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

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*

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 investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Tuberculosis,as a chronic infectious disease caused by Mycobacterium tuberculosis(MTB)infection,presenting a serious threat to human and animal health.When human body is infected by MTB,it quickly initiates an immune response,in which T lymphocyte-mediated cellular immunity plays a key role,as it can effectively recog-nize and eliminate MTB,serving as an important defense line for the body against MTB.However,during MTB in-fection process,myeloid-derived suppressor cells(MDSCs)undergo amplification and activation,which exhibit in-hibitory effect on the immune function of T lymphocytes and interfere the normal immune response of the body,making MTB easier to survive and reproduce in the body.This article discusses the role of MDSCs in the occu-rrence,development and prognosis of tuberculosis from two different perspectives,expects to provide new perspec-tives and ideas for the immunotherapy of tuberculosis as well as the research and development of targeted drugs,so as to open up a new way for the prevention and treatment of tuberculosis.

Objective:To evaluate the preventive effect of an antimicrobial peptide spray on chemoradiotherapy-induced oral mu-cositis in patients with hematologic malignancies.Methods:From December 2021 to July 2023,a total of 191 newly diagnosed pa-tients with hematologic malignancies undergoing concurrent chemoradiotherapy at our hospital were included in the study.Patients were divided into a treatment group(n=124,received antimicrobial peptide spray)and a control group(n=67,received placebo spray).All patients underwent standardized chemoradiotherapy regimens and oral care.Outcomes compared between groups includ-ed the incidence and severity of oral mucositis,ulcer healing time,pain scores,antibiotic usage,inflammatory markers[C-reactive protein(CRP),procalcitonin(PCT)],duration of neutropenia,adverse events,and quality of life.Results:The incidence of oral mucositis in the treatment group was significantly lower than in the control group(12.90％vs.31.34％,P＜0.05),with a relative risk reduction(RRR)of 58.84％,absolute risk reduction(ARR)of 18.44％,and a number needed to treat(NNT)of 5.423.The treatment group showed shorter ulcer healing time,lower pain scores,reduced antibiotic usage and intensity,lower mean levels of CRP and PCT,and a shorter duration of neutropenia.The incidence of exacerbated local pain and drug-related adverse reactions was also significantly lower in the treatment group,compared to the control group(P＜0.05),with no evident systemic toxicity ob-served.Patients in the treatment group reported higher quality of life and satisfaction scores(both P＜0.05).Conclusion:The an-timicrobial peptide spray effectively reduces the incidence and severity of chemoradiotherapy-associated oral mucositis,mitigates in-flammation and infection risk,and improves quality of life.

Objective:To investigate the effect of p38MAPK signaling pathway mediating progesterone regulation on IL-8 protein secretion by decidual stromal cells(DSCs)on early spontaneous miscarriage.Methods:IHC and Western blot were applied to detect protein expressions of p38MAPK and p-p38MAPK in decidual tissues of miscarriage group and control group.Human DSCs in early pregnancy were isolated in vitro and cultured to be treated with different concentrations of progesterone(0.01 μmol/L,0.1 μmol/L,1 μmol/L and 10 μmol/L),with ELISA measuring IL-8 protein secretion from DSCs and Western blot measuring protein expressions of p38MAPK and p-p38MAPK in DSCs.After treatment with p38MAPK inhibitor SB203580,IL-8 protein secretion was detected by ELISA in progesterone+inhibitor group,progesterone group and control group.Results:Protein expression of p-p38MAPK in decidual tissues of miscarriage group was significantly higher than that of control group(P=0.002 3).Protein secretion of IL-8 in DSCs of 0.01 μmol/L progesterone group was lower than that of control group(P=0.027 6),protein expression of p-p38MAPK in DSCs of 0.1 μmol/L proges-terone group was lower than that of control group(P=0.025 3),IL-8 protein expression was significantly lower than that in control group(P=0.007 0),and protein expressions of both IL-8 and p-p38MAPK from DSCs in 1 μmol/L and 10 μmol/L progesterone groups were significantly lower than those in control group(P=0.003 2,P=0.001 9;P=0.002 2,P=0.001 3).IL-8 protein secretion in proges-terone+p38MAPK inhibitor group was further reduced compared to progesterone group(P=0.046 6).Conclusion:Abnormal activation of p38MAPK signaling pathway is involved in early spontaneous miscarriage,and progesterone may down-regulate IL-8 expression in DSCs by inhibiting p38MAPK phosphorylation to correct early spontaneous miscarriage caused by Th1/Th2 cytokine imbalance.