Pharmacy education in Singapore adopts a patient-orientated approach. This article provides a general introduction to the education and practice of Pharmacy in Singapore through 3 major aspects,①Professional pharmacy degree;②Curriculum of the undergraduate and postgraduate pharmacy education;③Professional pharmacy practice and employment in Singapore.

Objective According investigate the expression of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury (HIRI),to determin the role of NLRP3 in the process of HIRI.Methods Established mice model of partial HIRI.Forty-two male C57BL/6 mice (aged 7 to 8 weeks,weight 20 to 25 g) were respectively divided into 7 groups:no-treatment control group,sham operation group,HIRI groups (2、6、12、24 h) and CY-09 group,6 mice in each group.The injury of the hepatic tissues in the 7 groups was analyzed based on detecting the levels of alanine transaminase (ALT),aspartate transaminase (AST),interleukin-1β (IL-1β),interleukin-18 (IL-18),tumor necrosis factor-α (TNF-α) by ELISA.HE and TUNEL staining were used to observe the pathological changes of liver tissues after HIRI.Western blotting assay were carried out to detect the expressions of NLRP3 and Caspase-1.Measurement data were expressed as mean ± standard deviation (Mean ± SD),and one-way variance analysis was used for comparison between groups.If the variance was not uniform,Dunnett C test was used.Results Serum ALT,AST,IL-1 β,IL-18 and TNF-α of mice detected in HIRI groups were higher than no-treatment control group and sham operation group at all endpoints (P ＜ 0.05).The relative expression of NLRP3 and Caspase-1 in the liver tissues of mice in the HIRI groups were significantly higher than that in the no-treatment control group and sham operation group.Serum ALT,AST,IL-1β,IL-18 and TNF-α of mice detected in CY-09 group were lower than HIRI groups at all endpoints (P ＜ 0.05).Less hepatocellular necrosis were exhibited in CY-09 group,comparing to HIRI groups.The hepatocyte apoptosis rate of mice in the CY-09 group was significantly lower than that in the 12 h HIRI group (P ＜ 0.05).The relative expression of NLRP3 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups.The relative expression of Caspase-1 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups except the no-treatment control group and sham operation group.Conclusions HIRI cause an increase in NLRP3 expression.The inhibition of NLRP3 can reduce HIRI.

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Objective To explore the genetic mutation spectrum of patients with hypertrophic cardiomyopathy (HCM) and analysis the correlation of genotype phenotype.Methods Collect peripheral venous blood of the 51 cases unrelated HCM patients(35 male and 16 female) in the Beijing Anzhen Hospital of Capital Medical University from 2013 to 2016.Sequence whole exons of human and analysis seven major mutations of HCM including:MYBPC3、MYH7 、TNNT2、TNNI3 、MYL2 、TPM1 and ACTC1.Then compare the results with clinical characteristics.Results 24 patients(47.1％) had 22 kinds of pathogenicity or possibly pathogenicity mutations.The 90.9％ (20/22) of mutations only occurred one time,except MYH7 gene's 663 amino acid and the TNND gene's 157 amino acid which had twice.The mutations of MYBPC3,MYH7,TNNT2,TNNI3,MYL2,TPM1 and ACTC1 accounted for 45.8％ (11/24),20.8％ (5/24),12.5％ (3/24),8.3％ (2/24),8.3％ (2/24),4.2％ (1/24),and 0 respectively.No amphimutation had been found that causes illness or possibly.Through the comparison of clinical features between Genotype positive(24 cases) and negative(27 cases) patients:the incidence of syncope(19.6％ vs.7.8％,P ＜ 0.05),the largest left ventricular wall thickness[(22.8 ± 2.6) mm vs.(20.0 ± 3.4) mm,P ＜ 0.05],family history of HCM(20.8％ vs.0,P ＜0.05),percentage of apical hypertrophy(25.5％ vs.11.8％,P ＜ 0.05);The ratio of left ventricular outflow tract obstruction in MYH7 group was higher than MYBPC3 group (80.0％ vs.18.2％,P ＜ 0.05).Conclusion MYBPC3 is the most common mutation gene in HCM patients.Phenotype is more severe in geuotype positive patients than in genotype negative patients.Relationship between specific gene mutations and clinical phenotype requires further study.

Objective:To investigate the fetal echocardiographic features and clinical phenotype of 22q11.2 microdeletion syndrome (22q11.2DS) and provide information for the diagnosis of fetal 22q11.2DS.Methods:We retrospectively retrieved information of 822 fetuses, who were diagnosed with congenital heart disease by fetal echocardiography, with results of low-coverage whole genome sequencing from the Genetic Database of Beijing Key Laboratory of Fetal Heart Disease and Maternal Fetal Medicine Research from January 2013 to April 2019. Phenotype, fetal echocardiographic features and genetic origin results of 46 fetuses with 22q11.2DS (22q11.2DS group) were summarized. Another 68 fetuses who were negative for 22q11.2DS but had conotruncal defects(CTD) were selected as control. Differences in fetal cardiac axis were compared between the two groups. Independent samples t test and Chi-square test were used for statistical analysis. Results:22q11.2DS was detected in 46 fetuses giving a total detection rate of 5.60% (46/822). The detection rates of 22q11.2DS in fetuses with CTD and non-CTD were 14.8% (45/305) and 0.2% (1/517), respectively ( χ2=74.253, P<0.001). Fetal cardiac axis was left-deviated in those with 22q11.2DS compared with those of the control [(61.7±15.3)°vs (55.7±13.4)°, t=-3.843, P=0.001]. Conclusions:CTD are the common clinical phenotypes of fetal 22q11.2DS. Fetal 22q11.2DS should be considered and the corresponding prenatal genetic diagnosis is highly suggested when the fetus is diagnosed with CTD especially combined with an enlarged cardiac angle.

Objective:To summarize the echocardiography and pathological features of fetal Kabuki syndrome.Methods:This study retrospectively analyzed the echocardiography and pathological features of seven fetuses with KMT2D pathogenic variants confirmed by copy number variation sequencing, and who were identified as complex congenital heart disease by fetal echocardiography, at Beijing Anzhen Hospital, Capital Medical University and other multi-center collaborative hospitals on fetal congenital heart diseases from January 2013 to May 2018. All the seven fetuses were artificially aborted. Descriptive statistics were used for data analysis. Results:(1) The seven pregnant women aged 29 (27-32) years and had an abortion at 23 (22-25) gestational weeks. There were three male and four female fetuses. (2) Pathogenic mutations in KMT2D gene were detected in all seven cases, including one nonsense mutation and six frameshift mutations. (3) All fetuses had left heart obstruction with or without aortic arch dysplasia/interruption of the aortic arch. There were three with hypoplastic left heart syndrome, two with a single ventricle, one with aortic atresia, and one with severe mitral valve dysplasia. Other cardiovascular abnormalities included aortic arch branch abnormalities, double-outlet of the right ventricle, ventricular septal defect, tricuspid atresia, pulmonary valve stenosis (nearly atresia) complicated by pulmonary dysplasia, persistent left superior vena cava, and patent or closed foramen ovale. Secondary changes included enlargement of the right atrium and right ventricle, and dilatation of the pulmonary artery or ductus arteriosus. (4) Four of the seven fetuses showed multiple extracardiac system abnormalities, including facial deformities (two cases), pulmonary dysplasia (two cases), digestive abnormalities(two cases), and urogenital system abnormalities (two cases). Conclusions:The main features of echocardiography for fetal Kabuki syndrome are left heart obstruction, often complicated by other congenital cardiovascular abnormalities.

Objective:To investigate the genetic etiology of fetal conotruncal heart defects (CTDs) and to evaluate the performance of copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) in identifying the genetic etiology.Methods:This retrospective study involved 196 fetuses diagnosed with CTDs by fetal echocardiography in Beijing Anzhen Hospital, Capital Medical University from June 2017 to December 2021. CNV-seq was performed to screen for chromosomal abnormalities [aneuploidy and copy number variations (CNVs)] in the fetuses and their parents, and then WES was performed if CNV-seq was negative. The diagnostic yields of genetic abnormalities [aneuploidy+CNVs+single nucleotide variations (SNVs)] for different types of CTDs were compared using Chi-square test. Results:CNV-seq revealed 54 cases (27.6%, 54/196) with chromosomal abnormalities, including 14 (7.1%, 14/196) aneuploidies, 39 (19.9%, 39/196) CNVs and one aneuploidy complicated by CNVs. Together with another 13 fetuses with pathogenic or likely pathogenic SNVs detected by WES among the rest 142 cases whose CNV-seq results were negative, the total detection rate of genetic abnormalities was 34.2% (67/196). WES increased the diagnostic yield for CTDs by 9.2% (13/142). There was significant difference in the diagnostic yields for different types of CTDs ( χ2=20.31, P=0.002). The diagnostic yield was relatively high for interrupted aortic arch of type B, absent of the pulmonary valve -type of tetralogy of Fallot (9/10 and 8/12), but low for transposition of the great arteries (12.5%, 5/40). Conclusions:CNVs are the common genetic abnormalities in fetal CTDs, and SNVs are also detected in some cases. It is recommended that all fetuses with CTDs should undergo genetic testing. CNV-seq should be used in combination with WES if possible to improve the identification of genetic etiology and provide reference for genetic counseling.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

Based on the"You Gu Wu Yun"theory in traditional Chinese medicine(TCM),this paper believes that"Gu"in"You Gu Wu Yun"is extended to"state"from the perspective of"TCM state".In order to avoid the adverse reactions of TCM,the macro,meso,and micro three views should be used together,and macro,meso,and micro parameters should be integrated.We should also carefully identify the physiological characteristics,pathological characteristics,constitution,syndrome,and disease of human body by combining qualitative and quantitative method,highlighting the relationship between the prescription and the"state".The correspondence between prescription and the"state"will reduce the risk of adverse reactions of TCM.In this paper,we hope to focus on the guiding role of the"You Gu Wu Yun"theory in TCM research,to give full play to the characteristics and advantages of TCM,and to dialectically treat the role of TCM.

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .