Objective:To block family transmission of a small fragment copy number variation (CNV) with combined 1 Mb resolution preimplantation genetic testing for aneuploidy (PGT-A) and target region preimplantation genetic testing for monogenic disease (PGT-M) strategies.Methods:A couple who attended the Reproductive and Genetic Medicine Center of Dalian Women and Children′s Medical Center (Group) in 2024 were selected as the study subject. Upon the woman′s two pregnancies, ultrasound examination revealed fetal abnormalities, and CNV-seq based on low-depth whole genome sequencing revealed that both fetuses had carried a maternal 17p12 microduplication of approximately 1.43 Mb. Microduplication in this region has been associated with Charcot-Marie-Tooth disease type 1A. In view of the fact that the resolution of conventional PGT-A detection cannot meet the requirement of small fragment CNV analysis, and conventional PGT-M assay cannot directly determine the CNV, two detection schemes were adopted. On the one hand, PGT-A testing with 1 Mb resolution was performed on the embryo to directly determine whether it carries the above microduplication. At the same time, the couple and their fetus were subjected to chromosomal typing scheme for the 17p12 region to indirectly identify embryos carrying the risk chromosome for microduplication. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No: FEJT-KY-2025-51).Results:Three embryos were tested after the first PGT cycle, of which 1 was not carrying the pathogenic variant and was euploid, whilst the other 2 embryos were carrying the 17p12 microduplication, and 1 of them was aneuploid. After genetic counseling, the euploid embryo without the 17p12 microduplication was selected for transfer, and prenatal diagnosis based on amniotic fluid sample showed that the fetal chromosomal karyotype was normal and did not carry the 17p12 microduplication.Conclusion:The combined application of high-resolution PGT-A and PGT-M typing detection of the target region can effectively block family transmission of the CNVs of small fragments.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

OBJECTIVE: To block family transmission of a small fragment copy number variation (CNV) with combined 1 Mb resolution preimplantation genetic testing for aneuploidy (PGT-A) and target region preimplantation genetic testing for monogenic disease (PGT-M) strategies. METHODS: A couple who attended the Reproductive and Genetic Medicine Center of Dalian Women and Children's Medical Center (Group) in 2024 were selected as the study subject. Upon the woman's two pregnancies, ultrasound examination revealed fetal abnormalities, and CNV-seq based on low-depth whole genome sequencing revealed that both fetuses had carried a maternal 17p12 microduplication of approximately 1.43 Mb. Microduplication in this region has been associated with Charcot-Marie-Tooth disease type 1A. In view of the fact that the resolution of conventional PGT-A detection cannot meet the requirement of small fragment CNV analysis, and conventional PGT-M assay cannot directly determine the CNV, two detection schemes were adopted. On the one hand, PGT-A testing with 1 Mb resolution was performed on the embryo to directly determine whether it carries the above microduplication. At the same time, the couple and their fetus were subjected to chromosomal typing scheme for the 17p12 region to indirectly identify embryos carrying the risk chromosome for microduplication. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No: FEJT-KY-2025-51). RESULTS: Three embryos were tested after the first PGT cycle, of which 1 was not carrying the pathogenic variant and was euploid, whilst the other 2 embryos were carrying the 17p12 microduplication, and 1 of them was aneuploid. After genetic counseling, the euploid embryo without the 17p12 microduplication was selected for transfer, and prenatal diagnosis based on amniotic fluid sample showed that the fetal chromosomal karyotype was normal and did not carry the 17p12 microduplication. CONCLUSION The combined application of high-resolution PGT-A and PGT-M typing detection of the target region can effectively block family transmission of the CNVs of small fragments.
Humans ; Female ; DNA Copy Number Variations/genetics* ; Preimplantation Diagnosis/methods* ; Pregnancy ; Pedigree ; Genetic Testing/methods* ; Male ; Adult ; Aneuploidy ; Chromosomes, Human, Pair 17/genetics* ; China ; East Asian People

Objective To identify the key immune-related genes and potential drug targets of Krabbe disease by using neural stem cells(NSCs)derived from induced pluripotent stem cells(iPSCs)generated from patients with Krabbe disease.Methods 1)The transcriptome data of GLD-NSCs(GSE212512)was analyzed using GEO2R and Sangerbox;2)Differential expression genes(DEGs)related to immunity were identified through various methods;3)Functional enrichment and pathway analysis were performed using DAVID;4)The protein-protein interaction network was constructed and analyzed using STRING and Cytoscape;5)Key immune-related genes were deter-mined through topological analysis;6)Potential therapeutic drugs were screened using DGIdb and drug MAP data-bases;7)Molecular docking was performed using CB-DOCK2.Results 1)Sixty-one immune-related DEGs were identified in patient NSCs,with GDNF,EGF,KDR,FGF10,and MET being identified as key immune-related genes;2)Drug candidates with high binding affinity to these genes were identified,including gentamicin for GDNF,cetuximab for EGF,tivozanib for KDR,and capmatinib for MET.Conclusions The predictions suggest cetuximab,gentamicin,tivozanib,and capmatinib exhibit high binding affinity with EGF,GDNF,KDR,and MET,respectively,indicating their potential application value in GLD targeted therapy.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective:To block family transmission of a small fragment copy number variation (CNV) with combined 1 Mb resolution preimplantation genetic testing for aneuploidy (PGT-A) and target region preimplantation genetic testing for monogenic disease (PGT-M) strategies.Methods:A couple who attended the Reproductive and Genetic Medicine Center of Dalian Women and Children′s Medical Center (Group) in 2024 were selected as the study subject. Upon the woman′s two pregnancies, ultrasound examination revealed fetal abnormalities, and CNV-seq based on low-depth whole genome sequencing revealed that both fetuses had carried a maternal 17p12 microduplication of approximately 1.43 Mb. Microduplication in this region has been associated with Charcot-Marie-Tooth disease type 1A. In view of the fact that the resolution of conventional PGT-A detection cannot meet the requirement of small fragment CNV analysis, and conventional PGT-M assay cannot directly determine the CNV, two detection schemes were adopted. On the one hand, PGT-A testing with 1 Mb resolution was performed on the embryo to directly determine whether it carries the above microduplication. At the same time, the couple and their fetus were subjected to chromosomal typing scheme for the 17p12 region to indirectly identify embryos carrying the risk chromosome for microduplication. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No: FEJT-KY-2025-51).Results:Three embryos were tested after the first PGT cycle, of which 1 was not carrying the pathogenic variant and was euploid, whilst the other 2 embryos were carrying the 17p12 microduplication, and 1 of them was aneuploid. After genetic counseling, the euploid embryo without the 17p12 microduplication was selected for transfer, and prenatal diagnosis based on amniotic fluid sample showed that the fetal chromosomal karyotype was normal and did not carry the 17p12 microduplication.Conclusion:The combined application of high-resolution PGT-A and PGT-M typing detection of the target region can effectively block family transmission of the CNVs of small fragments.

Objective: To investigate fast food consumption behaviors among 4th and 5th grade primary school students in agricultural and pastoral areas in Qinghai Province, and to provide scientific basis for nutrition education and intervention measures for school age children in agricultural and pastoral areas. Methods: Using multi stage stratified cluster random sampling method, a total of 969 fourth and fifth grade students were selected from 10 primary schools in 4 counties and districts in 3 cities of Haidong City, Hainan Prefecture and Haixi Prefecture from Qinghai Province. Self administered questionnaires were used to investigate the fast food consumption behaviors of participants. Results: The proportions of senior primary school students in agricultural and pastoral areas of Qinghai Province who had consumed western fast food and traditioal fast food in the past week were 45.8% and 75.6%, respectively, with statistically significant differences ( χ 2=290.24, P <0.05). The times of traditional fast food consumption in the past week among boarding students were higher than that of non boarding students( Z =6.44,5.84, P <0.05). The main reasons for senior primary school students in agricultural and pastoral areas of Qinghai Province to choose to consume western fast food were that it was delicious (84.7%), nutritious (62.6%), clean and hygienic (57.4%), and a better environment (57.0%). The top 4 reasons for chousing Chinese fast food were yummy(83.8%),nutritious(82.8%),clean and healthy(67.4%),and good environment(53.5%). Among the surveyed primary school students, 64.7% believed that diet structure of Chinese fast food was reasonable, 43.0% believed that the nutritional value of Chinese fast food was high, and 39.4% believed that the energy content of western fast food was high. Conclusion Fast food consumption is a common dietary behavior of senior primary school students in agricultural and pastoral areas of Qinghai Province. Relevant departments should strengthen the nutrition education related to fast food, promote the dissemination of health knowledge, enable students to develop a good lifestyle and reduce fast food consumption.

Objective: To study the consumption of beverages among senior primary school students in rural and pastoral areas of Qinghai Province, China, in order to provide evidence for the development of nutrition and intervention strategies. Methods: A multi stage stratified cluster random sampling method was employed to select 969 primary school students in grades 4 and 5 from 10 schools in Hainan Autonomous Prefecture, Haixi Autonomous Prefecture and Haidong City. All participants completed a questionnaire survey on daily beverage consumption. The Chi square test was performed to compare differences in reported rates of beverage consumption among students in different groups. Results: The proportion of students who consumed beverages at home, school and elsewhere were 96.9%, 64.5% and 84.9%, respectively. The most popular beverages consumed at home were milk and yogurt ( 63.1 %), tea water (53.0%), and tea drinks (52.4%). The most popular beverages consumed at school were tea(29.8%), milk and yogurt (27.8%) and tea drinks (18.4%), while the most popular beverages consumed in other places were tea drinks ( 42.0 %), carbonated drinks (38.1%) and milk and yogurt (35.0%). The top five reasons for choosing a given beverage were taste delicious (81.2%), nutritious (57.6%),healthy and clean(52.6%),many students like to drink(39.6%),family members often drink(37.7%). Conclusion The consumption of beverages was popular among students, and sugared beverages represented a large proportion of the beverages consumed. Therefore, there is an urgent need to improve the food environment and provide effective nutrition education for students, so as to encourage the consumption of healthy beverages and cultivate healthy eating behaviors.

Objective: To understand the current situation regarding snack food consumption among grade 4 and grade 5 primary school students in agricultural and pastoral areas of Qinghai Province, China, and to provide a scientific basis for nutrition education and intervention strategies. Methods: Multistage stratified cluster random sampling was employed. The research included 969 fourth and fifth grade students were selected from 10 primary schools in four counties and districts of three cities in Haidong City, Hainan Prefecture and Haixi Prefecture in Qinghai Province. The self report questionnaire method was used to investigate the current status regarding snack food consumption in this population. Results: The proportion of students who consumed snack food at home, school and elsewhere were 98.2%, 88.5% and 75.4%, respectively. Male students reported a lower rate of snack consumption at school than female students ( χ 2=9.66). The fifth grade students reported a higher rate of snack consumption at home and other places than the fourth grade students ( χ 2=10.31, 6.77). The reported rate of snack consumption of students in the rural was higher than that in the county( χ 2=6.03,100.53, 24.77). The reported rate of snack consumption of boarding students at home was lower than that of non-boarding students ( χ 2=7.22), while the reported rate of snack consumption at school was higher than that of non-boarding students ( χ 2=9.04）（ P <0.01). The most popular snacks consumed at home included fruits and vegetables, cereals and nuts (76.9%, 67.2%, 63.7%), while the most popular snacks consumed at school were fruits and vegetables, cereals and candies (45.1%, 36.9%, 24.4%). The most popular snacks consumed in other settings included ice cream, candies and beverages(54.7%, 51.6%, 42.9%). The top three reasons for snacking were that snacks were regarded as delicious, healthy/nutritious and clean (76.9%, 65.5% and 59.0%, respectively). Conclusion Snacking is popular among students, although many snacks are unhealthy. Therefore, there is a need to improve food environments and nutrition education, so as to help students to choose healthy beverages and adopt healthy eating behaviors.