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Objective: To evaluate the utility of trio-based prenatal exome sequencing (pES), incorporating splice-site and mitochondrial genome assessment, in the prenatal diagnosis of fetuses with ultrasound anomalies and normal copy-number variant sequencing (CNV-seq) results.Methods: This was a prospective study of 90 ongoing pregnancies with ultrasound anomalies that underwent trio-based pES after receiving normal CNV-seq results, from September 2020 to November 2021, in a single center in China. By using pES with a panel encompassing exome coding and splicing regions as well as mitochondrial genome for fetuses and parents, we identified the underlying genetic causes of fetal anomalies, incidental fetal findings and parental carrier status. Information on pregnancy outcome and the impact of pES findings on parental decision-making was collected.Results: Of the 90 pregnancies included, 28 (31.1%) received a diagnostic result that could explain the fetal ultrasound anomalies. The highest diagnostic yield was noted for brain abnormalities (3/6 (50.0%)), followed by hydrops (4/9 (44.4%)) and skeletal abnormalities (13/34 (38.2%)). Collectively, 34 variants of 20 genes were detected in the 28 diagnosed cases, with 55.9% (19/34) occurring de novo. Variants of uncertain significance (VUS) associated with fetal phenotypes were detected in six (6.7%) fetuses. Interestingly, fetal (n = 4) and parental (n = 3) incidental findings (IFs) were detected in seven (7.8%) cases. These included two fetuses carrying a de-novo likely pathogenic (LP) variant of the CIC and FBXO11 genes, respectively, associated with neurodevelopmental disorders, and one fetus with a LP variant in a mitochondrial gene. The remaining fetus presented with unilateral renal dysplasia and was incidentally found to carry a pathogenic PKD1 gene variant resulting in adult-onset polycystic kidney, which was later confirmed to be inherited from the mother. In addition, parental heterozygous variants associated with autosomal recessive diseases were detected in three families, including one with additional fetal diagnostic findings. Diagnostic results or fetal IFs contributed to parental decision-making about termination of the pregnancy in 26 families (26/72 (36.1%)), while negative pES results or identification of VUS encouraged 40 families (40/72 (55.6%)) to continue their pregnancy, which ended in a live birth in all cases.Conclusion: Trio-based pES can provide additional genetic information for pregnancies with fetal ultrasound anomalies without a CNV-seq diagnosis. The incidental findings and parental carrier status reported by trio-based pES with splice-site and mitochondrial genome analysis extend its clinical application, but careful genetic counseling is warranted. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the bioequivalence of China-manufactured biosimilar, HLX02, to reference China (CN)- and European Union (EU)-sourced trastuzumab.Methods: This was a two-part Phase 1 study conducted in healthy Chinese males. Part 1 evaluated the safety of different doses of HLX02 (2, 4, 6 or 8 mg/kg; intravenous infusion over 90 min, n = 3 per group). Part 2, a randomized, double-blind study, investigated the pharmacokinetics (PK), safety and immunogenicity of study drugs (HLX02 [n = 37], CN-trastuzumab [n = 35] or EU-trastuzumab [n = 37] at the dose suggested by Part 1 results). The primary PK endpoint was the area under the serum concentration-time curve from time 0 to infinity (AUCinf). Equivalence was concluded if the 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) fell in the equivalence criteria of 0.80-1.25.Results: In Part 1, all doses of HLX02 were well tolerated and 6 mg/kg was suggested for Part 2. The GLSMRs and 90% CIs for AUCinf were: 0.950 (0.891-1.013), 0.914 (0.858-0.973) and 0.962 (0.902-1.025) for HLX02 versus CN-trastuzumab, HLX02 versus EU-trastuzumab and CN-trastuzumab versus EU-trastuzumab, respectively. Secondary endpoints comparisons also fell in the equivalence criteria. Treatment-emergent adverse events were reported in 75.7, 86.5 and 70.3% of the subjects in HLX02, CN-trastuzumab, and EU-trastuzumab groups, respectively. No serious adverse events or deaths occurred. No treatment-related anti-drug antibodies were detected.Conclusion: This study demonstrated comparable safety profiles and PK bioequivalence among HLX02, CN-trastuzumab and EU-trastuzumab in healthy Chinese male subjects.Clinical Trial Registration: ClinicalTrials.gov, NCT02581748, registered at October 19, 2015. [ABSTRACT FROM AUTHOR]

Background.Converging evidence has revealed both functional and structural abnormalities in adolescents with early-onset conduct disorder (EO-CD). The neurological abnormalities underlying EO-CD may be different from that of adolescent-onset conduct disorder (AO-CD) patients. However, the cortical structure in AO-CD patients remains largely unknown. The aim of the present study was to investigate the cortical alterations in AO-CD patients.Method.We investigated T1-weighted brain images from AO-CD patients and age-, gender- and intelligence quotient-matched controls. Cortical structures including thickness, folding and surface area were measured using the surface-based morphometric method. Furthermore, we assessed impulsivity and antisocial symptoms using the Barratt Impulsiveness Scale (BIS) and the Antisocial Process Screening Device (APSD).Results.Compared with the controls, we found significant cortical thinning in the paralimbic system in AO-CD patients. For the first time, we observed cortical thinning in the precuneus/posterior cingulate cortex (PCC) in AO-CD patients which has not been reported in EO-CD patients. Prominent folding abnormalities were found in the paralimbic structures and frontal cortex while diminished surface areas were shown in the precentral and inferior temporal cortex. Furthermore, cortical thickness of the paralimbic structures was found to be negatively correlated with impulsivity and antisocial behaviors measured by the BIS and APSD, respectively.Conclusions.The present study indicates that AO-CD is characterized by cortical structural abnormalities in the paralimbic system, and, in particular, we highlight the potential role of deficient structures including the precuneus and PCC in the etiology of AO-CD. [ABSTRACT FROM PUBLISHER]

BackgroundThe self-referential memory (SRM) effect refers to the phenomenon that stimuli processed with reference to the self are better remembered than those referenced to others. Studies have shown that schizophrenia patients do not have this memorial advantage for self-referenced information. The current study investigated the electrophysiological mechanism of the abolished SRM effect in schizophrenia.MethodTwenty schizophrenia patients and 22 controls were recruited to complete an SRM task. We used a high-time resolution event-related potential (ERP) technique to analyze the electrophysiological differences between patients and controls during self- and other-reflection processing.ResultsBehavior data indicated that healthy controls had a typical SRM bias that was absent in the schizophrenia patients. ERP comparison between groups showed that the schizophrenia patients presented smaller voltages in both self- and other-reflection conditions in the 160–260 ms (P2 component) and 800–1200 ms (positive slow wave) time windows over the pre/frontal cortex. Furthermore, the N2 amplitudes (270–380 ms) differed between self- and other-reflection conditions in patients but not in normal controls. More importantly, we found that the P3 amplitudes in the parietal cortex correlated significantly with the SRM bias score in the patients (r = –0.688).ConclusionsThese results provide comprehensive and direct electrophysiological evidence for self- and other-reflective dysfunction in schizophrenia patients and contribute to our understanding of the underlying neural substrates of the abolished SRM effect in schizophrenia. [ABSTRACT FROM AUTHOR]

The article focuses on demonstrating a simple and safe cardiopulmonary bypass (CPB) model without blood priming in rats. It presents the conditions that should be contained in the model which include precise control of temperature and depth of anesthesia, good stability and repeatability, and similarity to clinical cardiac surgery. Other requirements include long-term survival and preparation for the further research into deep hypothermic circulatory arrest (DHCA).

Zhu XL, Meng HX, Zhang L, Xu L, Chen ZB, Shi D, Feng XH, Zhang X. Association analysis between the −2518MCP-1(A/G) polymorphism and generalized aggressive periodontitis in a Chinese population. J Periodont Res 2012; 47: 286-292. © 2011 John Wiley & Sons A/S Background and Objective: It has been suggested that aggressive periodontitis has a genetic basis. Monocyte chemoattractant protein 1 (MCP-1) plays a critical role in the recruitment of monocytes and the development of periodontitis. The −2518MCP-1(A/G) polymorphism has been implicated as a risk or susceptibility factor for a variety of autoimmune conditions and inflammatory diseases. The intent of this investigation was to study whether the −2518MCP-1(A/G) polymorphism is associated with generalized aggressive periodontitis in the Chinese population. Material and Methods: One hundred and twenty-four patients with generalized aggressive periodontitis and 94 healthy subjects were included in this case-control study. Genomic DNA was isolated from a peripheral blood sample obtained from each subject. Gene polymorphisms of −2518MCP-1(A/G) were analyzed by a standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A logistic regression analysis was performed to test the association between the −2518MCP-1(A/G) genotype (alleles) and generalized aggressive periodontitis with adjustment of the major covariates (gender, age and smoking status). Results: There was no significant association of the −2518MCP-1(A/G) polymorphism with generalized aggressive periodontitis in the unstratified subjects. However, when patients were stratified by gender, the frequency of the G+ genotype was significantly lower in female patients with generalized aggressive periodontitis compared with female controls ( p = 0.036, adjusted odds ratio = 0.3, 95% CI: 0.1-0.9). In female patients with generalized aggressive periodontitis, the probing pocket depth was larger in subjects with the AA genotype than in subjects with the G+ genotype (5.07 mm vs. 4.30 mm; Z = −2.470, p = 0.014). Conclusion: The polymorphisms of −2518MCP-1 may play an important role in determining generalized aggressive periodontitis susceptibility in this cohort of Chinese women. [ABSTRACT FROM AUTHOR]

BackgroundIn Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China?MethodReceived parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview.ResultsFactor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD.ConclusionsAlthough the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. [ABSTRACT FROM PUBLISHER]