1.Effects of 5'-N-ethylocarbo-xamidoad-enosine on brain ischemia-reperfusion oxidative injury and levels of miR-29b and miR-125b in rats
Ze LI ; Jun TAN ; Qiu-Li MING ; Yan-Wei LI
The Chinese Journal of Clinical Pharmacology 2024;40(10):1448-1452
		                        		
		                        			
		                        			Objective To investigate the effects of 5'-N-ethylocarbo-xamidoad-enosine(NECA)on cerebral ischemia-reperfusion oxidative injury and the levels of miR-29b and miR-125b in rats.Methods SD rats were divided into sham-operation,model,experimental and positive control groups with 12 rats in each group.Cerebral ischemia-reperfusion model was established in all the other 3 groups except control group.7 days before modeling,sham-operation group and model group were intraperitoneally injected with the same amount of normal saline,and experimental group was injected with 1.5 mg·kg-1 NECA,and positive control group was injected with 2.0 mg·kg-1 nimodipine.The rats in 4 groups were given the drug once a day for 7 days.Cerebral ischemia-reperfusion model was established by middle cerebral artery embolization in all the other 3 groups except sham-operation group.After the modeling was successful,the serum oxidative stress indexes glutathione(GSH),superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA)of rats were determined by enzyme-linked immunosorbent assay,and the levels of miR-29b and miR-125b in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The SOD levels of sham-operation,model,experimental and positive control groups were(57.82±6.87),(10.75±0.24),(32.24±3.42)and(29.45±4.11)U·mL-1;the levels of GSH were(20.62±3.12),(9.45±1.92),(16.78±1.85)and(15.39±2.02)U·mg-1;the levels of CAT were(3.25±0.42),(0.85±0.11),(2.18±0.34)and(1.98±0.32)U·L-1;the levels of MDA were(0.42±0.09),(1.35±0.42),(0.75±0.06)and(0.72±0.08)nmol·mg-1;the expression levels of miR-29b in brain tissue were 1.02±0.11,0.42±0.02,0.84±0.08 and 0.87±0.10;the expression levels of miR-125b in brain tissue were 1.00±0.11,0.48±0.05,0.75±0.08 and 0.74±0.07,respectively.There were statistically significant differences between sham-operation group and model group(all P<0.05).Compared with experimental group and positive control group,there were statistically significant differences in the above indexes(all P<0.05).Conclusion NECA can improve oxidative damage and increase the expression levels of miR-29b and miR-125b in cerebral ischemia-reperfusion rats.
		                        		
		                        		
		                        		
		                        	
2.Etiology composition and prognosis of pediatric chronic critical illness in a pediatric intensive care unit.
Zi-Feng TAN ; En-Si LI ; Wei-Bin ZHONG ; Dong-Ru YANG ; Ke-Ze MA ; Zhi-Jun LAI ; Su-Jun CHEN ; Man ZHENG
Chinese Journal of Contemporary Pediatrics 2023;25(8):843-848
		                        		
		                        			OBJECTIVES:
		                        			To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU).
		                        		
		                        			METHODS:
		                        			The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed.
		                        		
		                        			RESULTS:
		                        			Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05).
		                        		
		                        			CONCLUSIONS
		                        			The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Critical Illness
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Child, Hospitalized
		                        			;
		                        		
		                        			Chronic Disease
		                        			;
		                        		
		                        			Intensive Care Units, Pediatric
		                        			
		                        		
		                        	
3.Comparison of vesselplasty and percutanous kyphoplasty in the treatment of Kümmell disease.
Shu-Qiang YAO ; Rui WU ; Ji-Ping ZHOU ; Yong-Jun YANG ; Yuan-Chao TAN ; Kai YANG ; Jia-Jia LI ; Ze-Wei JIANG ; Bin LIU
China Journal of Orthopaedics and Traumatology 2022;35(5):429-434
		                        		
		                        			OBJECTIVE:
		                        			To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease.
		                        		
		                        			METHODS:
		                        			The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T10 fracture, 3 cases of T12 fracture, 9 cases of L1 fractures, 5 cases of L2 fractures and 2 cases of L3 fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T10 fracture, 1 case of T11 fracture, 6 cases of T12 fracture, 10 cases of L1 fracture and 1 case of L3 fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation.
		                        		
		                        			RESULTS:
		                        			All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison(P<0.05), and there was no statistically difference between the two groups(P>0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant(P<0.05).
		                        		
		                        			CONCLUSION
		                        			Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.
		                        		
		                        		
		                        		
		                        			Bone Cements
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fractures, Compression/surgery*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Kyphoplasty/methods*
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Osteoporotic Fractures/surgery*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Spinal Fractures/surgery*
		                        			;
		                        		
		                        			Spondylosis
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Vertebroplasty
		                        			
		                        		
		                        	
4.Common susceptibility loci in both systemic sclerosis and localized scleroderma identified using genetic analysis.
Yun LI ; Wen-Jun WANG ; Wei-Wei CHEN ; Xue FAN ; Lu CAO ; Ze-Yu XING ; Qi ZHEN ; Qiong-Qiong XU ; Chen-Yu ZHU ; Hui-Yao GE ; Dian CHEN ; Rui-Xue ZHANG ; Chang SHU ; Wei DU ; Shi-Rui CHEN ; Xie YUAN ; Hui ZHANG ; Xia HU ; Xu-Ming MAO ; Qiu-Ning SUN
Chinese Medical Journal 2020;133(19):2370-2372
		                        		
		                        		
		                        		
		                        	
5.Exploration on Biological Basis Underling Different Syndromes of Nontraumatic Osteonecrosis of Femoral Head Based on Network Pharmacology
Tai-xian LI ; Yan-qiong ZHANG ; Ze-qing HUANG ; Meng-ge SONG ; Biao TAN ; Rong-tian WANG ; Na LIN ; Wei-heng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(16):192-204
		                        		
		                        			
		                        			Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.
		                        		
		                        		
		                        		
		                        	
6.HBsAg Levels Normalized to the Same Hepatic Parenchyma Cell Volume Is Correlated with Pathological Progression but Not HBeAg Status
Lei TAN ; Tao WU ; Yan LV ; Wei-li WANG ; Jie REN ; Rong-qin ZHENG ; Ze-qian WU
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(5):747-753
		                        		
		                        			
		                        			【Objective】To study retrospectively the serum hepatitis B surface antigen(HBsAg)and HBsAg normal⁃
ized to the same hepatic parenchyma cell volume(HPCV),namely,the same hepatic cell quantities,between HBeAg-
positive and HBeAg-negative chronic hepatitis B(CHB).【Methods】A total of 168 CHB patients who had undergone liv⁃
er biopsy and test of serum HBsAg levels due to their disease in the Third Affiliated Hospital of SunYat-sen University
were selected as the study subjects. The serum HBsAg levels,as well as HBsAg levels normalized to HPCV(hepatic cell
quantities)were compared between HBeAg-positive and HBeAg-negative CHB,respectively.【Results】There was statis⁃
tically significant difference in serum HBsAg levels between HBeAg-positive and HBeAg-negative CHB(P = 0.028),
while there was no statistical difference in HBsAg normalized to HPCV(P = 0.073). There were no correlations between
serum HBsAg and liver inflammation grades(HBeAg-positive:r s = 0.020,P = 0.876 & HBeAg-negative:r s = 0.037,P =0.711). Similarly,there were no correlations between HBsAg and hepatic fibrosis stages(HBeAg-positive:r s = 0.087,
P = 0.488 & HBeAg-negative:r s = 0.144,P = 0.148). Nevertheless,statistically significant positive correlations were
shown between HBsAg normalized to HPCV and liver inflammation grades(HBeAg-positive:r s = 0.309,P = 0.012 &
HBeAg-negative:r s = 0.389,P < 0.001). Similarly,the HBsAg normalized to HPCV and hepatic fibrosis stages were
shown to be statistically significantly correlated(HBeAg-positive:r s = 0.490,P < 0.001 & HBeAg-negative:r s = 0.599,
P < 0.001).【Conclusions】Serum HBsAg normalized to HPCV but not HBsAg levels,is correlated with liver inflamma⁃
tion grades as well as hepatic fibrosis stages positively in both HBeAg-positive and HBeAg-negative CHB. But there is
no difference in serum HBsAg levels normalized to HPCV between HBeAg-positive and HBeAg-negative CHB.
		                        		
		                        		
		                        		
		                        	
7.Stress, Stressors And Coping Strategies Among University Nursing Students
Retneswari Masilamani ; Myat Moe Thwe Aung ; Hamidah Othman ; Aini Abu Bakar ; Tan Chung Keat ; Sugapriyan Ravichandran ; Lim Kit Wing ; Chuah Wei Hong ; Lim Kok Hong ; Ng Elson ; Tan Jef Wayna ; Vickneshan Selvathurai ; Tan Ze Xuan ; Surein Prasad Jagajarantan
Malaysian Journal of Public Health Medicine 2019;19(2):20-28
		                        		
		                        			
		                        			Literature has documented that student nurses undergo stress in their academic and clinical setting. This raises concerns because stress during undergraduate training may result in psychological or emotional impairment during the nurses’ professional life and ultimately affect the quality of patient care. The Objective of the study was to study the prevalence of stress, and the association between sociodemographic factors, stressors and coping strategies with stress. This was a cross-sectional study on 96-year 1-3 nursing students from a government university done between 2015-2018. Bahasa Malaysia translated The General Health Questionnaire, Stressors in Nursing Student Scale Questionnaire and Brief COPE Questionnaire was used in this study. This study had Malay (95.9%) and female (91.7%) dominated population. The prevalence of stress in student nurses was 25%. No association was reported between sociodemographic factors and stress. Among the 4 stressors educational, clinical, confidence and financial, clinical stressor scored the highest mean 6.40 (SD±3.66). Confidence stressor (AOR=1.26 95% CI 1.04-1.53) was the only stressor associated with stress. The top 3 coping strategies practiced by the student nurses were religion (praying), acceptance and planning. Self-blame (AOR 8.18 95% CI 1.86-35.91) was the only coping strategy associated with stress. Stress management programmes, and workshops on stress and coping strategies should be conducted yearly to ensure a well-balanced environment for good learning experiences and prevent stress related health problems and improved academic performance.
		                        		
		                        		
		                        		
		                        	
8.Tung Tree (Vernicia fordii) Genome ProvidesA Resource for Understanding Genome Evolution and Improved Oil Production
Zhang LIN ; Liu MEILAN ; Long HONGXU ; Dong WEI ; Pasha ASHER ; Esteban EDDI ; Li WENYING ; Yang XIAOMING ; Li ZE ; Song AIXIA ; Ran DUO ; Zhao GUANG ; Zeng YANLING ; Chen HAO ; Zou MING ; Li JINGJING ; Liang FAN ; Xie MEILI ; Hu JIANG ; Wang DEPENG ; Cao HEPING ; Provart J. NICHOLAS ; Zhang LIANGSHENG ; Tan XIAOFENG
Genomics, Proteomics & Bioinformatics 2019;17(6):558-575
		                        		
		                        			
		                        			Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73% repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.
		                        		
		                        		
		                        		
		                        	
9.Trans-differentiation from osteoblasts to adipocytes in indirect co-culture
wen Xin QI ; ze Rong AN ; fei Yi LI ; hong Xiao YUAN ; ping Jun CHEN ; yuan Wei TAN ; bin Yan YE
Chinese Journal of Tissue Engineering Research 2017;21(28):4429-4435
		                        		
		                        			
		                        			BACKGROUND:Co-culture technique makes different kinds of ceils cultured in the same system.The trans-differentiation from osteoblasts to adipocytes is usually analyzed under the action of adipogenesis inducers in vitro,but the cellular interactions in vivo are neglected.OBJECTIVE:To investigate the trans-differentiation from osteoblasts to adipocytes in indirect co-culture using Transwell system.METHODS:Mouse preadipocytes 3t3-l1 were induced to adipocytes.There were three groups:group A:mature adipocytes in the lower chamber of Transwell system;group B:mouse osteoblasts MC3T3-E1 in the upper chamber of Transwell system according to a ratio of 1:4 (MC3T3-E1:3t3-l1);group C:mouse osteoblasts MC3T3-E1 alone.At 7,14,and 21 days the cell morphology was observed under inverted phase contrast microscope,the relative level of triglyceride,expression of peroxisome proliferator-activated recoptor y2 in each group were detected,and red oil O staining and alizarin red staining were performed.The cell proliferation inhibition rate in the groups B and C were detected at 0,24 and 36 hours.RESULTS AND CONCLUSION:At 2 weeks after culture,spindle-shaped 3t3-l1 coils changed into round,the light and round lipid droplets in the cytoplasm were increased and were reserved after identified by oil red O staining.In the group B,the cells presented with spindle shape with no transparent lipid droplets after 7-day co-culture until black granules and small round lipid droplets appeared on day 14;and the cells changed from spindle shape to oval or round,and larger lipid droplets were found on day 21.Alizarin red staining results:the staining region in the group B was on a decline with time,while the group C showed no significant changes at each time point and all appeared with large staining region.Oil red O staining results:the staining region in the group B increased gradually in a time-dependant manner,while the group C was negative for oil red O staining and showed no significant changes at different time points.The relative level of triacylglycerol in the group B was increased with time,and there was significant difference between groups A and B (P <0.05),and the group C showed no significant differences (P > 0.05).The coll proliferation inhibiting rate in the group B was increased with time,which showed significant difference from the group C (P < 0.05).The expression level of peroxisome proliferator-activated recoptor y2 in the group B was on a rise with time,which had significant difference compared with the groups A and C (P < 0.05).These results indicate that the trans-differentiation from osteoblasts to adipocytes appears in the Transwell system,and metabolic products and cytokines of adipocytes obviously inhibit the proliferation of osteoblasts,but all above conclusions need to be studied in depth.
		                        		
		                        		
		                        		
		                        	
10.Single -dose and multi -dose bioavailability of isosorbide -5 -mononitrate sustbilityained release capsules in Chinese healthy subjects
Ze-Li CHUN ; Wen-Fang LIU ; Yang LIN ; Ke-Xu YANG ; Gui-Ping ZHAO ; Chun-Yan LU ; Li TAN ; Ying-Chao ZHANG ; Wei WU ; Wei SUO ; Jing LI ; Zi-Jie ZHOU ; Hai-Yan DU ; Qi QIU ; Ying ZHAO ; You-Ping LIU
The Chinese Journal of Clinical Pharmacology 2015;(17):1727-1731
		                        		
		                        			
		                        			Objective To compare the pharmacokinetic profiles between a new generic and a branded reference formulation of isosorbide -5 -mononitrate sustained release capsules , and to assess the bioequivalence of the two products in healthy Chinese male subjects.Methods Fifty subjects participated in the open -label, randomized -sequence, 2-way crossover study.Twenty-four subjects and 26 subjects were ran-domly assigned in a 1:1 ratio to receive single dose (50 mg) or multiple dose (50 mg, qd, 6 days) of the test or reference formulation , followed by a one -week washout period and administration of the alternate formulation , respectively.Serial blood samples were collected , and isosorbide -5 -mononitrate concentration in plasma was determined by LC-MS/MS.The relative bioavailability and related parameters of pharmacokinetics were calculated. Results The pharmacokinetic parameters of test formulation and the reference formulation after a single dose were as follows: Cmax were ( 554.18 ± 117.84 ) and (526.29 ±91.58 )μg· L-1; AUC0-t were ( 7834.21 ±1227.70 ) and (7658.86 ±927.74) h· μg· L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 99.82%-113.03%and 99.13%-106.43%of reference formulation , respectively.The pharmacokinetic parame-ters of test formulation and the reference formulation after multiple doses were as follows :Cmax were (612.96 ±171.32) and (527.12 ±114.36 ) μg · L-1; AUC0-t were ( 8408.71 ±1321.91 ) and ( 7781.88 ±1325.12 ) h · μg · L-1 , respectively.The 90% confidential interval of Cmax and AUC0-t of test formulation were 108.44% -122.17% and 105.35%-111.57% of reference formulation , respectively.The 90% confidence interval of Cmax and AUC0-t of isosorbide-5-mononitrate for the test formulation after single and multiple oral doses were fall within 70%-143%and 80%-125%of reference formulation.Conclusion The test formulation was considered bioequivalent to the reference formulation.
		                        		
		                        		
		                        		
		                        	
            

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