1.Comprehensive evaluation of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy in obese patients based on efficacy and nutrition
Lifu HU ; Lun WANG ; Shixing LI ; Yang LIU ; Zheng ZHANG ; Minghao XIAO ; Zhenhua ZHANG ; Zhiqiang WEI ; Liang CUI ; Tao JIANG
Chinese Journal of Gastrointestinal Surgery 2024;27(9):945-952
Objective:To evaluate the 1-year postoperative efficacy and nutritional indicators of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in obese patients.Methods:This retrospective observational study included patients with a body mass index (BMI) of ≥40.0 kg/m 2 regardless of other related metabolic diseases and patients with severe type 2 diabetes and a BMI between 27.5 and 40.0 kg/m 2. The clinical data of 66 obese patients who underwent SADI-S at the Bariatric and Metabolic Surgery Department of China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were collected, including 53 cases of da Vinci robotic surgery and 13 cases of laparoscopic surgery. The patients comprised 38 men and 28 women with a median age of 35 (18–61) years and a mean preoperative BMI of 42.93 ± 6.82 kg/m 2. A total of 38 patients had type 2 diabetes, and 46 had hyperuricemia, 45 had hypertension, 35 had hyperlipidemia, 12 had hypercholesterolemia, and 12 had a high low-density lipoprotein (LDL) level. The main observation indicators were (1) intraoperative and postoperative conditions; (2) weight loss outcomes, including body weight, BMI, excess body weight loss (%EWL), and total body weight loss (%TWL) at 3, 6, and 12 months after surgery; (3) effects of treatment on metabolic disease; and (4) changes in nutrient indicators. Results:(1) Intraoperative and postoperative conditions: All patients successfully underwent SADI-S with neither conversion to laparotomy nor death. Four (6.1%) patients developed postoperative complications, and all of them recovered and were discharged after conservative or surgical treatment. (2) Weight loss outcomes: %EWL at 3, 6, and 12 months after surgery was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65, respectively, and %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89, respectively. Body weight and BMI 3 to 12 months after surgery were significantly lower than those before surgery (all P < 0.001). (3) Effect of treatment on metabolic disease: 3 to 12 months after surgery, fasting blood sugar, HbA1c, uric acid, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, LDL, and other indicators were significantly lower than those before surgery (all P < 0.05). Twelve months after surgery, the remission rates of diabetes, hyperuricemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and high LDL were 100% (38/38), 65.2% (30/46), 62.2% (28/45), 94.3% (33/35), 100% (12/12), and 100% (12/12), respectively. (4) Changes in nutrient indicators: Compared with the preoperative nutrient levels, the hemoglobin and hematocrit levels were lower at 3 to 12 months after surgery, the total protein level was lower at 6 to 12 months after surgery, the albumin level was lower at 6 months after surgery, and the ferritin level was lower at 3 months after surgery. The differences were statistically significant (all P < 0.05). The incidence of anemia was 6.1% (4/66), hypoalbuminemia was 4.5% (3/66), and ferritin deficiency was 4.5% (3/66), all of which were improved or normalized through conservative treatment. Twelve months after surgery, 30 (45.5%) patients had vitamin A deficiency, 17 (25.8%) had vitamin E deficiency, 11 (16.7%) had folic acid deficiency, 2 had potassium deficiency (3.0%), 3 (4.5%) had calcium deficiency, 2 (3.0%) had magnesium deficiency, 9 (13.6%) had iron deficiency, and 16 (24.2%) had zinc deficiency. However, no relevant clinical symptoms occurred. Conclusions:SADI-S has a very significant effect on weight loss and alleviation of metabolic diseases. Nutrient deficiencies after SADI-S mainly involve vitamin A, vitamin E, zinc, and folic acid. The long-term efficacy and safety of SADI-S still need further follow-up observation.
2.Comprehensive evaluation of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy in obese patients based on efficacy and nutrition
Lifu HU ; Lun WANG ; Shixing LI ; Yang LIU ; Zheng ZHANG ; Minghao XIAO ; Zhenhua ZHANG ; Zhiqiang WEI ; Liang CUI ; Tao JIANG
Chinese Journal of Gastrointestinal Surgery 2024;27(9):945-952
Objective:To evaluate the 1-year postoperative efficacy and nutritional indicators of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) in obese patients.Methods:This retrospective observational study included patients with a body mass index (BMI) of ≥40.0 kg/m 2 regardless of other related metabolic diseases and patients with severe type 2 diabetes and a BMI between 27.5 and 40.0 kg/m 2. The clinical data of 66 obese patients who underwent SADI-S at the Bariatric and Metabolic Surgery Department of China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were collected, including 53 cases of da Vinci robotic surgery and 13 cases of laparoscopic surgery. The patients comprised 38 men and 28 women with a median age of 35 (18–61) years and a mean preoperative BMI of 42.93 ± 6.82 kg/m 2. A total of 38 patients had type 2 diabetes, and 46 had hyperuricemia, 45 had hypertension, 35 had hyperlipidemia, 12 had hypercholesterolemia, and 12 had a high low-density lipoprotein (LDL) level. The main observation indicators were (1) intraoperative and postoperative conditions; (2) weight loss outcomes, including body weight, BMI, excess body weight loss (%EWL), and total body weight loss (%TWL) at 3, 6, and 12 months after surgery; (3) effects of treatment on metabolic disease; and (4) changes in nutrient indicators. Results:(1) Intraoperative and postoperative conditions: All patients successfully underwent SADI-S with neither conversion to laparotomy nor death. Four (6.1%) patients developed postoperative complications, and all of them recovered and were discharged after conservative or surgical treatment. (2) Weight loss outcomes: %EWL at 3, 6, and 12 months after surgery was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65, respectively, and %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89, respectively. Body weight and BMI 3 to 12 months after surgery were significantly lower than those before surgery (all P < 0.001). (3) Effect of treatment on metabolic disease: 3 to 12 months after surgery, fasting blood sugar, HbA1c, uric acid, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, LDL, and other indicators were significantly lower than those before surgery (all P < 0.05). Twelve months after surgery, the remission rates of diabetes, hyperuricemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and high LDL were 100% (38/38), 65.2% (30/46), 62.2% (28/45), 94.3% (33/35), 100% (12/12), and 100% (12/12), respectively. (4) Changes in nutrient indicators: Compared with the preoperative nutrient levels, the hemoglobin and hematocrit levels were lower at 3 to 12 months after surgery, the total protein level was lower at 6 to 12 months after surgery, the albumin level was lower at 6 months after surgery, and the ferritin level was lower at 3 months after surgery. The differences were statistically significant (all P < 0.05). The incidence of anemia was 6.1% (4/66), hypoalbuminemia was 4.5% (3/66), and ferritin deficiency was 4.5% (3/66), all of which were improved or normalized through conservative treatment. Twelve months after surgery, 30 (45.5%) patients had vitamin A deficiency, 17 (25.8%) had vitamin E deficiency, 11 (16.7%) had folic acid deficiency, 2 had potassium deficiency (3.0%), 3 (4.5%) had calcium deficiency, 2 (3.0%) had magnesium deficiency, 9 (13.6%) had iron deficiency, and 16 (24.2%) had zinc deficiency. However, no relevant clinical symptoms occurred. Conclusions:SADI-S has a very significant effect on weight loss and alleviation of metabolic diseases. Nutrient deficiencies after SADI-S mainly involve vitamin A, vitamin E, zinc, and folic acid. The long-term efficacy and safety of SADI-S still need further follow-up observation.
3.Association between early-life factors and pubertal timing in girls.
Ding ZENG ; Jian-Ping LIANG ; Yi-Jin ZHENG ; Na-Li DENG ; Lun YANG ; Shuang LU ; Yi YANG ; Li LIU
Chinese Journal of Contemporary Pediatrics 2023;25(2):153-158
OBJECTIVES:
To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls.
METHODS:
The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing.
RESULTS:
A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing.
CONCLUSIONS
High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.
Female
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Humans
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Birth Weight
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Body Mass Index
;
China
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Gestational Age
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Logistic Models
;
Puberty, Precocious
4.Interpretation and consideration of “Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” in General Texts of European Pharmacopoeia
Xuan-xuan ZHANG ; Xing WU ; Qun-ying MAO ; Miao XU ; Zheng-lun LIANG
Chinese Journal of Biologicals 2023;36(1):1-4+10
Interpretation and consideration of “Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” in General Texts of European Pharmacopoeia
Potency is a critical quality attribute for controlling relevant biological properties and batch consistency of vaccines.The methods can be divided into in vivo and in vitro methods according to whether animals are used.The in vivo methods are large consuming of animals and time,as well as have large variant detection results.In contrast,the in vitro alternative methods have been the hotspot of research due to their simple operations,in line with 3Rs principles,and more stable results.However,owing to the complexity of experimental design and the lack of corresponding guidance,the research progress of alternative methods is slow.Recently,“Substitution of in vivo method(s) by in vitro method(s) for the quality control of vaccines” was adopted in the European Pharmacopoeia(10th Edition),which clarifies the critical points of consideration for substitution.This paper interprets the chapter and puts forward some thoughts on that in China,which is expected to speed up the alternative methods research and improve the ability of vaccine quality control and supervision in China.
5.Association analysis between extracurricular physical activity and dyslipidemia among primary, middle and high school students in Guangzhou.
Wan Wen YAO ; Jian Ping LIANG ; Wei Qing TAN ; Lun YANG ; Shuang LU ; Wei Hao HUANG ; Chao CHEN ; Yi Jin ZHENG ; Yi YANG ; Li LIU
Chinese Journal of Cardiology 2021;49(7):708-713
Objective: To investigate the prevalence of dyslipidemia, and to explore the association between extracurricular physical activity and dyslipidemia among primary, middle and high school students in Guangzhou. Methods: This cross-sectional study selected primary and middle school students in Guangzhou by the stratified cluster sampling method from March to December 2019. Physical examination and blood lipid test were performed. Information about students' basic characteristics and extracurricular physical activity was collected by questionnaire. Multivariate logistic regression analysis was used to determine the association between extracurricular physical activity and dyslipidemia in this cohort. Results: A total of 7 797 participants (mean aged (12.2±2.9) years) were included (4 194 (53.79%) boys and 3 603 (46.21%) girls]. The detection rates of high total cholesterol, high triglycerides, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and dyslipidemia were 12.49% (974/7 797), 6.44% (502/7 797), 6.62% (516/7 797), 11.31% (882/7 797) and 23.83% (1 858/7 797), respectively. Dyslipidemia rate was lower in the junior school students (21.39% (675/3 156)) than in primary school students (25.96% (896/3 451)) and high-school students (24.12% (287/1 190)) (P<0.001). The dyslipidemia rates of boys and girls were similar (23.15% (971/4 194) vs. 24.62% (887/3 603), P>0.05). Dyslipidemia rate was lower in students with extracurricular physical activity than in students without extracurricular physical activity (22.50% (923/4 102) vs. 25.30% (935/3 695), P<0.05). Multivariate logistic regression analysis showed that extracurricular physical activity was associated with lower risk of dyslipidemia (OR=0.88, 95%CI=0.79-0.99, P=0.033). Among all types of extracurricular physical activities, participating in extracurricular large ball game was associated with 28% lower risk among junior school students (OR=0.72, 95%CI=0.57-0.91, P=0.006). Conclusion: The prevalence of dyslipidemia is high among primary, middle and high school students in Guangzhou. Extracurricular physical activity is associated with reduced risk of dyslipidemia in this cohort.
6.Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma.
Hao DUAN ; Ji-Long HU ; Zheng-He CHEN ; Jue-Hui LI ; Zhen-Qiang HE ; Zhen-Ning WANG ; Guan-Hua ZHANG ; Xiao-Yu GUO ; Lun LIANG ; Yong-Gao MOU
Chinese Medical Journal 2020;133(12):1415-1421
BACKGROUND:
Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.
METHODS:
CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.
RESULTS:
Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.
CONCLUSION
Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.
7.Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease.
Dong-Liang FU ; Ting-Ting ZHAO ; Wen-Hua PENG ; Peng YANG ; Xiao-Fei LIU ; Hu ZHANG ; Xian-Lun LI ; Yong WANG ; Jin-Gang ZHENG ; Yan-Xiang GAO ; Hong-Kai LU ; Qi WANG
Chinese Medical Journal 2017;130(16):1914-1918
BACKGROUNDCoronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease.
METHODSThis study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation.
RESULTSThe mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel.
CONCLUSIONDialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.
8.Survey on prevalence of occupational musculoskeletal disorders among workers in a shipyard.
Lei XU ; Zheng-lun WANG ; Ting-bo SONG ; Xue-bin ZHAO ; Lei WU ; Biao CHEN ; Liang PENG ; Li-hua HE ; Sheng WANG ; Lei YANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2011;29(3):180-183
OBJECTIVETo study the prevalence of occupational musculoskeletal disorders (OMSDs) in a shipyard and explore the relationship between type of work, age, length of service and OMSDs by cross sectional epidemiological survey.
METHODS1570 workers from a shipyard were selected as survey objects, and a revised Northern Europe Standardized Questionnaire was used to investigate OMSDs. 253 technicians and clerks in the shipyard were selected as controls.
RESULTSOMSDs in these workers primarily located in waist, neck and shoulder, prevalence were 58.0%, 54.6% and 44.3% respectively; There were significant differences among workers of different types of work (P < 0.05) in prevalence and the cumulative parts number of OMSDs. The control group in this study also showed a higher prevalence of neck, shoulder and waist OMSDs. Female workers had higher prevalence of OMSDs in neck and shoulder compared with male workers (P < 0.05). As well there was significant correlation between age and OMSDs prevalence except the wrist and ankle disorders (P < 0.05), OMSDs prevalence increased with years. In addition, there was correlation between length of service and OMSDs prevalence, the group of ≤ 5 years had the lowest prevalence and the prevalence of low-back, neck and shoulder increased with service years.
CONCLUSIONThe OMSDs in workers engaged in shipyard are serious, the length of service, age, gender and type of work seem to be the risk factors, and it seems reasonable that the ergonomics intervention in the above aspects should be necessary for the prevention of OMSDs.
Adolescent ; Adult ; Female ; Humans ; Industry ; Male ; Middle Aged ; Musculoskeletal Diseases ; epidemiology ; Occupational Diseases ; epidemiology ; Prevalence ; Ships ; Surveys and Questionnaires ; Young Adult
9.Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants.
Qun-Ying MAO ; Xue-Yan LIAO ; Xiang YU ; Nan LI ; Feng-Cai ZHU ; Ying ZENG ; Zheng-Lun LIANG ; Feng-Xiang LI ; Jun-Zhi WANG ; Feng-Min LU ; Hui ZHUANG
Chinese Medical Journal 2010;123(13):1679-1684
BACKGROUNDEnterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently.
THE AIMS OF OUR STUDY WEREto explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.
METHODSPeripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.
RESULTSSeropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P < 0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.
CONCLUSIONSThe prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.
Antibodies, Neutralizing ; blood ; immunology ; Cells, Cultured ; Enterovirus ; immunology ; Enterovirus A, Human ; immunology ; Female ; Hand, Foot and Mouth Disease ; immunology ; virology ; Humans ; Infant ; Infant, Newborn
10.Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway.
Yan-Xia YU ; Zhen-Lun GU ; Jiang-Lin YIN ; Wen-Hsien CHOU ; Chi-Yi KWOK ; Zheng-Hong QIN ; Zhong-Qin LIANG
Chinese Medical Journal 2010;123(14):1915-1923
BACKGROUNDUrsolic acid (UA) is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721.
METHODSAfter treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 micromol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting.
RESULTSThe proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-alpha.
CONCLUSIONActivation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.
Apoptosis ; drug effects ; Blotting, Western ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Flow Cytometry ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; Microscopy, Electron, Transmission ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Triterpenes ; therapeutic use ; Tumor Suppressor Protein p53 ; metabolism


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