OBJECTIVE: To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree. METHODS: A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034). RESULTS: Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. WES identified compound heterozygous variants in BUB1B, i.e., c.2363_2364del (p.S788Cfs*29) and ss804270619: G>A, in both fetuses. Sanger sequencing confirmed paternal inheritance of c.2363_2364del and maternal inheritance of ss804270619:G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c.2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. CONCLUSION The compound heterozygous variants c.2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.
Humans ; Female ; Pregnancy ; Adult ; Mosaicism ; Protein Serine-Threonine Kinases/genetics* ; Chromosome Disorders/diagnosis* ; Pedigree ; Heterozygote ; Prenatal Diagnosis ; Aneuploidy ; Male ; Fetus ; Karyotyping

Objective:To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree.Methods:A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034).Results:① Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. ② WES identified compound heterozygous variants in BUB1B — c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A — in both fetuses. Sanger sequencing confirmed paternal inheritance of c. 2363_2364del and maternal inheritance of ss804270619: G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource(ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c. 2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. Conclusion:The compound heterozygous variants c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.

Objective:To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree.Methods:A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034).Results:① Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. ② WES identified compound heterozygous variants in BUB1B — c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A — in both fetuses. Sanger sequencing confirmed paternal inheritance of c. 2363_2364del and maternal inheritance of ss804270619: G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource(ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c. 2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. Conclusion:The compound heterozygous variants c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To investigate the association of exposure to PM 2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods:We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM 2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM 2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results:A 10 μg/m 3 increase in PM 2.5 exposure during pregnancy was associated with a decrease of 0.025 ( β=-0.025, 95% CI: -0.048- -0.001) in HC Z-score, 0.026 ( β=-0.026, 95% CI: -0.049- -0.003) in AC Z-score, and 0.028 ( β=-0.028, 95% CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% ( RR=1.085, 95% CI: 1.010-1.165) and 13.5% ( RR=1.135, 95% CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM 2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO 42-) and ammonium consistently correlated with decreased HC Z-score. SO 42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions:Our findings demonstrated that exposure to PM 2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

Objective:To explore the intervention effect of sensorimotor training on cognitive function, balance and fall risk of elderly patients with schizophrenia.Methods:The 60 hospitalized elderly schizophrenic patients in Wuxi Mental Health Center were randomly divided into experimental group and control group from June to September 2021, with 30 cases in each group. The control group implemented traditional exercise on the basis of routine nursing. The experimental group received 8-week and 24 times sensorimotor training on the basis of the routine nursing. The Chinese version of the Mini Mental State Examination (MMSE) was used to assess the cognitive level of patients, the Modified Morse Fall Scale (MMFS) was used to assess the risk of falls, and the Berg Balance Scale (BBS) was used to assess the balance function.Results:After 8 weeks of intervention, the total score of MMSE was (26.72 ± 1.71), higher than the total score of the control group (22.36 ± 1.93), the factor scores of temporal orientation, spatial orientation, recollection, attention and calculation, memory and language ability in the experimental group were (4.90 ± 0.31), (4.72 ± 0.53), (2.86 ± 0.35), (4.66 ± 0.61), (2.83 ± 0.47), (6.76 ± 1.09), higher than scores of the control group (4.36 ± 0.56), (3.93 ± 0.66), (2.57 ± 0.50), (3.64 ± 1.03), (2.18 ± 0.67), (5.68 ± 1.02), and the difference was statistically significant( t values were 2.53-9.06, all P< 0.05). The total score of MMFS in the experimental group was (5.93 ± 1.49), which was lower than that in the control group (8.75 ± 2.30). The difference was statistically significant ( t=-5.51, P<0.01). The total score of BBS in the experimental group was (38.83 ± 1.71), which was higher than that in the control group (30.89 ± 1.93). The difference was statistically significant ( t=16.43, P<0.01). Conclusions:Sensorimotor training can improve the level of balance, cognitive function and reduce the risk of falls in elderly patients with schizophrenia.

Objective:To explore the feasibility, safety and effectivity of applying transmesenteric vein extrahepatic portosystemic shunt (TEPS) to treat extrahepatic portal vein obstructive disease (EHPVOD).Methods:From December 2020 to April 2021, 12 patients with EHPVOD in the Vascular Surgery Department of Zhengzhou University People′s Hospital were prospectively enrolled in the study. The infra-umbilical median longitudinal minilaparotomy was performed to expose the branch of superior mesenteric vein (SMV). RUPS-100 was introduced into the trunk of SMV. A balloon with a diameter of 20 mm was introduced through right internal jugular vein (RIJV) into inferior vena cava (IVC). Under fluoroscopy, RUPS-100 was used to puncture the balloon in IVC. A stiff guide wire was used to establish the pathway between RIJV and SMV. Finally the portosystemic shunt between IVC and SMV was established with a covered stent-graft. The total operative time, the time of establishing portosystemic shunt alone, the dosage of contrast agent, the preoperative and postoperative pressure of SMV were recorded. Paired t test was used to compare the preoperative and postoperative pressure of SMV. Results:All 12 patients were successfully performed TEPS. The total operative time was (113±32) min, the time of establishing portosystemic shunt alone was (31±5) min, the dosage of contrast agent was (129±48) ml. The postoperative pressure of SMV [(14.3±2.1) mmHg] decreased significantly ( t=20.125, P<0.01) compared to baseline [(27.8±2.7) mmHg]. All portal hypertension symptoms released after the operations.There was 1 case of delayed incision healing, 1 case of bacteremia and 1 case of slight hepatic encephalopathy, but all of them were cured. There was no death case. Postoperative CT showed all portosystemic shunts were patent. Conclusion:TEPS is a new, safe, effective and feasible treatment method for patients of acute and chronic EHPVOD.

Birth cohort is an important observational study which can continuously and dynamically collect the exposure changes and health outcomes from gametophyte development to adolescence and even old age. However, because of its complex design and difficult implementation, how to construct birth cohort with high quality and high efficiency is the main difficulty faced by epidemiologists at home and abroad. In 2016, China National Birth Cohort was officially launched. The network and information technology were used to explore, and a set of "cloud-based information platform" was established to support this queue construction, containing 16 units in China. After four years of development, the platform has formed a complete set of programs about the construction of cohort information platform, which including recruitment and follow-up management of participants, real-time data interaction, queue quality control, multi-level authority management and function division. The relevant design framework and functional elements provide the references to the future information construction of large-scale birth cohort and even population-based research in China.

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.

Surgical minimally invasive techniques such as image intervention, laparoscopy, endoscopy, and assisted medical robotics have become the mainstream of minimally invasive surgery (MIS). However, the vague concept, diverse misunderstanding, and the lack of standards have led to a lot of malpractice in current MIS. Based on the analysis of the clinical situation and the domestic and foreign literatures, the authors have put forward the theory of comprehensive minimally invasive surgery (CMIS), and established the concepts of minimally invasive prevention, minimally invasive diagnosis and minimally invasive follow-up in the view of hepatobiliary surgery. The authors have proposed "three-All" principles of all personnel, all aspects and all processes, and established a comprehensive four-level criteria of outcomes, complications, time and costs for CMIS, in an attempt to provide feasible and practical concepts and standards for MIS from a clinical practice and theoretical level, with a view to standardizing minimally invasive procedures and solving the problem of MIS.