OBJECTIVE To evaluate the safety of fondaparinux in pregnancy and provide reference for its rational clinical application. METHODS A search was conducted in databases including CNKI， Wanfang， PubMed， Embase， and Elsevier （the search time was from the construction of the database to December 17， 2024） to collect case report literature on fondaparinux use during pregnancy. Patient demographic information， fondaparinux use during pregnancy， concomitant medications， clinical manifestations， and treatment details were extracted for descriptive statistical analysis. RESULTS A total of 17 case reports regarding the use of fondaparinux during pregnancy were collected， involving 42 patients from 11 countries and 47 pregnancy records. Among these， 20 cases involved the use of fondaparinux for the prevention of pregnancy-related venous thromboembolism （VTE）， while 27 cases were fondaparinux treatment due to related conditions. A total of 29 occurrences of the patients were treated with fondaparinux due to a （family） history of VTE. Nine occurrences of complicated pregnancies were reported， and 35 patients had records of comorbidities or relevant medical histories. The adverse events that occurred during pregnancy with the use of fondaparinux include postpartum hemorrhage （7 cases） and excessive anticoagulation caused by inappropriate dosage （1 case）. Among the 7 cases of postpartum hemorrhage， 3 cases had a blood loss of no less than 1 000 mL （including 2 cases with uterine atony）， 3 cases had a drug discontinuation time of ≤12 h. CONCLUSIONS Based on the existing literature， the safety of fondaparinux during pregnancy is generally manageable， with the main adverse event being postpartum hemorrhage. The dosage， interval between discontinuation，comorbidities/medical history， and concomitant medications of fondaparinux may be the main causes of its adverse events.

OBJECTIVE: To investigate the molecular pathogenic mechanisms of a family with hereditary factor Ⅶ (FⅦ) deficiency. METHODS: A family (3 generations, 12 members) with hereditary FⅦ deficiency, in which the proband presented with menorrhagia and was admitted to the First Affiliated Hospital of Wenzhou Medical University in April 2023, was selected as the study subject. Clinical data of the family members were collected. Peripheral venous blood samples were collected from all 12 members for routine coagulation tests and genomic DNA extraction. All exons and flanking sequences of the F7 gene were amplified by PCR and analyzed by Sanger sequencing. Thrombin generation assay was performed to evaluate the coagulation potential of the proband and her parents. Multiple online bioinformatics software tools were used to analyze the conservation and pathogenicity of candidate variants identified in the proband. The pathogenicity of variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). Homology modeling of the variant FⅦ protein was performed using homology modeling (SWISS-MODEL). Amino acid sequence alignment between wild-type and variant FⅦ proteins was conducted using MEGA v7, and spatial conformational differences were analyzed using PyMOL to assess the potential impact of the F7 gene variants on the structure and function of the FⅦ protein. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: Coagulation tests showed that the proband's prothrombin time (PT) was significantly prolonged to 33.1 s, and both factor Ⅶ activity (FⅦ:C) and antigen (FⅦ:Ag) levels were reduced to 2%. Her parents, eldest sister, second sister, younger brother, and four children all showed mildly prolonged PT, with FⅦ:C and FⅦ:Ag levels approximately 50% of normal. Genetic sequencing identified compound heterozygous variants in the F7 gene of the proband: a heterozygous missense variant c.722C>A (p.Thr241Asn) in exon 7, and a heterozygous deletion variant c.1261_1261delA (p.Ile421Ser*fs75) in exon 8. Retrieval from domestic and international databases found no previous reports of the latter variant, suggesting it is novel. Familial co-segregation analysis confirmed that these variants were inherited from her father and mother, respectively. The thrombin generation assay demonstrated that the proband had a significantly decreased peak thrombin height (peak ratio: 29.5%), significantly increased thrombin lag time ratio and time-to-peak ratio (3.03 and 2.93, respectively), but only a mildly decreased endogenous thrombin potential (ETP) ratio of 90.7%. Online bioinformatics analysis indicated that threonine-241 (p.Thr241) in the FⅦ protein was not conserved, while isoleucine-421 (p.Ile421) was highly conserved. Both the p.Thr241Asn and p.Ile421Serfs*75 variant sites in the proband's F7 gene were predicted to be pathogenic. According to the ACMG guidelines, the p.Thr241Asn (PM3+PP1+PP3+PP4+PP5) and p.Ile421Ser*fs75 (PM2+PM4 +PP1+PP3+PP4) variants were both classified as "likely pathogenic". Structural analysis of the FⅦ protein indicated that the p.Ile421Ser*fs75 frameshift variant led to the substitution of Cysteine-428 by Alanine, preventing the formation of a critical disulfide bond between amino acid residues 400 and 428 present in the wild-type FVII protein. CONCLUSION The compound heterozygous variants p.Thr241Asn and p.Ile421Ser*fs75 in the F7 gene are likely the genetic etiology responsible for the reduced FⅦ levels in this hereditary FⅦ deficiency family.
Adult ; Female ; Humans ; Male ; Middle Aged ; China ; Factor VII/chemistry* ; Factor VII Deficiency/genetics* ; Heterozygote ; Mutation ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To investigate the molecular mechanism for a family with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The proband, a 63-year-old female, was admitted to the First Affiliated Hospital of Wenzhou Medical University in August 2024 for lumbar disc herniation. Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), and FⅫ activity (FⅫ:C), were carried out for the proband and her family members (9 individuals from three generations) using a one-stage clotting assay. The level of FⅫ antigen (FⅫ:Ag) was determined with an Enzyme-linked immunosorbent assay (ELISA). Sanger sequencing was conducted to identify potential variants in the F12 gene. Multiple in silico tools were used to predict the conservation, hydrophobicity, and structural impact of the identified variants. Recombinant expression plasmids were constructed and transiently transfected into HEK293T cells. The recombinant FⅫ protein was analyzed using Western blotting (WB) and ELISA. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband showed a markedly prolonged APTT (160.3 s) and significantly decreased FⅫ:C (2%) and FⅫ:Ag (5%) levels. Analysis of the F12 gene sequence revealed a 46C/T genotype in the promoter region, a heterozygous c.1457G>A (p.Cys467Tyr) missense variant in exon 12, and a heterozygous c.1561G>A (p.Glu502Lys) missense variant in exon 13. Bioinformatic analysis showed that the p.Cys467 is highly conserved across various species, and the p.Cys467Tyr variant may affect local structural stability of the FⅫ protein. The p.Cys467Tyr variant had no effect on the transcription of the F12 gene. However, the variant has significantly decreased the FⅫ:Ag levels and FⅫ protein expression in the cell culture supernatant compared to the wild-type expression vector, while in the cell lysate, it is higher than the wild-type expression vector. In other words, the p.Cys467Tyr variant has probably caused a secretion defect of FⅫ protein. CONCLUSION The 46C/T genotype, the heterozygous p.Cys467Tyr missense variant, and the heterozygous p.Glu502Lys missense variant are associated with reduced plasma FⅫ levels in this pedigree. The p.Cys467Tyr variant, which was unreported previously, did not affect the synthesis of FⅫ but may have resulted in a secretion defect.
Humans ; Female ; Middle Aged ; Mutation, Missense ; Pedigree ; HEK293 Cells ; Male ; Factor XII/genetics* ; Adult ; Factor XII Deficiency/genetics*

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

ObjectiveTo investigate the structural and functional characteristics of gut microbiota in common traditional Chinese medicine （TCM） syndromes of irritable bowel syndrome with diarrhea （IBS-D）. MethodsIBS-D patients who visited the Hospital of Chengdu University of Traditional Chinese Medicine， and healthy participants from the Physical Examination Centre of the same hospital were recruited from 1st January 2020 to 31st March 2021.The IBS-D patients were classified into syndrome of liver constraint and spleen deficiency， and syndrome of spleen deficiency and dampness exuberance； together with the recruited healthy participants， there were liver-constraint group， dampness-exuberance group， and healthy group. General information， including age， gender and body mass index （BMI）， were collected， and Irritable Bowel Syndrome Symptom Severity Scale （IBS-SSS） as well as Irritable Bowel Syndrome Quality of Life Scale （IBS-QOL） scores were additionally collected from IBS-D patients. Fresh fecal samples were also collected and tested by macro-genome sequencing technology for abundance statistical display， PCoA， Anosim， LEfSe bioinformatic analysis of the annotated gut microbiota structure and function. ResultsThere was no statistically significant difference in the general information of the participants in the three groups （P＞0.05）； the difference in the IBS-SSS and IBS-QOL scores between liver-constraint group and dampness-exuberance group were not statistically significant （P＞0.05）. The study included 28 cases each in liver-constraint group， dampness-exuberance group， and healthy group. The number of specific genes to patients in liver-constraint group was 269 135， with 216 156 in dampness-exuberance group and 249 759 in healthy group， accounting of total 1 784 036 in the three groups. There were differences in the relative abundance distribution of the top ten species of gut microbiota among the three groups， with smaller differences at the phylum， class and order levels， and larger differences at the family， genus and species levels. There were differences in the relative abundance of structure and function of the gut microbiota among the three groups. Species PCoA and Anosim analyses at the species level showed significant differences in the composition of the microbiota among the three groups. Further LEfSe analyses showed that patients in liver-constraint group were screened for 14 dominant strains， of which Clostridium sp. CAG 217， Lachnospira pectinoschiza， Anaerotruncus sp. CAG 528， Paeniclostridium sordellii， Eubecterium sp. CAG 76， Bacillus cereus were affected to a greater extent in abundance differences； dampness-exuberance group screened 24 species of dominant bacteria， of which Roseburia inulinivorans， Eubacterium sp. CAG 251， Roseburia hominis， Unclassified Eubacterium rectale， Roseburia intestinalis， and Megamonas funiformis were affected to a greater extent in abundance differences； no dominant functional genes were screened for patients in liver-constraint group， and dampness-exuberance group was screened for flagellum assembly （ko02040）， porphyrin metabolism （ ko00860）， salmonella infection （ko05132）， and benzoic acid degradation （ko00362）. The differentially dominant functional genes in liver-constraint group and dampness-exuberance group may mainly focus on metabolism （including biodegradation and metabolism of exogenous substances， energy metabolism， lipid metabolism， etc.）. ConclusionIBS-D with syndrome of liver constraint and spleen deficiency is characterized by the enrichment of 14 gut microbiota， such as Clostridium sp. CAG 217， while IBS-D with syndrome of spleen deficiency and dampness exuberance is characterized by the enrichment of 24 gut microbiota， such as Roseburia inulinivorans， and 4 functional enrichments， such as flagellum assembly. Clostridium sp. CAG 217 and Roseburia inulinivorans are expected to be biomarkers for IBS-D patients in the two syndromes， respectively.

[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent ⁶⁸Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching ⁶⁸Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on ⁶⁸Ga-PSMA-11 PET/CT.

Objective:To explore the psychological experiences of lung cancer patients during treatment based on the perspective of narrative medicine,and to provide references for targeted nursing interventions.Methods:Guided by the concept of narrative medicine,the phenomenological method of qualitative research was used to conduct in-depth interviews with 20 lung cancer patients.The interview data were analyzed,refined,and summarized by using the content analysis method.Results:From the perspective of the humanistic value of narrative medicine,four themes were extracted from the interview contents with 20 lung cancer patients,including the loss of patients'role identity,the experience of disease uncertainty,the fear and expectation of death,and the helplessness and perception of life.Conclusion:During the treatment process of lung cancer patients,there are negative psychological experiences,such as loss of role identity,uncertainty of disease,fear of death,and hope to leave with dignity.Meanwhile,there are positive perceptions,such as contemplation of the meaning of life and actively coping with it.

Anxiety disorders,dopaminergic neurons and ventral tegmental area(VTA)are related closely.VTA dopaminergic neurons play an important role in the regulation of anxiety.Numerous research results in animals indicated that the VTA dopaminergic neurons,involving in multiple neural pathways,respectively regulate anxiety-like behavior in physiological or pathological condition.Dopamine,the main neurotransmitters in VTA regulates anxiety through dopamine D1 and D2 receptors.In addition,the VTA glutamate,GABA and acetylcholine also play directly or indirectly roles in regulating anxiety.The clinical imaging research showed that the integrity of dopaminergic VTA structural of anxiety disorder group is lower than healthy control.Current researches of VTA dopamine neurons involving in the regulation of anxiety-like behavior is developing at a high speed and deserving further exploration,which will further elucidate the pathogenesis and provide new ideas for prevention and treatment of anxiety disorders.

Objective:To investigate the application value of Hisense computer-assisted surgery system (CAS) three-dimensional reconstruction in the precision treatment of pediatric liver tumors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 82 children with liver tumors who were admitted to Affiliated Hospital of Qingdao University from January 2013 to September 2021 were collected. There were 39 males and 43 females, aged 13(19)months. Children underwent upper abdominal dynamic enhanced computed tomography (CT) examination, and three-dimensional reconstruction was performed on CT images of arterial, equili-brium and venous phases with Hisense CAS. Surgical feasibility and scheme were evaluated and conducted based on the results of upper abdominal dynamic enhanced CT examination, and then revised according to three-dimensional reconstruction results of Hisense CAS. Observation indicators: (1) comparison of surgical scheme between two-dimensional enhanced CT images and three-dimensional reconstruction results of Hisense CAS; (2) intraoperative and postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination to detect postoperative compli-cations and residual liver compensation up to November 2021. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were described as absolute numbers or percentages. Results:(1) Comparison of surgical scheme between two-dimensional CT images and three-dimensional reconstruction results of Hisense CAS. ① Based on the two-dimensional CT images, 42 cases of 82 children could undergo one-stage resection and 40 children could not. However, based on the three-dimensional reconstruction results of Hisense CAS, 48 cases of 82 children could undergo one-stage resection and 34 children could not. There were 6 children with one-stage resection feasibility based on the three-dimensional reconstruction results of Hisense CAS rather than the two-dimensional CT images. For the 34 children undergoing chemotherapy firstly, 31 cases had surgical feasibility after chemotherapy based on the two-dimensional CT images and 3 cases could not undergo surgery because of unapparent tumor regression or tumor surrounding impor-tant vessels. However, the 34 children had surgical feasibility after chemotherapy based on the three-dimensional reconstruction results of Hisense CAS. The revision rate of surgical feasibility was 11.0%(9/82) for the 82 children. ② Based on the two-dimensional CT images, 15 cases of 82 children underwent liver left lobectomy, 21 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 13 cases underwent extended left hemihepatectomy, 23 cases underwent extended right hemihepatectomy, 3 cases underwent segmental hepatectomy. However, based on the three-dimensional reconstruction results of Hisense CAS, 20 cases of 82 children underwent liver left lobectomy, 29 cases underwent liver right lobectomy, 7 cases underwent mesohepatectomy, 7 cases underwent extended left hemihepatectomy, 14 cases underwent extended right hemihepatectomy, 5 cases underwent segmental hepatectomy. The revision rate of surgical scheme was 36.6%(30/82) for the 82 children. (2) Intraoperative and postoperative situations. The operation time, volume of intraoperative blood loss, duration of postoperative hospital stay of the 82 children were (182±18)minutes, 20(10)mL, (10.2±1.9)days, respectively. (3) Follow-up. All the 82 children were followed up for 10 (range, 2?18)months. There was no obvious complication occurred to the 82 children after surgery, and the residual liver can satisfy the liver compensation of body. All the children survived well.Conclusion:Three-dimensional reconstruction of Hisense CAS is conducive to judging the surgical feasibility and formulation of accurate surgical plan of children with liver tumors.