OBJECTIVE: Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance. METHODS: A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09). RESULTS: CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband. CONCLUSION As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.
Female ; Humans ; Male ; Pregnancy ; Abortion, Habitual/genetics* ; DNA Copy Number Variations ; Karyotyping/methods* ; Preimplantation Diagnosis ; Translocation, Genetic

OBJECTIVES: To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types. METHODS: We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up. RESULTS: Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence. CONCLUSIONS Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.

Objective:To analyze the assessment value of the quantitative parameters of coronary computed tomography angiography(CCTA)combined with QRS wave complex of electrocardiogram(ECG)for grading of cardiac function in patients with coronary heart disease(CHD).Methods:Eighty CHD patients admitted to Beijing Rehabilitation Hospital,Capital Medical University between January 2023 and December 2024 were selected.The grading of cardiac function of CHD patients were assessed according to the standard of New York Heart Association(NYHA).All patients underwent CCTA and ECG upon admission.CCTA quantitative parameters and QRS wave complex duration were recorded and compared among patients with different grades of cardiac function.The correlation between CCTA quantitative parameters[non-calcified plaque volume(NCPV),calcified plaque volume(CPV),total plaque volume(TPV),vessel volume,reconstruction index],QRS wave complex duration,and grading of cardiac function of CHD patient was analyzed.The area under curve(AUC)of receiver operating characteristic(ROC)curve was used to analyze the value of each parameter and QRS wave complex duration in assessing CHD patients whose cardiac function grade was≥III grade.Results:In the 80 CHD patients,NYHA grades were distributed as follows:11 cases were grade I,and 23 cases were grade II,and 27 cases were grade III,and 19 cases were grade IV.The NCPV,CPV,TPV,reconstruction index,and QRS wave complex duration of patients at grade III and grade IV were higher than those of patients at grade I-grade II,and the differences were significant(F=17.401,37.077,12.297,7.087,11.148,P<0.05).Furthermore,patients at grade IV showed higher values in all parameters than those of patients at grade III.The NCPV,CPV,TPV,reconstruction index(t=3.486,4.315,3.444,2.068,2.600,P<0.05),and QRS wave complex duration of CCTA parameters showed positive correlations with cardiac function grading in CHD patient(r=0.464,0.548,0.346,0.287,0.373,P<0.05).ROC curve analysis revealed that the AUC values of alone NCPV,CPV,TPV,reconstruction index,QRS wave complex duration of CCTA parameters,and the combination of these indicators were respectively 0.793,0.843,0.723,0.748,and 0.737 in assessing CHD patients whose cardiac function grade was≥III,which indicated that these indicators had a certain assessment value,and the combined detection can improve the AUC value and sensitivity.Conclusion:The combination of CCTA parameters(NCPV,CPV,TPV,reconstruction index)and QRS wave complex duration can improve the assessment value for CHD patients whose grade of cardiac function is≥grade III.

Objective:To investigate predictive value of dynamic electrocardiogram heart rate variability(HRV)combined with three-dimensional spot tracking echocardiography(3D-STE)for postoperatively major adverse cardiovascular events(MACE)in patients with coronary heart disease(CHD).Methods:The clinical data of 80 CHD patients,who underwent percutaneous coronary intervention(PCI)treatment at Beijing Rehabilitation Hospital affiliated with Capital Medical University from January 2022 to December 2023,were retrospectively collected.All patients underwent dynamic electrocardiogram HRV and 3D-STE examination before surgery,and 1-year follow-up.The condition of occurring MACE during the follow-up period was analyzed as statistical method,and the patients were divided into occurrence group(21 cases)and non-occurrence group(59 cases).The relevant parameters of dynamic electrocardiogram HRV and 3D-STE examination of occurring MACE of CHD patients between two groups were compared,and the predictive value of dynamic electrocardiogram HRV combined with 3D-STE examination for postoperative MACE of CHD patients was analyzed.Results:In 80 CHD patients,21 cases occurred postoperative MACE,with an incidence rate of 26.25%.The standard deviation of the average NN intervals(SDANN)(65.26±9.65)ms of 5-minute sinus,the standard deviation of normal-to-normal intervals index(SDNN Index)(40.15±6.36)ms of 5-minute in continuous 24 hours,the root mean square of successive differences(r-MSSD)(36.86±4.55)ms between the normal adjacent cardiac cycles,the left atrial emptying fraction(LAEF)(40.25±4.53)%,and the left atrial storage phase strain(LASr)(15.24±3.62)%in CHD patients with MACE were lower than those without MACE[(87.45±10.22)ms,(52.45±7.85)ms,(46.54±6.25)ms,(48.54±6.33)ms,(19.99±4.55)%],and the left atrial pre-contraction volume(LAVp)(42.51±3.65)ml was higher than that(35.18±2.99)mL in patients without MACE,with statistically significant differences(t=8.666,6.457,6.499,9.093,5.510,4.317,P<0.05).Logistic regression analysis showed that SDANN,SDNN Index,r-MSSD,LAVp,LAEF,LASr were correlations with the occurrence of postoperative MACE in CHD patients(OR=0.756,0.772,0.694,2.481,0.721,0.739,P<0.05).The receiver operating characteristics(ROC)curves indicated that the area under curve(AUC)values of SDANN,SDNN Index,r-MSSD,LAVp,LAEF and LASr were all greater than 0.70 in predicting postoperative MACE in CHD patients,which indicated all of them had predictive value,and the predictive value of the combined detection was higher.Conclusion:Dynamic electrocardiogram HRV and 3D-STE parameters have a certain predictive value for the occurrence of postoperative MACE in CHD patients,and the predictive value of the combined detection for the them are higher.Therefore,dynamic electrocardiogram HRV and 3D-STE parameters can be used as one of the important reference schemes of assessing postoperative MACE of patients.

Objective:To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and chronic idiopathic intestinal pseudo-obstruction (CIIPX).Methods:A pedigree presented at the First Hospital of Lanzhou University in June 2024 for CVDPX combined with CIIPX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15).Results:Both the proband and his affected younger brother were found to harbor a hemizygous c. 443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded by the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+ PS4+ PP2+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. Conclusion:This study confirmed the diagnosis of CVDPX/CIIPX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.

OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis （UC） and ankylosing spondylitis （AS） who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined， using Naranjo’s Scale， that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab， the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib， the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment， the patient’s symptoms were significantly alleviated， and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions， evaluation of treatment responses， and optimization of drug regimens， they assisted the physicians in formulating an individualized medication plan， ensuring the safety and efficacy of the patient’s medication use.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

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OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To explore the mechanism and clinical manifestations of a case with complex structural variations involving chromosomes 5, 7, and 14, and assess the value of Chromosome conformation-based karyotyping (C-MoKa) for its diagnosis. METHODS: Two half-sibs by the same father presented at the First Hospital of Lanzhou University in December 2024 for severe multi-system abnormalities were selected as study subjects. Peripheral blood samples from the their parents were subjected to conventional chromosomal karyotyping analysis. The father was further analyzed using C-MoKa, while both siblings underwent copy number variation sequencing (CNV-seq). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-05). RESULTS: Conventional karyotype analysis indicated that the father has a karyotype of 46,XY,add(5)(p15.3). CNV-seq identified multiple chromosomal abnormalities in both siblings, including duplications and deletions of chromosomes 14 and 5. C-MoKa analysis further revealed a complex chromosomal structural variation involving chromosomes 5, 7, and 14 in the father. These variations were closely associated with the severe phenotypes noted in both children. CONCLUSION Complex chromosomal structural variations can lead to multi-system abnormalities and significantly impact reproductive health. Compared to conventional karyotyping, the C-MoKa technique has shown significant advantage in identifying such complex rearrangements. The combined application of multiple techniques can improve the accuracy of diagnosis, enabling genetic counseling for carriers to reduce their risk for producing further affected offspring.
Female ; Humans ; Male ; China ; Chromosome Aberrations ; DNA Copy Number Variations/genetics* ; Karyotyping ; Pedigree ; East Asian People/genetics*