Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases， malignant tumors， central nervous system diseases， and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development， the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe， America， and China， the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects， including lack of relevant laws and regulations， a higher risk of radiopharmaceuticals， dilemmas in ethical review， and insufficient radiation protection. Response principles and measures were proposed from four aspects， including improving regulations and policies， enhancing radiological protection for all parties involved in the research， strengthening ethical review， and reinforcing the training of relevant personnel， to enhance the quality and level of clinical research on radiopharmaceuticals.

Objective:To evaluate the efficacy and safety of ultrasound-guided high intensity focused ultrasound(HIFU)on pain intensity,pain sensation and overall survival in patients with advanced pancreatic cancer. Methods:Clinical data of advanced pancreatic cancer patients treated by HIFU were collected from the patients enrolled during August 2020 to September 2022 at the second department for oncology of Yueyang Hospital of Integrated Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine.In this study,SPSS 26.0 software was used for the statistical analysis of NRS score and BPI score.The Kaplan-Meier survival analysis method was applied to calculate the median overall survival(OS)and then the survival curve was drawn.At the same time,the incidence of related adverse reactions during and after HIFU treatment was counted. Results:(1)Among the 45 patients,30 patients received HIFU combined with chemotherapy,and the other 15 patients only received HIFU.(2)Among the 45 patients,32 patients had pain relief after HIFU treatment,and the NRS score kept decreased across 1 week,2 weeks,3 weeks and 1 month after HIFU treatment(P＜0.05).The pain sensation score of BPI scale also decreased correspondingly,and the difference was statistically significant(P＜0.05).(3)The median OS of 45 patients was 11.1 months(95％Cl:9.30-1 2.90),of which 30 patients treated with HIFU combined chemotherapy had a median OS of 12.4 months(95％Cl:9.1 8-15.62),and 15 patients treated with HIFU only had a median OS of 4.6 months(95％Cl:1.11-8.10).(4)No serious adverse events were observed in all patients during and after HIFU treatment.Only 5 patients had asymptomatic mild elevation of blood amylase,and the incidence of mild adverse reactions was 11.1％. Conclusion:HIFU can effectively relieve pain and prolong the median survival time in patients with advanced pancreatic cancer.

Objective:To analyze fetal sex chromosome abnormalities in prenatal diagnosis based on amniotic fluid cell culture.Methods:Clinical data of 12 164 pregnant women who underwent amniocentesis in Maternal and Child Health Hospital of Hunan Province from January 2017 to December 2020 were retrospectively analyzed. For those diagnosed with fetal sex chromosome abnormalities, the results of karyotyping and chromosome microarray analysis (CMA) were analyzed and described.Results:(1) Among the 12 164 cases, fetal sex chromosome abnormalities were detected in 387 cases (3.2%), including 351 cases with abnormal sex chromosome karyotype and 36 with sex chromosome microdeletion/microduplication. (2) High-risk patients indicated by non-invasive prenatal test (NIPT) had the highest proportion of sex chromosomes abnormalities (74.2%, 287/387), followed by those with other ultrasound abnormalities (8.5%, 33/387), high risk of Down syndrome screening (7.0%, 27/387), advanced maternal age (4.7%, 18/387), history of adverse pregnant or delivery (3.3%, 13/387), and nuchal translucency thickening or cervical lymphatic hygroma (2.3%, 9/387). (3) Detected chromosome karyotype abnormalities included numerical abnormalities [73.2%(257/351)], mosaicism [18.8(66/351)], and structural abnormalities [8.0%(28/351)], among which, 47,XXY [46.7%(120/257)], 45,X/46,XX[48.5%(32/66)], and X chromosome deletion [39.3%(11/28)] were the most common, respectively. Among 36 sex chromosome microdeletions/microduplications cases, 15(41.7%) were with pathogenic copy number variation (CNV), including 14 cases of X chromosome microdeletion/microduplication; 7(19.4%) with benign CNV, and 14(38.9%) with CNV of unknown clinical significance. The fragment size [ M (min-max)] of the 15 pathogenic CNV was 1.68 Mb(0.37-9.20 Mb). Of the nine cases with microdeletions, seven were found with deletion in the Xp22.31 region. Conclusions:Numerical abnormalities are the most common fetal sex chromosome abnormalities detected from amniotic fluid samples. Others included mosaicism and chromosome structure abnormalities.

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

OBJECTIVE: To explore the genetic etiology of a pedigree with mental retardation and hypotonia by using chromosome microarray analysis (CMA), low coverage massive parallel copy number variation sequencing (CNV-seq) and quantitative PCR (qPCR). METHODS: Genomic DNA was extracted from peripheral blood samples from two male patients and healthy members from the pedigree. CNV-seq was carried out for one patient. Suspected CNV was verified by qPCR. CNV-seq or single nucleotide polymorphism array (SNP array) were carried out for another patient and his family members. RESULTS: Both patients showed severe hypotonia and global development delay, in particular language delay. CNV-seq and SNP array indicated that both patients had carried a Xq28 duplication, with spanned 0.26 Mb and 0.42 Mb, respectively. Both duplications encompassed the MECP2 gene. CNV-seq analysis of their family members confirmed that the mother and one sister had carried similar duplications, while an elder brother was normal. CONCLUSION CNV-seq and CMA are rapid and effective tools for the diagnosis of MECP2 duplication syndrome in children with mental retardation, hypotonia and recurrent infections.

OBJECTIVE: To carry out prenatal diagnosis for a fetus with high risk predicted by non-invasive prenatal testing (NIPT). METHODS: Next-generation sequencing (NGS) was used to analyze free fetal DNA (ffDNA) in the maternal plasma. Chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were used to ascertain copy number variation in the fetus and its parents. RESULTS: SNP-array analysis and chromosomal karyotyping revealed that the fetus had a 15.018 Mb duplication at 4q34.1q35.2 and a 7.678 Mb duplication at 21q11.2q21.1, which were derived from a t(4;21)(q34.1;q21.1) translocation carried by its mother. CONCLUSION NIPT is capable of detecting submicroscopic chromosomal abnormalities of the fetus. Combined use of genetic techniques, in particular SNP-array, is crucial for the diagnosis of partial trisomy 21q in this case.

OBJECTIVE: To explore the genetic basis for a patient with premature ovarian insufficiency. METHODS: Chromosomal G-banding and C-banding, single nucleotide polymorphism array (SNP-array), fluorescence in situ hybridization (FISH) and Y chromosome microdeletion assay were used for the analysis. RESULTS: With the combined techniques, the patient was found to carry a Xq;Yq translocation, with a karyotype of 46,X,der(X)t(X;Y)(q25;q12).ish der(X)(Tel XYp+,Tel XYq+,Yq12+). CONCLUSION Unbalanced Xq;Yq translocation probably underlay the premature ovarian insufficiency in this patient.

Objective To evaluate the effect of donor risk index (DRI) on the early prognosis of liver transplantation for acute-on-chronic liver failure (ACLF). Methods Clinical data of 159 ACLF recipients undergoing liver transplantation were retrospectively analyzed. According to the calculation formula of DRI, all recipients were divided into DRI < 1.65 group (n=96) and DRI≥1.65 group (n=63). Based on the Chronic Liver Failure Consortium acute-on-chronic liver failure score (CLIF-C ACLFs), all recipients were divided into CLIF-C ACLFs < 48 group (n=78) and CLIF-C ACLFs≥48 group (n=81). The early prognosis indexes including the length of intensive care unit (ICU) stay and the length of postoperative hospital stay of the recipients in each group were observed after liver transplantation. The 90 dsurvival rate of the recipients after liver transplantation was analyzed by Kaplan-Meier survival curve. The risk factors affecting the early prognosis of ACLF recipients after liver transplantation were analyzed by Cox's hazards regression model. Results The length of ICU stay and the length of postoperative hospital stay did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (both P > 0.05). The length of postoperative hospital stay did not significantly differ between the CLIF-C ACLFs < 48 group and CLIF-C ACLFs≥48 group (P > 0.05). The length of ICU stay in the CLIF-C ACLFs < 48 group was 4 (3-14) d, significantly shorter than 7 (1-33) d in the CLIF-C ACLFs≥48 group (P < 0.05). The CLIF-C ACLFs was a risk factor of the early prognosis of ACLF recipients after liver transplantation (P < 0.05). The postoperative 90 d survival rate did not significantly differ between the DRI < 1.65 group and DRI≥1.65 group (P > 0.05). The postoperative 90 d survival rate in the CLIF-C ACLFs < 48 group was 94%, significantly higher than 79% in the CLIF-C ACLFs≥48 group (P < 0.05). Conclusions The early prognosis of ACLF recipients after liver transplantation is correlated with the severity of the disease rather than the DRI. Liver transplantation should be performed early and promptly.

OBJECTIVE: To explore the prenatal screening and diagnosis for a pair of monochorionic-diamniotic (MCDA) twins discordant for 45,X/46,XX mosaicism. METHODS: Amniotic fluid samples were taken from both twins for whom non-invasive prenatal testing has signaled a high risk for sex chromosomal abnormality. Uncultured amniotic fluid was analyzed by fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array). Conventional G-banded karyotyping analysis was performed on the cultured amniotic fluid. RESULTS: Metaphase chromosome analysis showed that one of the twins had a mos 45,X[11]/46,XX[26] karyotype, while the other had a normal karyotype. FISH and SNP-array applied on uncultured amniotic fluid revealed about 30% mosaicism in one of the twins. The twins were confirmed to be monozygotic by SNP-array analysis. CONCLUSION To avoid confusion arising from discordant karyotypes in MCDA twins with abnormal non-invasive prenatal testing (NIPT) results, dual amniocentesis should be carried out to obtain amniotic fluid samples for chromosomal as well as molecular analysis. To determine the ratio of 45,X and 46,XX cells in Turner syndrome can provide valuable information for prenatal genetic counseling.
Amniocentesis ; Chromosomes, Human, X ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Mosaicism ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy. METHODS: Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed. RESULTS: The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo. CONCLUSION A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.
Child ; Developmental Disabilities ; genetics ; Epilepsy ; genetics ; Genetic Association Studies ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Protein-Serine-Threonine Kinases ; genetics ; Protein-Tyrosine Kinases ; genetics ; Sequence Deletion