OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

Objective: To explore the setting of gray zone of Treponema pallidum (TP) testing by retrospective analysis of blood donors with single reagent reactive anti-TP results, so as to improve blood utilization and supply safety. Methods: Blood samples were collected from 112 blood donors previously deferred due to single reagent reactive TP antibody results between January 2020 and December 2023, and subjected to dual ELISA reagents and TPPA test. The gray zone panel analysis was performed on the two ELISA reagents currently used in our department. The detection rate at each concentration of the gray zone panle was counted, and the corresponding concentrations for C , C , and C and gray zone cut-off were calculated. Results: Among the 50 samples deferred by reagent 1, 19 were confirmed reactive and 31 non-reactive in supplementary testing. Among the 62 samples deferred by reagent 2, 12 were confirmed reactive and 50 non-reactive in supplementary testing. For reagent 1, the detection rate of was 56% for S/CO≥1 and 20% for 0.5≤S/CO<1, retrospectively. For reagent 2, the detection rate was 27% for S/CO≥1 and 12.5% for 0.5≤S/CO<1, retrospectively. The detection rate for S/CO≥1 was higher than those for 0.5≤S/CO<1 for both reagents. All the 112 samples were negative in TPPA test. The C concentration of reagent 1 was 1.51 mIU/mL, and the concentration range of C ±20% was 1.21-1.81 mIU/mL. The C concentration of reagent 2 was 1.45 mIU/mL, and the concentration range of C ±20% was 1.16-1.74 mIU/mL. The C and C concentration of both reagents were within the C ±20% range, suggesting that the gray zone cutoff for both Reagent 1 and Reagent 2 should be set at S/CO=0.8 (80% of the CO value). Conclusion: All anti-TP single reagent reactive samples with S/CO value within the gray zone was tested negative by TPPA. It is necessary to consider the rationality and necessity of establishing the gray zone, so as to ensure blood safety and improve the utilization rate of blood resources.

Objective:To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT).Methods:Three pregnant women who underwent NIPT testing at Guangdong Women and Children′s from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethic No.: 20230132).Results:Case 1 underwent selective fetal reduction at 8 + weeks of gestation. At 17 + weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks′ gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 ( Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13 + weeks due to fetal abnormalities in one twin. At 22 + weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. Conclusion:In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.

OBJECTIVE: To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT). METHODS: Three pregnant women who underwent NIPT testing at Guangdong Women and Children's from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethics No.: 20230132). RESULTS: Case 1 underwent selective fetal reduction at 8⁺ weeks of gestation. At 17⁺ weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks' gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 (Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13⁺ weeks due to fetal abnormalities in one twin. At 22⁺ weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. CONCLUSION In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.
Adult ; Female ; Humans ; Pregnancy ; Diseases in Twins/diagnosis* ; Karyotyping ; Noninvasive Prenatal Testing/methods* ; Pregnancy, Twin ; Prenatal Diagnosis/methods*

Objective:To assess the impact of vanishing twin syndrome (VTS) on the accuracy of non-invasive prenatal testing (NIPT).Methods:Three pregnant women who underwent NIPT testing at Guangdong Women and Children′s from November 2019 to February 2020 were selected as the study subjects. The three women had either vanish twin syndrome or had undergone fetal reduction for other reasons in one of their twins, and were subsequently subject to NIPT, chromosome karyotyping, chromosome microarray analysis (CMA), and short tandem repeat (STR) analysis. This study has been approved by the Medical Ethics Committee of Guangdong Maternal and Child Health Hospital (Ethic No.: 20230132).Results:Case 1 underwent selective fetal reduction at 8 + weeks of gestation. At 17 + weeks, NIPT showed a fetal DNA fraction of 2.806%, with results indicating the presence of Y chromosome and abnormal sex chromosome ratios. However, the women had subsequent uncomplicated vaginal delivery of a female infant, and no abnormality noted. Case 2 experienced spontaneous demise of one twin at 13 weeks′ gestation. At 19 weeks, NIPT indicated a high risk for chromosome 21 ( Z-score 4.671) in the surviving fetus, but subsequent evaluation showed no abnormality. Case 3, a dichorionic diamniotic (DCDA) twin pregnancy, underwent selective reduction at 13 + weeks due to fetal abnormalities in one twin. At 22 + weeks, NIPT for the surviving fetus indicated a high risk for chromosome 21 (Z-score 17.549), but subsequent evaluation was unremarkable. Conclusion:In twin pregnancies, the relatively low cell-free fetal DNA (cffDNA) concentration can compromise the success rate and accuracy of NIPT compared to singleton pregnancies. Residual DNA from the demised fetus may persist for weeks following VTS or selective reduction, potentially causing false-positive NIPT results and interfering with sex chromosome prediction for the surviving fetus. Additionally, determining chorionicity is critical for reliable interpretation of NIPT results in twin pregnancies.

Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.Methods:Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay. The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Results:Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR. Conclusion:The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum