Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of PubMed database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis, involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations (P= 0.028, OR= 1.138, 95% CI: 1.014–1.278; P = 0.004 for heterogeneity) and Asian populations (P = 0.008, OR = 1.092, 95% CI: 1.023–1.165; P = 0.001 for heterogeneity), but not in other populations (P= 0.286, OR= 1.209, 95% CI: 0.853–1.714, P = 0.120 for heterogeneity). Egger’s test (P > 0.05) and Begg’s test (P>0.05) are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.

Objective To further improve the value of clinical application of a quantitative analysis method called LF-index (LFI) which based on real-time tissue elastography (RTE). Methods We prospectively enrolled 116 consecutive patients with chronic hepatitis B (CHB) and all patients underwent a liver biopsy and RTE between January 2015 and December 2015 at the First affiliated hospital of Wenzhou Medical University. Univariate and multivariate analyses were performed, and the prediction models for predicting significant fibrosis and cirrhosis were derived from independent predictors. Results (1) In multivariate analyses, spleno-portal index (SPI) (OR=13.956, P=0.002) and LFI (OR=6.283, P=0.023) were confirmed as independent predictors of significant fibrosis. In multivariate analyses of patients with and without cirrhosis, we found significant differences in the γ-Glutamyl transferase (GGT) (OR=1.012, P=0.049), SPI (OR=5.676, P=0.002) and LFI (OR=14.102, P=0.001). (2)A novel model called LFI-SPI score (LSPS) for prediction of significant fibrosis was developed (area under receiver operating characteristic curve [AUROC]=0.87), showing the superiority of diagnostic accuracy than LFI (AUROC=0.76, P=0.0109), aspartate aminotransferase to platelet ratio index (APRI) (AUROC=0.64, P=0.0031), fibrosis-4 index (FIB-4) (AUROC=0.67, P= 0.0044) and Fibroscan (AUROC=0.68, P=0.0021). (3) We also developed a LFI-SPI-GGT score (LSPGS) for predicting cirrhosis, with an AUROC of 0.93. The diagnostic accuracy of LSPGS was similar to that of Fibroscan (AUROC=0.85, P=0.134), and was superior to LFI (AUROC=0.81, P=0.0113), APRI (AUROC=0.67, P<0.0001), and FIB-4 (AUROC=0.72, P=0.0005). Conclusions We developed new formulas, LSPS and LSPGS for predicting significant fibrosis and cirrhosis in this prospective study. LSP score was mainly used for screening of significant liver fibrosis, and LSPG score was mainly used to exclude cirrhosis.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Alzheimer′s disease is a progressive neurodegenerative disease that requires medication to improve patient symptoms, but there is an individual difference in the efficacy. In this paper, the correlation between single nucleotide polymorphism and the drug efficacy of Alzheimer′s disease (AD) in the past 20 years was searched through the databases of China National Knowledge Infrastructure, VIP Database, Wanfang Database, Pubmed, Springer Link and Cochrane Library with key words of Alzheimer′s disease, drug efficacy, single nucleotide polymorphism. The correlation between AD drug efficacy difference and gene single nucleotide polymorphism was reviewed, including ABCA1, ApoE, ChAT, CHRNA7, IL-6, A2M, CYP2D6, BChE, 5HT2a, PON-1 and ESR1 genes, so as to provide a reference basis for clinicians to select drugs in the treatment of AD.

Objective:To investigate the power and prenatal diagnosis strategies of cell-free fetal DNA (cffDNA) testing for chromosomal aneuploidy screening apart from trisomy-13/18/21.Methods:This study collected the clinical data of three cases at high risk of trisomy-16 indicated by cffDNA testing in Hunan Provincial Maternal and Child Health Care Hospital from March 2019 to March 2020. Results of the conventional G-banding karyotype analysis of amniotic fluid, single nucleotide polymorphism array (SNP-array) and low-coverage massively parallel copy number variation sequencing (CNV-seq) of placenta/fetal skin samples were analyzed.Results:(1) cffDNA testing results suggested that case 1-3 were at high risk of trisomy-16 and the Z values of chromosome 16 were 20.57, 24.88 and 17.87, respectively. (2) Karyotype analysis of amniotic fluid samples did not identify any abnormalities in Case 1 and 2, while SNP-array revealed a 19.2 Mb and 23.0 Mb heterozygous deletion at 16p13.3p12.3 and 16q22.1q24.3 in Case 1, and a 16.0 Mb loss of heterozygosity at 16q22.3q24.3 in Case 2. Case 3 had a mosaicism karyotype of 47,XY,+16[3]/46,XY[97] and SNP-array analysis showed no heterozygous deletion greater than 5 Mb or copy number variation. (3) Ultrasonography indicated fetal growth restriction in Case 1 and 2 and fetal death in Case 3. All three pregnancies were terminated. CNV-seq analysis of placental tissue in the center of both fetal and maternal side revealed mosaic trisomy 16, with the copy numbers of chromosome 16 of 2.56/2.70, 2.73/2.82, 2.80/2.81, respectively. However, no copy number variation was detected in Case 1 or 2 by CNV-seq analysis of fetal skin tissues. Conclusions:cffDNA testing has a certain power in detecting trisomy-16 apart from trisomy-13/18/21. For high-risk cases of trisomy-16 indicated by cffDNA testing, SNP-array analysis combined with karyotype analysis is suggested to rule out low-level mosaicism and loss of heterozygosity.

Objective:Comparison of four methods in intraoperative abduction angles (AA) measurements of human cast immobilization in developmental dysplasia of the hip (DDH) by visual inspection and electronic software according to different body surface markers.Methods:Data were retrospectively collected from January 2019 to November 2021 in a total of 27 patients (54 hips) who underwent closed or simple open reduction. There were 6 males and 21 females with an average age of 13.2 months. Five doctors used visual inspection and mobile phone software to measure the AA of the hip joint immediately during the operation, and compared with the postoperative MRI measurement results (AA-MRI). The four methods of intraoperative measurement were: Junior visualization (AA-JV), the intersection angle between the line connecting the center of the popliteal fossa and the contact center of the plaster frame and the line connecting the two ischial tuberosities; the same methods as method one by Senior visualization (AA-SV); the intersection angle between the line connecting the center of the popliteal fossa and the center of the anus and the line connecting the ischial tubercle (anus-popliteal, AA-AP); the intersection of the vertical line between the center of the popliteal fossa and the groin and the horizontal line of the center of the anus and the vertical line connecting the two ischial tuberosities intersect (anus-groin crease-popliteal, AA-AGCP). The t-test, correlation coefficient, linear regression and Bland-Altman test were used to evaluate the measurements. Results:Comparing the four intraoperative and postoperative AA-MRI measurement methods, AA-JV (42.69°±4.13°) < AA-SV (44.80°±4.08°) < AA-AGCP (46.25°±5.15°) < AA-MRI (47.68°±4.21°) < AA-AP (51.77°±5.30°), and the difference between AA-JV and AA-SV, AA-AP and AA-AGCP was statistically significant ( t=2.53, P=0.013; t=5.47, P=0.001), there was no significant difference between AA-AGCP and AA-MRI ( t=1.57, P=0.118). The inter-group agreement of the five methods ICC test ranged from 0.807 to 0.892, and the intra-group average agreement of AA-MRI was 0.948. All ICC results were greater than 0.75 with good agreement. Linear regression results showed that the four intraoperative measurement methods had a good or moderate linear relationship with AA-MRI, AA-AGCP ( R 2=0.499)>AA-AP ( R 2=0.318)>AA-SV ( R 2=0.253)>AA-JV ( R 2=0.217), AA-AGCP was the best measurement method. The results of Bland-Altman scatterplot of AA-AGCP and AA-MRI were in good agreement, the mean and standard deviation of bias were -0.796±3.247, and the limit of agreement was 95% LoA (-7.16, -5.57). Conclusion:The AA method of visualization before Spica casting was smaller than truth. The method AA-AGCP objectively by landmarks was the advocated means measuring abduction angle during operation with highly consistency, agreement and easily performed.

Objective:To construct an anticipatory grief intervention scheme for family caregivers of advanced cancer patients based on narrative theory, and to provide reference for anticipatory grief nursing intervention.Methods:From October 2022 to May 2023, through literature research, semi-structured interview and brainstorming method, the first draft of nursing intervention plan was constructed, the Delphi method was used to conduct 2 rounds of correspondence consultation with 15 experts, and the indicators at all levels were modified according to the opinions of experts, and the final draft of intervention plan was formed.Results:The experts were all female, aged (49.67 ± 5.83) years old. The authority coefficient of the two rounds of experts was 0.87. The Kendall coordination coefficients of the first, second, and third level indicators after the first round of expert inquiry were 0.195, 0.113, and 0.093, respectively. The Kendall coordination coefficients of the first, second, and third level indicators after the second round of expert inquiry were 0.200, 0.119, and 0.101, respectively. The differences were statistically significant ( χ2 values were 8.76-107.21, all P<0.05).Finally, a nursing intervention plan based on narrative theory was formed, which included 4 primary indicators, 19 secondary indicators and 72 tertiary indicators. Conclusions:The anticipatory grief intervention scheme for family caregivers of advanced cancer patients is scientific, practical and feasible, and can be used for psychological nursing of family caregivers.

In order to develop clinical diagnostic tools for rapid detection of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) and to identify candidate proteins for vaccine development, the C-terminal portion of the nucleocapsid (NC) gene was amplified using RT-PCR from the SARS-CoV genome, cloned into a yeast expression vector (pEGH), and expressed as a glutathione S-transferase (GST) and Hisx6 double-tagged fusion protein under the control of an inducible promoter. Western analysis on the purified protein confirmed the expression and purification of the NC fusion proteins from yeast. To determine its antigenicity, the fusion protein was challenged with serum samples from SARS patients and normal controls. The NC fusion protein demonstrated high antigenicity with high specificity, and therefore, it should have great potential in designing clinical diagnostic tools and provide useful information for vaccine development.
Antigens, Viral ; immunology ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; Genetic Vectors ; Genome, Viral ; Humans ; Nucleocapsid Proteins ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; isolation & purification ; metabolism ; SARS Virus ; genetics ; immunology ; Yeasts ; genetics

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

Objective:To analyze fetal sex chromosome abnormalities in prenatal diagnosis based on amniotic fluid cell culture.Methods:Clinical data of 12 164 pregnant women who underwent amniocentesis in Maternal and Child Health Hospital of Hunan Province from January 2017 to December 2020 were retrospectively analyzed. For those diagnosed with fetal sex chromosome abnormalities, the results of karyotyping and chromosome microarray analysis (CMA) were analyzed and described.Results:(1) Among the 12 164 cases, fetal sex chromosome abnormalities were detected in 387 cases (3.2%), including 351 cases with abnormal sex chromosome karyotype and 36 with sex chromosome microdeletion/microduplication. (2) High-risk patients indicated by non-invasive prenatal test (NIPT) had the highest proportion of sex chromosomes abnormalities (74.2%, 287/387), followed by those with other ultrasound abnormalities (8.5%, 33/387), high risk of Down syndrome screening (7.0%, 27/387), advanced maternal age (4.7%, 18/387), history of adverse pregnant or delivery (3.3%, 13/387), and nuchal translucency thickening or cervical lymphatic hygroma (2.3%, 9/387). (3) Detected chromosome karyotype abnormalities included numerical abnormalities [73.2%(257/351)], mosaicism [18.8(66/351)], and structural abnormalities [8.0%(28/351)], among which, 47,XXY [46.7%(120/257)], 45,X/46,XX[48.5%(32/66)], and X chromosome deletion [39.3%(11/28)] were the most common, respectively. Among 36 sex chromosome microdeletions/microduplications cases, 15(41.7%) were with pathogenic copy number variation (CNV), including 14 cases of X chromosome microdeletion/microduplication; 7(19.4%) with benign CNV, and 14(38.9%) with CNV of unknown clinical significance. The fragment size [ M (min-max)] of the 15 pathogenic CNV was 1.68 Mb(0.37-9.20 Mb). Of the nine cases with microdeletions, seven were found with deletion in the Xp22.31 region. Conclusions:Numerical abnormalities are the most common fetal sex chromosome abnormalities detected from amniotic fluid samples. Others included mosaicism and chromosome structure abnormalities.