1.Lipopolysaccharide induces aging phenotype of hematopoietic stem cells in bone marrow and spleen of young mice
Ke BAI ; Mi ZOU ; Qiang ZHAN ; Yingxin HUANG ; Zhenyu JU ; Zhiyang CHEN
Chinese Journal of Pathophysiology 2024;40(1):38-46
		                        		
		                        			
		                        			AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.
		                        		
		                        		
		                        		
		                        	
2.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
		                        		
		                        			
		                        			Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
		                        		
		                        		
		                        		
		                        	
3.Analysis of Patient-related Factors Affecting Difficulty of Colonoscopy
Xujin CHEN ; Cheng YANG ; Xianlan ZHU ; Bingni WEI ; Lin JI ; Zhujun XIE ; Feng JU ; Leyao ZHANG ; Qiang ZHAN
Chinese Journal of Gastroenterology 2023;28(8):449-455
		                        		
		                        			
		                        			Background:Complete colonoscopy is key to the diagnosis and treatment of colorectal disease,its role in reducing the morbidity and mortality of colorectal cancer is well known.Nonetheless,there are numerous factors,not just from the endoscopist's perspective but also from the patient's,that can potentially increase the difficulty of completing a colonoscopy.Aims:To identify patient-related factors that influenced the difficulty of a colonoscopy.Methods:Through two rounds of expert consultation,the factors that might affect the difficulty of colonoscopy were selected.A total of 1621 consecutive painless colonoscopies from Jan.2021 to Jan.2022 at the endoscopy center of The Affiliated Wuxi People's Hospital of Nanjing Medical University were evaluated in a retrospective manner.Factors including demographic data,cecal insertion time,adenoma detection rate and so on were recorded.These factors were analyzed to determine their association with difficulty by using Logistic regression model.Results:A total of 29 patient-related factors affecting the difficulty of colonoscopy were selected.Through retrospective analysis,the mean age of 1621 cases was(47.45±13.27)years,of which 45.8%were male and the mean body mass index was(23.32±3.11)kg/m2.Logistic regression analysis revealed that age≥60 years(OR=2.890,95%CI:1.957-4.269,P<0.001),female gender(OR=0.324,95%CI:0.217-0.484,P<0.001),history of gynecological surgery(OR=14.895,95%CI:9.741-22.776,P<0.001),constipation for 20-30 years(OR= 1.412,95%CI:0.925-2.156,P=0.010)were independent risk factors for difficult colonoscopy.Conclusions:This retrospective study identified several patient-related factors that influence the technical difficulty of colonoscopy.These findings had implications for practice and teaching of colonoscopy.
		                        		
		                        		
		                        		
		                        	
4.Construction and validation of a Nomogram model of intracranial infection after neurosurgery
Xiao-Ju MA ; Ying YU ; Yan LU ; Song-Qin LI ; Juan LIU ; Zheng WANG ; Feng ZANG ; Hui-Ping HUANG ; You-Peng CHEN ; Yong-Xiang ZHANG ; Wei-Hong ZHANG ; Zhan-Jie LI
Chinese Journal of Infection Control 2023;22(12):1483-1492
		                        		
		                        			
		                        			Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96%.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P>0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P<0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.
		                        		
		                        		
		                        		
		                        	
5.Herbal Textual Research on Dendrobii Caulis in Famous Classical Formulas
Ju-run ZHAO ; Jia-chen ZHAO ; Yi-han WANG ; Yan JIN ; Wei ZHANG ; Hua-sheng PENG ; Qiu-jie CAI ; Bing LI ; Hong-jun YANG ; Hua-min ZHANG ; Zhi-lai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):215-228
		                        		
		                        			
		                        			Through consulting the ancient herbal and medical books, combined with the field investigation, the name, origin, collection and processing of Dendrobium medicinal materials were researched, which provided a basis for the development of famous classical formulas containing this kind of herbs. Due to the wide distribution of D. officinale, the Dendrobium species represented by D. officinale and D. huoshanense, which are short, fleshy and rich in mucus, should be the most mainstream of Dendrobium medicinal materials in previous dynasties. Compared with Shihu, Muhu with loose texture, long and hollow is born on trees. According to the characteristic description, it should be D. nobile, D. fimbriatum and so on, of which D. nobile was the mainstream. The Chinese meaning of Jinchai was confused in the past dynasties, so it was not suitable to be treated as a plant name. The production areas of Dendrobium medicinal materials in the past dynasties have changed with the discovery of varieties, artificial cultivation and other factors. Lu'an, Anhui province, was the earliest recorded in the Han and Wei dynasties. Since the Tang and Song dynasties, it had been extended to Guangdong and Guangxi, and it was considered that "Dendrobii Caulis in Guangnan was the best". In the Ming dynasty, Sichuan and Zhejiang products were highly praised, and in the Qing dynasty, Huoshan products were highly praised. Dendrobium medicinal materials had been used as medicine by stems in all dynasties. The medicinal materials were divided into fresh products and dry products. The fresh products can be used immediately after removing the sediment from the roots. The dry products need further processing, most of them used wine as auxiliary materials for steaming, simmer to paste or decoction into medicine. D. officinale and D. huoshanense have special processing specifications since the middle of Qing dynasty, that is, "Fengdou". According to the research results, in Ganluyin, the effect of Dendrobium medicinal materials is mainly heat clearing, and D. nobile with bitter taste can be selected. The main effect of Dendrobium medicinal materials in Dihuang Yinzi is tonic, D. officinale or D. huoshanense can be selected. 
		                        		
		                        		
		                        		
		                        	
6. miR-338-3p Targets and Regulates RNF121 to Promote the Proliferation and Invasion of Human Lung Cancer A549 Cells
Jing-Chen XIE ; Chuan LI ; Zhan-Qing ZHAO ; Xie-Ju XIE
Chinese Journal of Biochemistry and Molecular Biology 2021;37(7):908-916
		                        		
		                        			
		                        			 Recent studies have shown that miR-338-3p plays an important role in the proliferation and invasion of lung cancer, but whether miR-338-3p regulates lung cancer proliferation and invasion through targeting ring finger protein 121 (RNF121) is still unclear. In order to explore its mechanism, the normal lung cell line MRC-5 and the non-small cell lung cancer line A549 were cultured in vitro. Using qRTPCR and Western blotting detection, we found that the expression of miR-338-3p in A549 lung cancer cells was lower than that in MRC-5 cells, while RNF121 expression increased (P<0. 05). The miR-338-3p bound to the 3′UTR of RNF121 was predicted by TargetScan (http:/ / www. targetscan. org/mamm_31/) target gene prediction software. The dual luciferase reporter confirmed the complementary combination. We constructed a shRNA vector targeting RNF121 and transfected cells, used CCK8 experiments to detect cell proliferation in each group, employed Annexin V-FITC/PI double staining to detect cell apoptosis, performed Transwell experiments and cell colony formation experiments to detect cell invasion and clonal proliferation ability of each group. Cells of each group were inoculated under the skin of nude mice and we drew the tumor growth curve and the size of the tumor were measured. Then the tumor tissue was obtained and TUNEL staining was used to detect apoptosis in the tissue. Compared with the blank group, the cell proliferation, invasion, and cell cloning ability in the miR-338-3p mimic and sh-RNF121 groups were inhibited, but apoptosis was significantly induced. At the same time, in vivo experiments found that the ability to form tumors was reduced, and apoptosis in tumor tissues was increased (P<0. 05). The miR-338-3p group had a higher cell proliferation activity, invasion and colony-forming ability but lower tumorigenicity and apoptosis in tumor tissues (P<0. 05). Compared with the blank group, no significant difference was found in the NC group and miR-338-3p inhibitor+sh-RNF121 group (P>0. 05). In summary, miR-338-3p can target the expression of RNF121 to inhibit the proliferation and invasion of A549 cells and inhibit the growth of subcutaneous transplanted tumors in nude mice. RNF121 is expected to become a new target for the treatment of non-small cell lung cancer. 
		                        		
		                        		
		                        		
		                        	
7.Effect of acupuncture and moxibustion on post-stroke constipation: a network Meta-analysis.
Ou-Feng TANG ; Si-Min HUANG ; Xin-Xin YE ; Qi-Xi LIU ; Ting-Ting CHEN ; Chen-Ju ZHAN
Chinese Acupuncture & Moxibustion 2020;40(9):1011-1016
		                        		
		                        			OBJECTIVE:
		                        			To systematically review the therapeutic effect of acupuncture-moxibustion therapies on post-stroke constipation based on the network Meta-analysis.
		                        		
		                        			METHODS:
		                        			The randomized controlled trials of acupuncture and moxibustion for post-stroke constipation were retrieved from the databases, starting from the time of establishment through to June, 2019, i.e. the PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, Wanfang and VIP. The literature was selected according to inclusion and exclusion criteria, the quality of literature was evaluated by bias risk assessment tool of Cochrane Review Manual 5.3 and the data was statistically analyzed by softwares of Stata 13.1 and R Language.
		                        		
		                        			RESULTS:
		                        			A total of 28 trails were included, involving 9 intervention methods. The therapeutic effect was arranged from high to the low according to the surface under cumulative ranking area (SUCRA), i.e. acupuncture combined with medication (0.86), warm needling (0.83), electroacupuncture combined with medication (0.68), electroacupuncture (0.68), moxibustion (0.50), auricular point sticking (0.44), acupuncture (0.31), Chinese herbal medicine (0.12) and western medication (0.04).
		                        		
		                        			CONCLUSION
		                        			Acupuncture- moxibustion therapies have superiority on treating post-stroke constipation, acupuncture combined with medication has the most optimum therapeutic effect and the therapeutic effect of acupuncture-moxibustion combined with medication is superior to the single treatment of medication.
		                        		
		                        		
		                        		
		                        	
8.Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.
Yang LI ; Pei-Yuan LI ; Shi-Jing SUN ; Yuan-Zhang YAO ; Zhan-Fei LI ; Tao LIU ; Fan YANG ; Lian-Yang ZHANG ; Xiang-Jun BAI ; Jing-Shan HUO ; Wu-Bing HE ; Jun OUYANG ; Lei PENG ; Ping HU ; Yan-An ZHU ; Ping JIN ; Qi-Feng SHAO ; Yan-Feng WANG ; Rui-Wu DAI ; Pei-Yang HU ; Hai-Ming CHEN ; Ge-Fei WANG ; Yong-Gao WANG ; Hong-Xu JIN ; Chang-Ju ZHU ; Qi-Yong ZHANG ; Biao SHAO ; Xi-Guang SANG ; Chang-Lin YIN
Chinese Journal of Traumatology 2019;22(1):1-11
		                        		
		                        			
		                        			Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
		                        		
		                        		
		                        		
		                        			Abdomen
		                        			;
		                        		
		                        			surgery
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Drainage
		                        			;
		                        		
		                        			methods
		                        			;
		                        		
		                        			Evidence-Based Medicine
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Practice Guidelines as Topic
		                        			;
		                        		
		                        			Societies, Medical
		                        			;
		                        		
		                        			organization & administration
		                        			;
		                        		
		                        			Surgical Wound Infection
		                        			;
		                        		
		                        			prevention & control
		                        			;
		                        		
		                        			Traumatology
		                        			;
		                        		
		                        			organization & administration
		                        			;
		                        		
		                        			Vacuum
		                        			
		                        		
		                        	
9.Progress in rolling circle amplification in biological detection.
Zhongxu ZHAN ; Ju LIU ; Bolu CHEN ; Yizhou TANG ; Guanhua CHEN ; Hengyi XU
Chinese Journal of Biotechnology 2019;35(7):1206-1213
		                        		
		                        			
		                        			Rolling circle amplification is a rapid, sensitive and isothermal single-stranded DNA amplification technique that can be used with staining or probes to amplify the detection signal. This technology has been widely used in biological detection and other aspects. The present paper introduces how to design rolling circle amplification, summarize its application in the detection of pathogens, nucleic acid tumor markers, proteins, biological small biomolecules, and viruses in recent years and prospects for future development.
		                        		
		                        		
		                        		
		                        			DNA, Single-Stranded
		                        			;
		                        		
		                        			Nucleic Acid Amplification Techniques
		                        			
		                        		
		                        	
10.Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis.
Zhan-Guo LI ; Yi LIU ; Hu-Ji XU ; Zhi-Wei CHEN ; Chun-De BAO ; Jie-Ruo GU ; Dong-Bao ZHAO ; Yuan AN ; Lie-Ju HWANG ; Lisy WANG ; Joel KREMER ; Qi-Zhe WU
Chinese Medical Journal 2018;131(22):2683-2692
		                        		
		                        			Background:
		                        			Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.
		                        		
		                        			Methods:
		                        			ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.
		                        		
		                        			Results:
		                        			ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.
		                        		
		                        			Conclusions:
		                        			Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.
		                        		
		                        			Clinical Trial Identifier
		                        			NCT00856544 and NCT00413699.
		                        		
		                        		
		                        		
		                        			Administration, Oral
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Arthritis, Rheumatoid
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Piperidines
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Protein Kinase Inhibitors
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Pyrimidines
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Pyrroles
		                        			;
		                        		
		                        			adverse effects
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Surveys and Questionnaires
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
            
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