Objective:To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs).Methods:A total of 28 unrelated CFDs patients admitted to Wenzhou People′s Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg: C), fibrinogen antigen (Fg: Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted by PolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People′s Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment.Results:The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. ①Clinical data: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg: C. ②Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c. 902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c. 569 A>G (28.6%, 8/28). ③Biological informatics analysis: the Aα c. 180+ 1G>T mutation was predicted to be highly deleterious. And the Aα c. 104G>A, Bβ c. 425T>G, Bβ c. 586C>T, and γ c. 902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ④ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c. 104G>A, Aα c. 180+ 1G>T, Bβ c. 425T>G, Bβ c.569A>G, Bβ c. 586C>T, Bβ c. 643G>A, γ c. 901C>T, γ c. 902G>A, γ c. 1001A>C) were classified as pathogenic, while one variation (γ c. 908C>G) was classified as likely pathogenic. Conclusion:In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.

OBJECTIVE: To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs). METHODS: A total of 28 unrelated CFDs patients admitted to Wenzhou People's Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg:C), fibrinogen antigen (Fg:Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted byPolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People's Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment. RESULTS: The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. CLINICAL DATA: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg:C. Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c.902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c.569 A>G (28.6%, 8/28). Biological informatics analysis: the Aα c.180+1G>T mutation was predicted to be highly deleterious. And the Aα c.104G>A, Bβ c.425T>G, Bβ c.586C>T, and γ c.902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c.104G>A, Aα c.180+1G>T, Bβ c.425T>G, Bβ c.569A>G, Bβ c.586C>T, Bβ c.643G>A, γ c.901C>T, γ c.902G>A, γ c.1001A>C) were classified as pathogenic, while one variation (γ c.908C>G) was classified as likely pathogenic. CONCLUSION In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.
Humans ; Female ; Male ; Afibrinogenemia/congenital* ; Fibrinogen/metabolism* ; Mutation ; Genotype ; Adult ; Child ; Adolescent ; Child, Preschool ; Infant

Objective:To explore the clinical features and genetic mutation sites of 28 patients with Congenital fibrinogen disorders (CFDs).Methods:A total of 28 unrelated CFDs patients admitted to Wenzhou People′s Hospital from June 2018 to April 2023 were enrolled into this research. A total of 2.7 mL of peripheral blood was collected from each patient for coagulation function tests, which included thrombin time (TT), fibrinogen activity (Fg: C), fibrinogen antigen (Fg: Ag), and gene detection. The Sanger sequencing method was employed to verify variations in the fibrinogen (Fg) protein-coding gene across 28 patients. Bioinformatics analyses, including harmfulness analysis, conservation analysis across different species, and spatial simulation predictions of variant proteins, were conducted by PolyPhen-2, PROVEAN, SnapGene, and Pymol softwares on the variant sites of these patients. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study received approval from the Ethics Committee of Wenzhou People′s Hospital (Approval No. KY-2023-269), and informed consent was obtained from all participants before enrollment.Results:The clinical and genetic characteristics of 28 patients with CFDs in this study were as follows. ①Clinical data: Among the 28 patients, 2 cases were diagnosed with type I CFDs, while 26 cases were diagnosed with type II CFDs. And 50.0% (14/28) of the patients exhibited no clinical manifestations, while 28.6% (8/28) presented with bleeding manifestations, and 7.1% (2/28) exhibited thrombus manifestations, 3.6% (1/28) experienced both bleeding and thrombosis. Among female patients, 13.0% (3/23) exhibited a history of habitual abortion. All patients demonstrated TT and a significant decrease in Fg: C. ②Sanger sequencing revealed a total of 10 types of heterozygous variations in the FGA, FGB, and FGG genes across 28 patients, distributed among 9 loci. The variation at the γ c. 902G>A/c.901C>T accounted for the highest proportion (35.7%, 10/28), followed by the Bβ c. 569 A>G (28.6%, 8/28). ③Biological informatics analysis: the Aα c. 180+ 1G>T mutation was predicted to be highly deleterious. And the Aα c. 104G>A, Bβ c. 425T>G, Bβ c. 586C>T, and γ c. 902G>A/c.901C>T variations were also predicted to be harmful. Conservation analysis indicates that the 9 variant sites were highly conserved among homo sapiens, musculus, ovis aries, scrofa, and rattus. Spatial conformation analysis revealed that some variations lead to an increase or decrease in the number of hydrogen bonds. ④ACMG guideline rating analysis: Among the ten variations in the Fg protein-coding genes FGA, FGB, and FGG identified in 28 patients, 9 variations (Aα c. 104G>A, Aα c. 180+ 1G>T, Bβ c. 425T>G, Bβ c.569A>G, Bβ c. 586C>T, Bβ c. 643G>A, γ c. 901C>T, γ c. 902G>A, γ c. 1001A>C) were classified as pathogenic, while one variation (γ c. 908C>G) was classified as likely pathogenic. Conclusion:In this study, the majority of CFDs patients are diagnosed with type II CFDs, with 50% presenting clinical symptoms predominantly manifesting as bleeding, thrombosis, and recurrent miscarriage. The mutation hotspots are mainly located in exon 2 of FGA, exon 4 of FGB, and exon 8 of FGG.

The role of glial scar after intracerebral hemorrhage(ICH)remains unclear.This study aimed to inves-tigate whether microglia-astrocyte interaction affects glial scar formation and explore the specific function of glial scar.We used a pharmacologic approach to induce microglial depletion during different ICH stages and examine how ablating microglia affects astrocytic scar formation.Spatial transcriptomics(ST)analysis was performed to explore the potential ligand-receptor pair in the modulation of microglia-astrocyte interaction and to verify the functional changes of astrocytic scars at different periods.During the early stage,sustained microglial depletion induced disorganized astrocytic scar,enhanced neutrophil infiltration,and impaired tissue repair.ST analysis indicated that microglia-derived insulin like growth factor 1(IGF1)modulated astrocytic scar formation via mechanistic target of rapamycin(mTOR)signaling activation.Moreover,repopulating microglia(RM)more strongly activated mTOR signaling,facilitating a more protective scar formation.The combination of IGF1 and osteopontin(OPN)was necessary and sufficient for RM function,rather than IGF1 or OPN alone.At the chronic stage of ICH,the overall net effect of astrocytic scar changed from protective to destructive and delayed microglial depletion could partly reverse this.The vital insight gleaned from our data is that sustained microglial depletion may not be a reasonable treatment strategy for early-stage ICH.Inversely,early-stage IGF1/OPN treatment combined with late-stage PLX3397 treatment is a promising therapeutic strategy.This prompts us to consider the complex temporal dynamics and overall net effect of microglia and astrocytes,and develop elaborate treatment strategies at precise time points after ICH.

Objective:To describe the incidence, diagnosis rate, treatment rate and treatment pattern of hyperkalemia, and serum potassium retesting rate among hyperkalemia patients in the emergency department.Methods:Data were derived from Military Data Center for Rational Use of Drugs. Patients who accessed emergency medical services (≥18 years old) with record(s) of serum potassium between 2015 and 2017 were included. The data of laboratory test, diagnosis, and treatment were analyzed. The main outcomes included the incidence of hyperkalemia, the diagnosis rate, the treatment rate, treatment pattern and the 7-day retesting rate.Results:A total of 1 039 245 patients who met the above criteria were included, of whom, 36 615 (3.52%) had at least one hyperkalemia event. Among the emergency patients with chronic kidney disease, heart failure, diabetes mellitus and hypertension, the proportions of patients who experienced hyperkalemia were 47.69%, 29.13%, 21.69% and 10.16%, respectively. The diagnosis rate of emergency hyperkalemia patients was 9.23%. The overall hyperkalemia treatment rate was 42.1%. Insulin + glucose injection was the most commonly used therapy for emergency hyperkalemia patients. The overall serum potassium retesting rate within 7 days was 28.8%.Conclusions:Hyperkaliemia is more common and more severe in patients with chronic kidney disease, heart failure, diabetes and hypertension. The diagnosis rate and retesting rate of hyperkalemia are low, suggesting that the identification and management of hyperkaliemia in emergency patients should be strengthened.

Objective To explore the associations of anxiety with optimism ,resilience and related demographic factors in lung cancer patients , and to provide a scientific basis for reducing the level of anxiety and improving the psychosomatic health. Methods A total of 130 lung cancer pa-tients from the department internal medicine of respiratory tumors in Liaoning Cancer Hospital&Institute were investigated by convenience sam-pling method from February 2013 to January 2014. The survey was anonymous. Finally,107 questionnaires were effective,and the effective rate was 82.307%. Results Among lung cancer patients,optimism and resilience were positively and significantly associated with anxiety. Physical ex-ercise had an effect on the anxiety symptoms. Conclusion Optimism and resilience have significant predictive value on the anxiety among lung cancer patients. It is important to encourage lung cancer patients to improve their psychological health ,so as to reduce their anxiety symptoms effec-tively.

Objective To track the migration and incorporation of intravenously injected, magneti?cally labeled endothelial progenitor cells ( EPCs) from mouse bone marrow into the blood vessels in a rapid?ly growing HCC model by microMR (7.0 T). Methods This study was approved by the Institutional Com?mittee on Animal Research. H22 hepatic ascitic cancer cells was directly injected into the left liver lobe of BALB/c nude mice ( n=15) . EPCs derived from bone marrow of C57BL/6 mice were isolated and cultured. The third passage EPCs were collected and labeled with 25 μg/ml superparamagnetic iron oxide ( SPIO) and poly?l?lysine (PLL) complex (SPIO?PLL). MTT assay and flow cytometry were used to evaluate the difference of growth curve and apoptosis between labeled and unlabeled EPCs. EPCs labeled with SPIO?PLL were injected into mice via tail vein in experiment group (on the 3rd day after establishing HCC model) (n=15) and control group (n=6). The signal changes of tumor (the 1st, 3rd and 7th day after transplantation) were observed by microMR. Prussian blue staining and immunohistochemistry staining of CD31 were per?formed. MRI findings were confirmed by histomorphology. Two?sample t test was used to analyze the data. Results Single tumor was showed in the liver of all mice 3 d after establishing models. Labeling with SPIO?PLL at a concentration of 25μg/ml did not alter cell growth curve ( measured by MTT assay;t=0.281, P>0.05) and cell apoptosis (analyzed by flow cytometry). The apoptosis rates of SPIO?PLL labeled and un?labled EPCs were (12.31±1.43)% and (11.57±1.24)% in early stage, and (0.55±0.07)% and (0.49± 0?05)% in late stage. No significant differences were observed between them (t=0.967, 1.060; both P>0?05) . Migration and incorporation of transplanted and labeled cells into tumor were documented with in vivo microMR as low signal intensity at the tumor periphery as early as the 3rd day after EPCs administration in preformed tumors (4/5). Prussian blue staining showed iron?positive cells at the sites corresponding to low signal intensity on MRI. The positive cells expressing CD31 existed in intratumoral and peritumoral vessels. There was no signal change in control group at all time points. Conclusions MRI can demonstrate the in?corporation of magnetic labeled mouse EPCs into the implanted hepatoma. It may be helpful for early diagno?sis and therapy of liver tumor.

Community-acquired pneumonia (CAP) is a common respiratory infectious disease.The etiologic diagnosis of CAP remains an uneasy task.Early etiologic diagnosis is critical for proper treatment and might improve the prognosis.So,it is important to identify pathogens causing CAP in early time and accurate way with sensitive and effective method.This paper summarizes the recent progress in the research of the detection assay for CAP.

China ; Humans ; Streptococcus pneumoniae

Objective To explore the relationship between Commitment to Supervisor and Job Satisfaction and investigate the mediating role of psy?chological capital,so as to provide theoretical basis for improving their job satisfaction and promoting physical and mental health. Methods The stratified random sampling method was used to investigate 2 800 police from 7 cities in Liaoning province during the period of August to November 2014(Four questionnaires were carried out under investigation,including questionnaire of personal information,questionnaire of commitment to su?pervisor, questionnaire of psychological capital and questionnaire of job satisfaction),and the effective respondents was 2 193(78.3%). Re?sults Commitment to supervisor was positive associated with job satisfaction(β=0.488,P<0.01),and psychological capital was positive associat?ed with job satisfaction(β=0.552,P<0.01). Commitment to supervisor explained 23.7%of variance in job satisfaction while psychological capital explained 13.6%of variance in job satisfaction. Conclusion Commitment to supervisor and psychological capital have effective predictive value on police’job satisfaction. In addition,the results of study forecast that psychological capital has a mediating effect between commitment tosSupervisor and job satisfaction.