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 evaluate the effect of ultrasound-guided internal branch block of superior laryngeal nerve on stress response during endotracheal catheter indwelling in patients undergoing uvulopalatopharyngoplasty (UPPP).Methods:A total of 80 patients with severe obstructive sleep apnea syndrome requiring elective UPPP from the Hunan Provincial People′s Hospital from January 2020 to December 2021 were retrospectively selected and divided into nerve block group (group B) and dexmedetomidine group (group D). Patients in group B and D received general anesthesia. Patients in the group B received bilateral internal branch block of superior laryngeal nerve under ultrasound guidance before postoperative recovery. Patients in the group D received dexmedetomidine intravenously before the end of surgery. The cough scores and mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E) and norepinephrine (NE) levels of patients before anesthesia (T 1), immediately after recovery (T 2), 2 h after recovery (T 3), 6 h (T 4), and 12 h (T 5) during endotracheal catheterization were recorded in both groups. The Visual Analogue Scale (VAS) scores of T 2, T 3, T 4, T 5 and 24 h after surgery (T 6) were also obtained. Results:Compared with group D, the cough scores of the group B patients were significantly lower, and the number of cases requiring remedial analgesia was significantly less (all P<0.01). Compared with T 1, MAP and HR at T 2-T 5 time points in the group B and HR and MAP at T 2-T 5 time points in the group D were significantly increased (all P<0.05). Compared with the group D, MAP and HR were significantly higher than those at each time point of T 2-T 5 in the group B (all P<0.05). Compared with T 1, the serum NE and E levels in the group D at T 2-T 5 time points, and the serum NE and T 2 E levels in the group B at T 2-T 5 time points were increased, and the differences were statistically significant (all P<0.05). Compared with the group D, serum E and serum NE levels at T 2-T 5 and T 2-T 4 in the group B were significantly lower (all P<0.05). Compared with T 2, T 5-T 6 VAS scores in the group B and T 3-T 6 VAS scores in the group D were significantly decreased (all P<0.05). Compared with the group D, the VAS scores at T 2-T 5 time points in the group B were significantly lower (all P<0.05). Conclusions:Compared with intravenous use of dexmedetomidine, ultrasound-guided internal branch block of superior laryngeal nerve can significantly reduce the discomfort and stress response during catheterization after UPPP, increase the comfort level of patients, reduce the incidence of postoperative complications, and promote rapid recovery of patients.

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.

Objective:To evaluate the effect of ultrasound-guided internal branch block of superior laryngeal nerve on stress response during endotracheal catheter indwelling in patients undergoing uvulopalatopharyngoplasty (UPPP).Methods:A total of 80 patients with severe obstructive sleep apnea syndrome requiring elective UPPP from the Hunan Provincial People′s Hospital from January 2020 to December 2021 were retrospectively selected and divided into nerve block group (group B) and dexmedetomidine group (group D). Patients in group B and D received general anesthesia. Patients in the group B received bilateral internal branch block of superior laryngeal nerve under ultrasound guidance before postoperative recovery. Patients in the group D received dexmedetomidine intravenously before the end of surgery. The cough scores and mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E) and norepinephrine (NE) levels of patients before anesthesia (T 1), immediately after recovery (T 2), 2 h after recovery (T 3), 6 h (T 4), and 12 h (T 5) during endotracheal catheterization were recorded in both groups. The Visual Analogue Scale (VAS) scores of T 2, T 3, T 4, T 5 and 24 h after surgery (T 6) were also obtained. Results:Compared with group D, the cough scores of the group B patients were significantly lower, and the number of cases requiring remedial analgesia was significantly less (all P<0.01). Compared with T 1, MAP and HR at T 2-T 5 time points in the group B and HR and MAP at T 2-T 5 time points in the group D were significantly increased (all P<0.05). Compared with the group D, MAP and HR were significantly higher than those at each time point of T 2-T 5 in the group B (all P<0.05). Compared with T 1, the serum NE and E levels in the group D at T 2-T 5 time points, and the serum NE and T 2 E levels in the group B at T 2-T 5 time points were increased, and the differences were statistically significant (all P<0.05). Compared with the group D, serum E and serum NE levels at T 2-T 5 and T 2-T 4 in the group B were significantly lower (all P<0.05). Compared with T 2, T 5-T 6 VAS scores in the group B and T 3-T 6 VAS scores in the group D were significantly decreased (all P<0.05). Compared with the group D, the VAS scores at T 2-T 5 time points in the group B were significantly lower (all P<0.05). Conclusions:Compared with intravenous use of dexmedetomidine, ultrasound-guided internal branch block of superior laryngeal nerve can significantly reduce the discomfort and stress response during catheterization after UPPP, increase the comfort level of patients, reduce the incidence of postoperative complications, and promote rapid recovery of patients.

Objective : To compare the antiviral efficacy and renal safety of nucleoside analogs(NAs) monotherapy versus combination therapy in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients with high viral load. Methods : This study enrolled a total of 353 treatment-naïve HBeAg-positive chronic hepatitis B (CHB) patients with high viral load , the treatment regimen was divided into 5 groups , consisting of 4 monotherapy groups and 1 combination therapy group as follows : 88 cases in the Entecavir (ETV) group , 135 cases in the Teno- fovir Disoproxil Fumarate (TDF) group , 34 cases in the Tenofovir Alafenamide Fumarate (TAF) group , 25 cases in the Tenofovir Amibufenamide (TMF) group , and 71 cases in the ETV combined with TDF (ETV + TDF) group . A retrospective cohort study design was adopted to analyze HBV DNA levels , serological indicators ( HBsAg and HBeAg levels) , renal function indicators ( serum Scr levels , eGFR) at 24 and 48 weeks of treatment across various groups , as well as the HBsAg clearance rates , HBeAg seroconversion rates and HBV DNA suppression rates (HBV DNA < 20 IU/ml) at 48 weeks across the groups . Multivariate logistic regression analysis was conducted to identify the influencing factors for HBV DNA suppression . Results : At 24 weeks , the HBV DNA level in the ETV + TDF selected . Key miRNAs included hsa-let-7b-5p , hsa-let-7c-5p , hsa-let-7b-3p _ 1ss22CT , and hsa-miR-199b-5p , with BACH1 and IFNAR1 identified as their shared target genes . GO analysis revealed that the enriched target genes were primarily involved in protein binding , metal ion binding , transferase activity , DNA binding , transcriptional regulation by RNA polymerase Ⅱ , and nucleotide binding. KEGG pathway analysis indicated that the target genes were mainly associated with metabolic pathways , cancer-related pathways , the PI3K-Akt signaling pathway , and the Rap1 signaling pathway . Conclusion Differential expression of miRNAs in amniotic fluid exosomes was ob- served between DS fetuses and those with normal karyotypes . Combined analysis with placental miRNAs revealed hsa-miR-199b-5p as a common differentially expressed miRNA in both DS amniotic fluid and placenta. It is hypoth- esized that BACH1 and IFNAR1 , shared target genes of hsa-miR-199b-5p , hsa-let-7b-5p , hsa-let-7c-5p , and hsa- let-7b-3p_1ss22CT , may play a role in the pathogenesis of DS .

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

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.

Objective:This study starts from the main problems existing in the current stage of the development of pediatric clinical research in China and focuses on the construction of a clinical research management system. By innovating the platform management model and enhancing personnel skills, we can provide support and assurance for improving the clinical research platform and its sustainable development in the future.Methods:This study established an integrated management platform for Industry-Sponsored Initiated Clinical Research Trial (IST) and Investigator Initiated Clinical Research (IIT) and implement integrated management of IST and IIT projects. At the same time, in response to the weak links in quality management, synchronous training of management and research talents should be implemented to achieve dual improvement in project management quality and platform service efficiency throughout the process.Results:We had optimized the clinical research organization structure, improved the management system, and strengthened the quality supervision of IIT projects by establishing rules and systems to improve the quality and efficiency of project management.Conclusions:Based on analyzing the current situation in China and referring to international experience, we have built a clinical research management platform in line with the development of the hospital, and implemented centralized management of the entire process of IST and IIT projects, strengthened project process quality control, which is expected to provide a reference for peers.

Objective To explore the status and trajectory of urinary incontinence in patients with bladder cancer after orthotopic neobladder surgery,and analyze the characteristics of different trajectory categories,to provide references for the intervention and management of urinary incontinence in patients after orthotopic neobladder surgery.Methods A prospective study design was adopted,and the convenience sampling was used to select 142 eligible patients who underwent in orthotopic neobladder surgery in a tertiary hospital from January 2019 to August 2022.Demographic and clinical data of the patients were collected.The continence status of patients was evaluated by the International Consultation on Incontinence Questionnaire-Short Form(ICI-Q-SF)at 1 month after surgery,3 months after surgery,6 months after surgery and 1 year after surgery.Additionally,postoperative physical condition scores,pelvic floor muscle training,and timed urination information were collected.The Group-Based Trajectory Model was used to identify the development trajectory of urinary incontinence,and the logistic regression was conducted to identify influencing factors of urinary incontinence trajectories.Results 142 cases were included.There are 3 distinct daytime and nocturnal incontinence trajectory groups that were respectively identified:the significantly improved group(21.83％,29.58％),the slowly alleviated group(52.82％,48.59％),and the risk fluctuation group(25.35％,21.83％).Multivariate logistic regression analysis indicated that age,preservation of neurovascular bundles,and adherence to timed voiding were factors significantly influencing urinary incontinence trajectory categories(P＜0.05).Conclusion The trajectory of urinary incontinence in patients undergoing orthotopic neobladder surgery showed an overall improvement trend within a year,with group differences.Clinical attention should be paid to the dynamic evaluation of postoperative urinary incontinence in older,unreserved nerves,and those who did not adhere to scheduled urination,and a phased matching postoperative rehabilitation plan should be developed to improve the urinary control level of patients.

Objective To investigate the neuroprotective effect of TGP on PS rats and determine the impact on the Ste20-like proline/alanine-rich kinase/Na+-K+-Cl cotransport(SPAK/NKCC1)signaling pathway.Methods After PS model was successfully established in 60 male SD rats(7 weeks old),they were randomly divided into model group,low-and high-dose TGP groups,high-dose TGP+negative control group,and high-dose TGP+WNK3 overexpression group,with 12 rats in each group.Another 12 healthy rats served as the control group.After modeling,50 or 200 mg/kg TGP was given to the rats of corresponding groups intragastrically,the overexpression plasmids of WNK3 were given to the rats from the high-dose TGP+WNK3 overexpression group through tail vein injection,and same volume of normal saline was given to the control group.All of these agents were administrated once per day for 7 consecutive days.ELISA was applied to de-tect serum levels of IL-6,IL-1β,MDA and SOD.HE staining was applied to detect the pathological morphology of the substantia nigra region in brain tissue.TUNEL staining was used to observe neuronal apoptosis.Immunohistochemistry was conducted to measure the expression of α-synucle-in(α-syn),and Western blotting for the expression of Bax,Bcl-2 and SPAK/NKCC1 signaling pathway related proteins(WNK3,p-SPAK,SPAK,p-NKCC1 and NKCC1).Results Compared with the model group,the pathological damage of neurons in substantia nigra was reduced in low-and high dose TGP groups,reduced contents of IL-6,IL-1β and MDA,lower neuronal apoptotic rate,and declined expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,but raised SOD content and Bcl-2 expression level(88.39±8.96 U/mg,119.57±12.01 U/mg vs 60.28±6.14 U/mg,P＜0.05;0.57±0.06,0.82±0.09 vs 0.38±0.04,P＜0.05).The intervention with WNK3 overexpression resulted in more severe pathological damage to neurons in the sub-stantia nigra,increased contents of IL-6,IL-1β and MDA,higher neuronal apoptotic rate,enhanced expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,and reduced SOD con-tent and Bcl-2 expression level when compared with the high-dose TGP+negative control group(P＜0.05).Conclusion TGP exerts neuroprotective effects on PS rats,and its mechanism is re-lated to the inhibition of the SPAK/NKCC1 signaling pathway.