Objective:To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband.Methods:A Chinese pedigree which opted elective abortion at the Women and Children′s Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). Results:Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c. 7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c. 1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. Conclusion:This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.

Objective:To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification.Methods:A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78).Results:The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband′s father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+ PM2_Supporting+ PP2+ PP3+ PP4). Conclusion:The heterozygous c. 728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c. 728C>T variant of the TUBB8 gene, oocyte donation may be considered.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

OBJECTIVE: To explore the genetic basis for a woman with oocyte maturation disorder during assisted reproductive treatment (ART), and to verify the source of the variant and its impact on oocyte maturation through family verification. METHODS: A 35-year-old infertile woman presented at the Reproductive Medicine Center of Gansu Provincial Maternal and Child Health Care Hospital on 20 October 2023 for a 10-year history of infertility despite unprotected intercourse was selected as study subject. Peripheral venous blood sample was collected from the proband. Next-generation sequencing (NGS) was used to detect the potential variant. Candidate variants were validated within her family by Sanger sequencing, and their deleteriousness was assessed with comprehensive bioinformatic analyses to elucidate their origin and impact on oocyte maturation. According to the Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as ACMG Guidelines) formulated by the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Gansu Provincial Maternal and Child Health Care Hospital (Ethics No.: 2023GSFYLS78). RESULTS: The proband underwent three controlled ovarian-stimulation cycles as part of assisted reproductive technology, yielding a total of 29 oocytes, among which only three were mature, whilst the remainders exhibited maturation arrest. Targeted sequencing of peripheral-blood DNA revealed a heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene. While the same variant was detected in the proband's father. Based on the ACMG guidelines, the variant was classified to be likely pathogenic (PS4_Supporting+PM2_Supporting+PP2+PP3+PP4). CONCLUSION The heterozygous c.728C>T (p.P243L) missense variant of the TUBB8 gene probably underlay the oocyte maturation disorder in the proband, which may be either autosomal dominant or autosomal recessive. For probands with oocyte maturation disorders caused by the heterozygous c.728C>T variant of the TUBB8 gene, oocyte donation may be considered.
Humans ; Female ; Adult ; Mutation, Missense ; Oocytes/metabolism* ; Heterozygote ; Tubulin/genetics* ; Infertility, Female/genetics* ; High-Throughput Nucleotide Sequencing ; Pedigree

Objective:To construct and validate a nomogram prediction model for the recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography (ERCP) in patients with common bile duct stones.Methods:The clinical data of 515 patients with common bile duct stones treated in Yancheng First People's Hospital from January 2018 to December 2022 were retrospectively analyzed, including 273 males and 242 females, aged (65.5±12.1) years. According to the ratio of 8∶2, all cases were randomly divided into a training set ( n=412) and a validation set ( n=103). According to whether common bile duct stones recurred after ERCP, 412 patients in the training set were divided into two groups: the recurrence group ( n=72) and the non-recurrence group ( n=340). The patients' gender, age, length and diameter of stones, number of stones, diameter of common bile duct and other clinical data were recorded. The logistic regression model was used to analyze the risk factors of recurrence, and a nomogram was constructed based on the analysis results. The concordanceindex, area under the receiver operating characteristic (ROC) curve and calibration chart were used to evaluate the model. Bootstrap self sampling method was used to internally verify the prediction model. Results:The recurrence rate of common bile duct stones in the training set was 17.5% (72/412). Multivariate logistic regression analysis showed that stone length, stone number, mixed stones, periampullary diverticulum, postoperative cholecystectomy, nipple incision were risk factors for recurrence of common bile duct stones after ERCP (all P<0.05). Small incision of nipple assisted with large balloon dilatation, incision of nipple titanium splint synthesis, and postoperative ursodeoxycholic acid were protective factors for recurrence of common bile duct stones after ERCP (all P<0.05). The concordance index of the nomogram model based on the above influencing factors was 0.791(95% CI: 0.633-0.892), and the area under the ROC curve for predicting postoperative recurrence of common bile duct stones in the training set and the validation set were 0.905(95% CI: 0.819-0.987) and 0.873(95% CI: 0.809-0.935), respectively. The calibration curve was basically consistent with the ideal curve, and the concordanceindex of internal validation was 0.781(95% CI: 0.628-0.874). Conclusion:The nomogram model based on the influencing factors of common bile duct stone recurrence can predict the risk of common bile duct stone recurrence after ERCP.

Objective To observe the value of T2 mapping for quantitatively evaluating the changes of junctional zone and outer myometrium caused by endometrial fibrosis.Methods A total of 73 infertility patients with endometrial fibrosis confirmed by hysteroscopy(disease group)and 33 healthy women of childbearing age(control group)were prospectively enrolled,and MR examinations were performed at the late proliferative phase of endometrium.The thickness and T2 value of junctional zone,T2 value of outer myometrium on anterior,posterior and fundus wall of midsagittal corpus uteri were measured,and the mean value of the above measurements on the three walls were calculated.Receiver operating characteristic curves were constructed,the areas under the curves(AUC)were calculated to explore the efficacy of those with significant difference among the mean thickness and the mean T2 value of junctional zone,the mean T2 value of outer myometrium and their combination for evaluating endometrial fibrosis.Results The thickness and T2 value of anterior wall,posterior wall,fundus wall and the mean junctional zone in disease group were all significantly higher than those in control group(all P＜0.001).No significant difference of T2 value of anterior wall,posterior wall,fundus wall nor the mean outer myometrium was found between groups(all P＞0.05).The mean thickness and the mean T2 value of junctional zone and their combination could be used to effectively evaluate endometrial fibrosis,with AUC of 0.839,0.822 and 0.922,respectively,and their combination had the best performance(both P＜0.01).Conclusion T2 mapping could be used to quantitatively evaluate the injury of junctional zone caused by endometrial fibrosis.

Objective:To explore the lived experiences of family members of terminal ICU patients regarding their humanistic care needs and provide theoretical foundations for developing nursing care plans tailored to their needs.Methods:This study was a descriptive qualitative study. From April to December 2023, 16 family members of terminally ill ICU patients in Shanghai East Hospital, Tongji University were selected for semi-structured interviews using purposive sampling method, and the interview data were qualitatively analyzed using Colaizzi 7-step analysis.Results:The humanistic care needs of family members of terminally ill ICU patients can be categorized into five themes, namely, the need to know the condition at the first time; the need to participate in treatment and decision-making; the need to respect the wishes of terminally ill patients; the need for psychological care; and the need for social support.Conclusions:The humanistic care needs of family members of terminal ICU patients remain largely unmet. Nursing professionals should consider these needs and preferences and provide family members with professional guidance to help them establish positive coping mechanisms.

Objective:To evaluate the early efficacy and safety of transnasal endoscopic surgical resection of orbital cavernous hemangioma (OCH) at orbital resection by intranasal technique (ORBIT) stage Ⅲ.Methods:A retrospective study was conducted on 20 patients (20 eyes) who underwent nasal endoscopic surgery to remove ORBIT stage Ⅲ OCH at the Third Hospital of Peking University from July 2021 to July 2024. The cohort were included 10 males and 10 females, aged from 25 to 59 years, with a mean follow-up time of (5.10±4.51) months. Preoperative symptoms included visual field defects in 19 patients (95%), decreased visual acuity in 18 patients (90%), exophthalmos in 2 patients (10%), diplopia in 2 patients (10%), headache in 2 patients (10%), ocular pain in 2 patients (10%), and color vision abnormalities in 1 patient (5%). Data on patient demographics, medical history, imaging data, surgical approach, and postoperative outcomes were collected. Pre-and post-surgical outcomes including best corrected visual acuity (BCVA), visual field, proptosis, and intraocular pressure were compared. Surgical approaches included transnasal endoscopic OCH resection (12 cases, 60%) and transnasal endoscopic combined conjunctival approach OCH resection (8 cases, 40%). The results of the postoperative 2-week review were used as the postoperative short-term efficacy data, and those at 3 months were used for postoperative therapeutic efficacy analysis. SPSS 26.0 statistical software was applied for statistical analysis.Results:In 20 patients, all OCH were completely resected, and the BCVA, visual field, and exophthalmos were significantly improved post-operatively. The differences were statistically significant before and after surgery ( t values were 3.169, 5.127, and 3.350, respectively, all P<0.05). There were no serious complications in the short term after surgery. The short-term complications after endoscopic surgery alone were mainly new-onset diplopia in 1 case (1/12), and the short-term complications after combined approach were new-onset diplopia in 5 cases (5/8) and pupil dilation in 2 cases (2/8). All short-term complications recovered within 3 months, and no serious or permanent complications occurred in the long-term follow. Conclusion:The endoscopic transnasal surgery is a safe and effective approach for complete resection of ORBIT stage Ⅲ OCH, with promising early results.

Objective:To investigate the current status and influencing factors of decision anxiety in guardians of children with acute appendicitis under Endoscopic retrograde appendicitis therapy (ERAT) background, and to provide reference for the development of targeted intervention programs for decision anxiety.Methods:Convenient sampling method was used to select 254 guardians of children with acute appendicitis treated in the Department of Pediatrics, Second Affiliated Hospital of PLA Air Force Medical University from February 2023 to April 2024. A cross-sectional survey was conducted using the General Data Questionnaire, the State-Trait Anxiety Inventory Form Y-State anxiety subscale and the Preparation for Decision Making Scale. Multiple linear regression was used to analyze the influencing factors in guardians of children with acute appendicitis.Results:Among the guardians of 254 children with acute appendicitis, 156 were males and 98 were females, aged (37.44 ± 3.63) years old. The decision anxiety score of guardians of children with acute appendicitis was (52.49 ± 6.54). The results of multiple linear regression showed that age of children, gender of guardian, education level of guardian, per capita monthly income of family, decision making tendency and decision preparation were the main influencing factors of decision anxiety in guardians of children with acute appendicitis ( t values were -7.07-3.58, all P<0.05), which could explain 64.4% of the total variation. Conclusions:The decision anxiety in guardians of children with acute appendicitis is at a high level. Medical staff should provide targeted decision guidance, improve decision assistance programs and provide more effective decision support for guardians of children with acute appendicitis.

Objective:To investigate the difference between routine pulmonary ventilation function test (PFT) and impulse oscillometry (IOS) in children with bronchial asthma (BA) control and children without BA control.Methods:A total of 165 BA children admitted to the Shenzhen Longhua District People′s Hospital from January to December 2023 were selected. 73 children with asthma control test score ≥23 were selected as the control group, and 92 children with asthma control test score <23 were selected as the control group. The difference of indexes between the two groups were statistically compared in terms of PFT [forced expiratory volume in one second (FEV 1), ratio of FEV 1 to forced vital capacity (FVC) (FEV 1/FVC), instantaneous forced expiratory flow at 50% of forced vital capacity (FEF 50), instantaneous forced expiratory flow at 75% of forced vital capacity (FEF 75), maximum mid expiratory flow (MMEF), peak expiratory flow (PEF)], and IOS metrics [respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), difference between R5 and R20 (R5-R20), reactance at 5 Hz (X5), total respiratory impedance at 5 Hz (Z5), resonance frequency (Fres), reactance area (AX)]. The predictive value of PFT and IOS indexes to BA was analyzed. Results:The levels of FEV 1, FEV 1/FVC, FEF 50, FEF 75, PEF and MMEF in PFT index of the control group were significantly higher than those in the non-control group, and the levels of Z5, R5, R20, R5-R20, X5, AX and Fres in IOS index were significantly lower than those in the non-control group. There was statistical significance between the two groups (all P<0.05). The area under the curve (AUC) predicted by PFT indexes was less than 0.7, and the AUC of FEF 50 and MMEF (all 0.633) was the largest. Among the IOS indexes, Z5, R5, R5-R20, X5, AX and Fres predicted the AUC of BA uncontrolled to be >0.7, while AX had the largest predictive value for BA uncontrolled (AUC=0.786, 95% CI: 0.736-0.836), sensitivity was 78.26%, specificity was 64.13%. Conclusions:All indexes of PFT and IOS have good sensitivity in evaluating the degree of BA control in children, and IOS has better clinical value in predicting uncontrolled BA, among which AX has the greatest predictive value for uncontrolled BA.