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Objectives To develop a multi-stage and multi-epitope vaccine, which consists of epitopes from the early secretory and latency-associated antigens of Mycobacterium tuberculosis (MTB). Methods The B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes of 12 proteins were predicted using an immunoinformatics. The epitopes with antigenicity, without cytotoxicity and sensitization, were further screened to construct the multi-epitope vaccine. Furthermore, the proposed vaccine underwent physicochemical properties analysis and secondary structure prediction as well as 3D structure modeling, refinement and validation. Then the refined model was docked with TLR4. Finally, an immune simulation of the vaccine was carried out. Results The proposed vaccine, which consists of 12 B-cell, 11 CTL and 12 HTL epitopes, had a flexible and stable globular conformation as well as a thermostable and hydrophilic structure. A stable interaction of the vaccine with TLR4 was confirmed by molecular docking. The efficiency of the candidate vaccine to trigger effective cellular and humoral immune responses was assessed by immune simulation. Conclusion A multi-stage multi-epitope MTB vaccine construction strategy based on immunoinformatics is proposed, which is expected to prevent both active and latent MTB infection.
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Mycobacterium tuberculosis/metabolism , Molecular Docking Simulation , Toll-Like Receptor 4 , Epitopes, T-Lymphocyte/chemistry , Epitopes, B-Lymphocyte/chemistry , Vaccines, Subunit/chemistry , Computational Biology/methodsABSTRACT
Objective:To study the pathogenic distribution of bronchoalveolar lavage fluid in children with severe pneumonia from Children′s Hospital Affiliated to Soochow University, and to investigate the drug resistance of major pathogenic bacteria.Methods:A total of 177 children with severe pneumonia undergoing fiberoptic bronchoscopy in Children′s Hospital Affiliated to Soochow University from January 2014 to December 2018 were enrolled.Their bronchoalveolar lavage fluid was collected for pathogen identification, pathogen culture and drug sensitivity analysis.The pathogens were detected by direct immunofluorescence quantitative PCR.Results:Of 177 cases enrolled, 100 children had at least one pathogen detected, and the positive rate was 58.13%.Among all the pathogens detected, Mycoplasma pneumonia (MP) had the highest detection rate, which was found in 41 cases.The top three bacteria detected included Streptococcus pneumoniae (9 cases, 10.59%), Staphylococcus aureus (8 cases, 9.41%), and Pseudomonas aeruginosa (6 cases, 7.06%). The top three viruses detected were cytomegalo virus (CMV) (14 cases, 33.33%), human bocavirus (HBoV) (10 cases, 23.81%), and respiratory syncytial virus (RSV) (8 cases, 19.05%). The drug sensitive test indicated that main kinds of Gram-negative bacteria had low resistance to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Main kinds of Gram-positive bacteria had low resistance to Linezolid and vancomycin.The virus detection rate and MP detection rate in severe pneumonia children under 5 years old were about 30.00% and 20.00%, respectively.The MP detection rate in children above 5 years old exceeded 30.00%.The bacteria detection rates in children under and above 2 years old were over 20.00% and about 15.00%, respectively.Airway abnormalities were common in children with severe pneumonia, mainly including tracheobronchial malacia and stenosis. Conclusions:The most common pathogen of bronchoalveolar lavage fluid in severe pneumonia children under 5 years old in Suzhou is viruses.The bacteria detection rate is high in children under 2 years old.Common Gram-positive bacteria show high susceptibility to vancomycin and Linezolid. Pseudomonas aeruginosa is highly sensitive to quinolones, aminoglycosides, carbapenems, and enzymatic beta-lactams.Importance should be attached to the airway abnormalities in children, especially infants, with severe pneumonia.
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Objective:To investigate the relationship between angiopoietin-like protein 4(ANGPTL4) and vascular endothelial growth factor(VEGF) in serum and lower limb arterial lesions in Type 2 diabetes mellitus.Methods:Using the method of retrospective cohort study, 164 inpatients with type 2 diabetes admitted to the Department of Endocrinology, Dahua hospital, Xuhui District, Shanghai from October 2017 to December 2018 were selected as the type 2 diabetes group, and 69 healthy people in the same period were collected as the normal control group.According to the ankle brachial index<0.9, diabetic patients were divided into two groups: the group without lower extremity artery disease and the group with lower extremity artery disease.The levels of ANGPTL4 and VEGF in serum were measured by enzyme-linked immunosorbent assay.Results:(1)Compared with the normal control group: the concentration of ANGPTL4 in serum of lower extremity arterial disease group and no lower extremity arterial disease group((44.78±15.15), (47.46±10.43) μg/L) were lower than that of normal control group((52.87±12.74) μg/L), the difference was statistically significant (all P<0.05). The serum VEGF concentration in lower extremity arterial disease group and no lower extremity arterial disease group((340.98±76.18), (314.83±75.30) ng/L) were higher than that in normal control group((282.58±81.4) ng/L), the difference was statistically significant(all P<0.05). (2)Compared with no lower extremity arterial disease group: the concentration of ANGPTL4 in serum of lower extremity arterial disease group was lower than that of no lower extremity arterial disease group, but the difference was not statistically significant( P>0.05). The serum VEGF concentration in lower extremity arterial disease group was higher than that in no lower extremity arterial disease group, the difference was statistically significant( P<0.05). (3)Correlation analysis: Diabetes mellitus and diabetic course>10 years( OR 4.594, 95% CI2.540-8.311, P<0.001), fasting blood glucose>8 mmol/L( OR 2.353, 95% CI1.023-5.416, P=0.044), glycosylated hemoglobin>8%( OR 6.442, 95% CI 2.874-14.441, P<0.001) and the increase of VEGF( OR 3.745, 95% CI1.566-8.953, P=0.003) are risk factors for lower limb arterial disease in type 2 diabetes, while the increase of ANGPTL( OR 0.154, 95% CI0.064-0.372, P<0.001) can reduce the occurrence of lower limb arterial disease in type 2 diabetes. Conclusion:ANGPTL4 is a protective factor and VEGF is a risk factor of type 2 diabetes mellitus.Both of them influence each other and participate in its occurrence and development.
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Aromatase inhibitors (AIs) directly applies to postmenopausal breast cancer patients. Patients underwent bilateral ovariectomy or ≥60 years were acknowledged as postmenopausal.Alternatively, for <60 years breast cancer patients, sex hormone detection to evaluate menopause is recommended by National Comprehensive Cancer Network (NCCN) guideline, textbooks, and AIs clinical trials.However, series of clinical trial found that, a broad overlap region of follicle stimulating hormone and estradiol appeared between premenopausal and postmenopausal patients, which unable to determine the menopause even with sensitivity promotion of detection equipment or manners.We have abandon this detection in clinical treatment, and decision making was only according to the relapse risk and disease status. We recommend bilateral ovariectomy resection accompanied with AIs for breast cancer patients with high recurrence risk (e.g. T3-4 or LNM≥4) or patients with advanced metastatic disease.However, patients with low or moderate recurrence risk can be treated with tamoxifen.
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Osteoblastic metastasis of breast cancer is relatively rare, but there are cases of misdiagnosis and mistreatment in clinical treatment. They can only be diagnosed by X ray or CT bone scan and must be identified from bone repair after effective treatment in patients with osteolytic or mixed bone metastases. Bone metastasis is often seen in the disease-free condition of breast cancer, and very few can occur in stage Ⅳ lesions prior to surgery. Based on the analysis of clinical phenomena, we questioned the evaluation criteria of the therapeutic effect on bone metastasis of breast cancer created by the World Health Organization and the MD Anderson Cancer Center and concluded the formation mechanism of bone metastasis. For patients with simple osteoblastic bone metastasis, we broke through the recommendations of the National Comprehensive Cancer Network guideline and advocated the concept of "noninterference" . Patients with positive hormone receptor can be treated with traditional endocrine therapy. Hormone receptor negative and/or human epidermal growth factor receptor 2 positive patients can be observed first, followed by chemotherapy and/or targeted therapy when there is osteolytic bone metastasis or visceral metastasis. Furthermore, bisphosphonates are not required since osteoblastic bone metastasis is generally not associated with the risk of bone related events. The active treatment of primary lesion should be taken into account in stage Ⅳ patient before operation.
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Objective To explore the effect of prognosis of consolidation radiotherapy for patients after R0 resection of local recurrence after radical mastectomy. Methods Totally 110 breast cancer patients with local recurrence receiving R0 resection were admitted and treated in our hospital from January 1st, 2003 to November 30th, 2015 were retrospectively analyzed. Results The median local progression time of 74 patients receiving consolidation radiotherapy ( 67.3％) was remarkably better than that of those without radiotherapy(36 patients, 32.7％), and the difference was statistically significant (χ2 =8. 526, P<0.05). Meanwhile, there was no statistically significant difference (P>0.05) of distance disease-free survival and overall survival between the radiotherapy group and the non-radiotherapy group. Multifactor analysis indicated that pseudo-adjuvant endocrine therapy (χ2 =7.541,95％CI:27.1％ -80.4％, P <0.05), DDFS(≥2 years vs. <2 years,χ2 =4.068,95％CI:101.4％ -267％,P<0. 05) and pseudo-adjuvant radiotherapy(χ2 =14.126, 95％CI:21.7％ -80.4％, P <0. 05 ) were the independent risk factors affecting the OS of patients with local recurrence after R0 resection. Conclusions For the patients with local recurrence after R0 resection of local recurrence, it is recommended that consolidation radiotherapy should be done and the radiation field should include the same side of the chest wall and clavicle area lymphatic drainage area.
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Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.
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Objective To explore the risk factors for childhood death from pneumococcal meningitis.Methods The data of 32 hospitalized children were retrospectively analyzed,who were diagnosed as pneumococcal meningitis and enrolled in the Affiliated Children′s Hospital of Soochow University from November 201 0 to December 201 5.The subjects were divided into the death group and survival group according to their prognosis.The clinical characteristics and laboratory data were compared between 2 groups.Results Between the death group and survival group,there were significant statistically differences in shock within 24 hours after admission(63.6% vs 1 4.3%,P =0.01 3),as well as endotracheal tube intubation(1 00.0% vs 23.8%,P <0.001 ),the levels of cerebrospinal fluid(CSF)IgG[(491 .27 ± 203.53)mg/L vs (267.24 ±1 88.07)mg/L,P =0.006],IgM[(1 1 5.72 ±79.1 9)mg/L vs (32.80 ±28.52)mg/L, P =0.006],IgA[59.52(1 5.51 ,75.69)mg/L vs 1 8.77(9.33,27.54)mg/L,P =0.023],CSF leukocyte[330.00 (1 50.00,380.00)×1 06 /L vs 870.00 (403.00,6 1 60.00)×1 06 /L,P =0.009 ],CSF protein [(4 047.00 ± 1 942.1 6)mg/L vs (2 470.62 ±1 259.94)mg/L,P =0.009],CSF adenosine deaminase (ADA)[35.20(1 8.90, 87.20)U /L vs 8.80(3.05,23.78)U /L,P =0.001 ],serum sodium[(1 30.21 ±2.85)mmol/L vs (1 32.83 ±3.69) mmol/L,P =0.049],serum lactic acid (LA)[4.40 (2.60,5.70)mmol/L vs 2.40 (1 .75,4.50)mmol/L,P =0.01 3],serum C -reactive protein (CRP)[(95.87 ±65.40)mg/L vs (1 65.61 ±83.05)mg/L,P =0.022],serum lactate dehydrogenase (LDH)[81 3.40(465.20,2 31 0.70)U /L vs 359.20(257.85,405.90)U /L,P =0.001 ], platelet[(1 63.82 ±1 64.86)×1 09 /L vs (295.71 ±1 30.29)×1 09 /L,P =0.01 9]and positive rate of blood culture (90.9% vs 47.6%,P =0.023)between the death group and survival group.Conclusions The risk factors associated with mortality in pediatric SPM include shock within 24 hours after admission,endotracheal intubation,hyponatremia, thrombocytopenia,as well as high serum LA level,high serum LDH level,lower serum CRP level or cultures of blood and CSF double positive.
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ObjectiveTo investigate the clinical features and prognosis of children with rotavirus gastroenteritis and convulsion.MethodsClinical data of children with rotavirus gastroenteritis hospitalized from January 2010 to December 2013 were retrospectively analyzed. Subjects were divided into the seizure group and no seizure group according to the presence of seizure in the course and compared between the two groups.ResultsThere were no signiifcant differences in sex, age, and the average duration of hospitalization between two groups (allP>0.05). The family history, history of seizures, the levels of serum sodium, calcium, lactate, standard bicarbonate concentration (SB), actual bicarbonate concentration (AB), carbon dioxide content (TCO2) and pH were statistically signiifcant between two groups (allP>0.05). During the follow-up period (outpatient telephone follow-up), the recurrence of seizure in two groups was signiifcant different (P<0.05) and only one (0.54%) child in seizure group developed epilepsy.ConclusionThis study showed that rotavirus gastroenteritis with convulsion is a benign clinical course.
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Objective To develop an early diagnosis strategy for radiation-associated breast angiosarcoma after breast cancer radiotherapy (RABASBCR) and to avoid the misdiagnosis of this disease.Methods A systematic search of PubMed for published reports of RABASBCR cases was performed.The clinical manifestations and radiological features in the early stage of disease,as well as biopsies,were analyzed to screen out valuable markers for early diagnosis and develop the early diagnosis strategy for RABASBCR.Results Fifty-five original articles involving 80 RABASBCR patients were selected for this analysis.Twenty-four (30％) of the 80 patients were misdiagnosed;the median time of misdiagnosis was 3 months (1-24 months).The earliest symptom was skin changes in 76 (95％) of the 80 patients.The misdiagnosis rates of ultrasound,mammography,computed tomography,and magnetic resonance imaging for RABASBCR were 9/9,31/32,2/2,and 1/5,respectively.The misdiagnosis rates of fine needle biopsy,core needle biopsy,and incisional biopsy were 7/14,12/25,and 10/26,respectively.Conclusions By analyzing published case reports,we have set up the early diagnosis strategy for RABASBCR with reference to the Cahan criteria.
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Objective To analysis the influence factors of standardization in the hierarchical chain management of type 2 diabetes and to enhance the hierarchical chain management of type 2 diabetes.Methods ( 1 ) Six hundred and ninty patients with type 2 diabetes completed 1 years management were divided into well-controlled glycosylated hemoglobin ( HbAlc ) group (＜7.0％ ) and bad-controlled glycosylated hemoglobin (HbAlc) group ( ≥ 7.0％ ).The conditions of diet,physical activity,medication,self-blood sugar monitoring and participation in health seminars were investigated and analyzed.(2) The patients were divided into standardized management group and not standardized management group.Their age,sex,educational background,occupation,monthly income per person,medical security,the course,cognition for glycuresis,two-way transfer,and chronic complications were investigated and statistically analyzed.Results ( 1 ) The proportions of physical activity (70.1％ vs 54.2％,x2=6.163,P=0.018),self-blood sugar monitoring(60.4％ vs 43.8％,x2=6.268,P=0.016) and participation in health seminars (56.0％ vs 41.7％,x2=4.577,P=0.045) in the well-controlled HbAlc group were significantly higher than those in the bad-controlled HbAlc group.(2) Their age [(61.08 ±10.04) years old vs ( 57.75 ± 9.89 ) years old,t=2.539,P=0.012],educational background ( ratio of low educational attainment:8.3 ％ vs 17.2％,x2=6.426,P=0.041 ),medical security (own expense ratios:4.6％ vs 11.5％,x2=3.543,P=0.048 ),awareness of diabetes ( ratio of poor awareness of diabetes:19.4％ vs 41.0％,x2=17.518,P=0.000 ),two-way transfer ( ratio of not transfer treatment:4.6％ vs 14.8％,x2=7.662,P=0.022) and chronic complications ( ratio of chronic complication:41.7 ％ vs 26.2％,x2=6.130,P=0.017) were significantly different between the standardized management group and not standardized management group.(3) Logistic regression analyses indicated that the age ( OR=0.954,P=0.006),monthly income per person ( OR=4.101,P=0.018 ),medical security ( OR=7.617,P=0.003 ),cognition for glycuresis ( OR=0.030,P=0.000),two-way transfer ( OR=9.079,P=0.000) and chronic complications ( OR=0.456,P=0.031 ) were the risk factors of standardized management.Conclusion We should focus on the impact factors affecting the standardized management of patients including age,monthly income per person,medical security,awareness of diabetes,ratio of not transfer treatment,positive strategies for chronic complications,improve the hierarchical chain management of type 2 diabetes,and then make the diabetic patients to early participate in standardization management of diabetes mellitus and delay the appearance of complications.
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Objective To investigate the relationship of homocysteine and blood glucose wavy coefficient with type 2 diabetic nephropathy.Methods Glycosylated hemoglobin A1c (HbA1c),fasting blood glucose(FBG),fasting C-peptide,homocysteine(Hcy),blood-fat and 24h urinary albumin quantitative (UAlb) of 154 patients with type 2 diabetes were determined,and the blood glucose wavy coefficient were calculated after blood glucose monitored by a continuous glucose monitoring system (CGMS).The patients were divided into two groups according to the quantity of UAlb:high UAlb group (n =81 ) and normal UAlb group( n =73 ).Then the difference were compared between two groups and multiple regression analysis was done between UAlb and a variety factors.Results The course of disease in high UAlb group were significantly longer than that in normal UAlb group ( (9.68 ± 7.31 ) years vs ( 5.44 ± 3.65 ) years,t =3.427,P ＜ 0.05 ).There were significant difference on HbA1c [ ( 9.61 ± 2.44 ) ％ vs ( 8.69 ± 2.35 ) ％,t =2.162 ],blood glucose wavy coefficient [ ( 3.06 ± 0.85 ) vs (2.58 ± 0.91 ),t =2.437],low density lipoprotein-cholesterol (LDL-C) [ (3.46 ± 0.83 )mmol/L vs ( 3.01 ± 0.84 ) mmol/L,t =2.596 ],UAlb [ ( 129.64 ± 118.5 ) mg/24 h vs ( 18.14 ± 3.54 )mg/24 h,t =6.421 ),UA ( ( 335.02 ± 90.39 ) mmol/L vs ( 287.00 ± 92.03 ) mmol/L,t =2.541 ) and Hcy [ ( 15.55 ± 4.53 ) mmol/L vs ( 13.12 ± 4.44 ) mmol/L,t =2.603 ] between the two groups ( P ＜ 0.05 or P ＜0.01 ).Pearson analysis showed that the courses of disease,LDL-C,UA,Hcy and blood glucose wavy coefficient were positively correlated with UAlb ( r =0.363,0.270,0.220,0.252,0.236 respectively ; P =0.000,0.008,0.033,0.014,0.022,respectively).And the multiple regression analysis indicated that UAlb was related with courses of disease(β =0.344,P =0.000),Hcy(β =0.244,P =0.011 ) and blood glucose wavy coefficient(β =0.229,P =0.012).Conclusion The elevation of serum Hcy and blood glucose wavy coefficient are risk factors to type 2 diabetic nephropathy.Lowering Hcy concentration and reducing the glucose variability may be a new way to prevent the occurrence of type 2 diabetic nephropathy.
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Objective To investigate the relationship and mechanism of the heme oxygenase-1 expression in peripheral blood mononuclear cells (PBMC) and the oxidative stress in diabetic nephropathy. Methods Two groups of diabetic patients with or without diabetic nephropathy and a normal control group were enrolled in this study. Fasting blood glucose (FBG), HbA1c, serum MDA level, ROS level, HO-1 mRNA level and HO-1 protein expression in PBMC were determined. Results In control group, diabetic group and diabetic nephropathy group , the MDA levels significantly increased[(14.23±5.07)nmol/ml vs (24.90±7.12)nmol/ml vs (43.83±16.97)nmol/ml](F＝37.022,P＜0.01), the ROS levels significantly increased (113.18±58.59 vs 364.54±88.67 vs 524.35±162.51)(F＝68.369,P＜0.01) and the HO-1 protein expression also increased significantly (22.84±9.98 vs 36.72±15.85 vs 58.1±15.93)(F＝31.302,P＜0.01). There was a positive correlation among the HO-1 mRNA, protein expression and MDA level(r＝0.407,0.429,P＜0.05). Conclusions There existed a severer oxidative stress condition in patients with diabetic nephropathy compared with the patients without diabetic nephropathy. HO-1 could be a potential pathway to ameliorate oxidative stress in diabetic kidney disease patients.
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Objective To analyze the clinic characteristics, lifetime and prognostic factors of young female breast cancer patients. MethodsClinical data of 155 patients under 35 years of age with breast cancer were retrospectively reviewed and followed up.ResultsThe positive rate of hormone receptors was 61.6 % (77/125) in all cases who had been detected receptor status. The median survival time in hormone receptors positive and negative group were 119.0 and 51.3 months (P＜0.01), and 5-year survival rates were 68 % and 33 %, respectively. For patients who had been treated with adjuvant tamoxifen (47.1%), the median survival time was 182 months which longer than without tamoxifen (P ＜0.05). The median disease-free survival time and median survival time were 24 and 91 months in all cases. The overall 3-, 5- and 10-year survival rates were 79 %, 60 % and 51%, respectively. Multifactor analysis with the COX model indicated that tumor size, axillary metastatic status, tamoxifen treatment and overexpression of Her-2 were independent prognostic factors. While clinic stage and hormone receptors status might be referenced prognostic factors. ConclusionYoung women breast cancer patient may have good prognosis if multimodality treatment is conducted. Tumor size, axillary metastatic status, adjuvant endocrine therapy and overexpression of Her-2 are independent prognostic factors.
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Aim By establishing mouse acute myocardial infarction model,to observe the protection of isoflavones on ischemic myocardium and research the mechanism.Methods Mouse acute myocardial infarction model was established by ligating the left anterior descending(LAD)coronary artery.Danshen was used as the positive control.The effect of isoflavones on myocardial infarct area,serum myocardium creatase and serum levels of SOD and MDA was observed.By Real Time PCR,it was found that isoflavones could affect the expression of β-adrenergic receptor kinase(β-ARK_1).Results Isflovones could obviously reduce the myocardial infarct area and lower the levels of serum myocardial creatase and MDA.It could downregulate the expression of β-ARK_1 as the doses are increased.Conclusions Isoflavones can protect the myocardium of acute myocardial infarction mouse.The mechanism is related to the reduction of the oxidative damage,and the downregulation of the expression of β-ARK_1.
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Thirty nine compounds in the volatile oils of the flowerbuds of Panax quinquefolium L.cultivated in China were isolated and identified with gas chromatography/mass spectre metry. To our great surprise,β-famensene,a sesquiterpene compound of them,alone account for 48.67% of the total volatile oils contents. This experimental result was contrasted with the volatile oils components of the different parts of Panax quinquefolium L.and Panax ginseng,anidentical genus plant,on chemical components and relative quantities.It was discovered that the only one common component is β-famensene in them and it is the highest value in determined relative contents. Above result provides scientific basis for biological synthesis of triterpenoid saponins.