences in the incidence of common adverse events or serious adverse events between the total omalizumab group as well as the 75-,150-and 300-mg omalizumab subgroups and the placebo subgroup (all P > 0.05).Conclusions Omalizumab can improve clinical symptoms and life quality of patients with CSU,and is effective in improving the UAS,ISS,wheal number score,DLQI and complete response rate for main symptoms (UAS =0) with high safety.Subcutaneous injection of omalizumab at a dose of 150 or 300 mg/month shows the best efficacy in improving the clinical symptoms and life quality of patients with CSU.
		                        		
		                        		
		                        		
		                        	
8.The role and clinical significance of αB-Crystallin in the proliferation and migration of non-small cell lung cancer
Jie GU ; Feng-Kai XU ; Qiao-Liang ZHU ; Lin WANG ; Di GE ; Chun-Lai LU
Fudan University Journal of Medical Sciences 2018;45(3):323-329
		                        		
		                        			
		                        			Objective To investigate the expression of αB-Crystallin in non-small cell lung cancer and adjacent tissues (NSCLC) and analyze the associations between its expression and clinicopathological features as well as proliferation and migration of NSCLC cells.Methods We down-regulated the expression of αB-Crystallin in NSCLC cell line A549 with specific siRNA,and assessed the role of αB-Crystallin in the proliferation and migration of NSCLC cell line with CCK-8 and Transwell.Then,we examined αB-Crystallin expression by immunohistochemistry (IHC) in tissue microarray (TMA) consisting of 208 cases of NSCLC who were treated in the Department of Thoracic Surgery,Zhongshan Hospital in 2005.Associations between αB-Crystallin expression and clinical characteristics were assessed and the prognostic role of αB-Crystallin in NSCLC was evaluated by Kaplan-Meier and Cox regression analysis.Results Loss of αB-Crystallin expression suppressed the proliferation and migration potential of A549 cells (P<0.05).Furthermore,immunohistochemistry in tissue microarray revealed that αB-Crystallin was overexpressed in NSCLC compared with adjacent normal tissues,αB-Crystallin expression was associated with lymph node metastasis (P < 0.05).Multivariate analysis indicated that αB-Crystallin expression was an independent prognostic factor in patients' overall survival.Conclusions Our finding indicated that αB-Crystallin was overexpressed in NSCLC and promotes proliferation and migration of NSCLC cells.Its expression was associated with poor prognosis of NSCLC patients.αB-Crystallin may represent a potential therapeutic target and a novel prognostic marker of NSCLC.
		                        		
		                        		
		                        		
		                        	
9.Cell suspension examination versus histopathological technique in detecting sperm in the testis tissue of non-obstructive azoospermia patients undergoing testicular sperm aspiration.
Liang SHI ; Jie YU ; Lai-Qing ZHU ; Xue ZHOU ; Xun WANG ; Guo-Hai SUN ; Chun-Hua ZHANG
National Journal of Andrology 2018;24(7):622-626
ObjectiveTo explore the clinical selection and application of cell suspension examination (CSE) or histopathological technique (HPT) in detecting sperm in the testis tissue obtained by testicular sperm aspiration (TESA) in patients with non-obstructive azoospermia (NOA).
METHODSTotally, 1 006 NOA patients underwent TESA and their testis tissues were subjected to CSE or HPT for sperm detection. Based on the results of CSE, the testicular tissue samples were divided into groups A (with sperm, n = 567) and B (without sperm, n = 439) and the results were compared with those of HPT.
RESULTSHPT showed 508 cases with but 59 without sperm in group A, and 403 with and 36 without sperm in group B. The consistency rate of CSE with that of HPT was 90.56% (Kappa =0.809), and CSE exhibited a significantly higher rate of sperm detection than HPT (56.36% vs 54.08%, P=0.023).
CONCLUSIONSCSE combined with HPT for detecting sperm in the testis tissue of NOA patients undergoing diagnostic TESA helps clinical diagnosis and treatment. The results of CSE have a decisive significance for assisted reproductive therapy, while those of HPT may provide some definite etiological evidence for drug therapy or surgery.
Azoospermia ; Humans ; Male ; Reproductive Techniques, Assisted ; Sperm Retrieval ; Spermatozoa ; Suspensions ; Testis
10.Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats.
Chun Lai LIANG ; Qian XIANG ; Wen Ming CUI ; Jin FANG ; Na Na SUN ; Xiao Peng ZHANG ; Yong Ning LI ; Hui YANG ; Zhou YU ; Xu Dong JIA
Biomedical and Environmental Sciences 2018;31(3):197-207
OBJECTIVETo investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes.
METHODSSprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined.
RESULTSThere were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups.
CONCLUSIONOur study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.
Administration, Oral ; Animals ; Dose-Response Relationship, Drug ; Female ; Male ; Nanoparticles ; toxicity ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity ; Toxicity Tests, Subchronic
            
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