Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.

Objective To assess the marginal microleakage of specimens following aging simulation of adhesive restorations for dental defects using methacryloxylethyl cetyldimethyl ammonium chloride(DMAE-CB)and nanoparticles of amorphous calcium phosphate(NACP)binder.Methods DMAE-CB and NACP were synthesized in the laboratory.Eight groups were formed by varying the mass fraction ratios of the two components in the adhesive according to previous experiments,A:binder+3％DMAE-CB+25％NACP,B:binder+4％DMAE-CB+35％NACP,C:binder+1％DMAE-CB+15％NACP,D:binder+4％DMAE-CB+15％NACP,E:binder+1％DMAE-CB+35％NACP,F:binder+3％DMAE-CB,G:binder+25％NACP,H:SBMP binder as the control group.Forty human third molars were collected and randomly divided into 8 groups to prepare standardized Class Ⅱ preparations.Subsequent-ly,dental defect adhesive restoration specimens were made by using the 8 groups of binder,and aging simulation was performed through thermal cycling.After thermal cycling,the specimens were immersed in the dye solution.Each specimen was sectioned into 4 parts of dentin tissue slices along the gingival,proximal,and occlusal walls using a low-speed cutting machine,and the depth of dye penetration was observed under a stereomicroscope and recorded according to a unified standard for microleakage level.Finally,one randomly selected adhesive specimen from each of the 8 groups was subjected to gold sputtering and observed under scanning electron microscopy(SEM)to measure the gap width between the resin and dental tissue.Results Penetration staining showed that there were no statistically significant differences in the depth of marginal microleakage between the experimental and control groups on the gingival and occlusal walls(P＞0.05).However,there was a statistically significant difference in microleakage depth between the gingival and occlusal walls(P＜0.05).Scanning electron microscopy(SEM)results,after averaging particle size measurements,revealed no statistically significant differences in the gap width between the filling restorations and dental hard tissues between the experimental and con-trol groups(P＞0.05).Conclusion Dentin adhesives modified with DMAE-CB and NACP increase antibacterial and remineralization properties without affecting marginal microleakage in adhesive restorations,providing reliable theoretical support for their clinical appli-cation.

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

Objective To comparatively analyze the friction wear performance,fracture resistance,and displacement resistance before and after aging of full crowns made from PEEK,cobalt-chromium alloy,and zirconia,providing a theoretical basis for the future application of PEEK in crown fabrication.Methods Standard anatomical full crowns of PEEK,cobalt-chromium alloy,and zirconia were fabricated by preparing the upper first premolar and taking silicone rubber impressions,resulting in 25 crowns of each material.The crowns were divided into three groups:Group A(15 crowns,5 from each material),Group B(30 crowns,10 from each materi-al),and Group C(30 crowns,10 from each material,serving as a control).Group A underwent 120 000 chewing simulations under simulated oral physiological conditions,using a stereomicroscope and Micro-image Analysis & Process system to assess and compare wear of antagonists(opposing talc ceramic balls)and material wear.Group B underwent 10 000 thermal cycling aging tests and Group C were served as the control.Universal testing machines were used to evaluate and compare the fracture resistance and displacement re-sistance of Groups B and C.Results ①The wear heights of full crown materials were as follows:cobalt-chromium alloy(0.61±0.05)mm,zirconia(0.81±0.07)mm,and PEEK(0.96±0.04)mm,with PEEK＞zirconia＞cobalt-chromium alloy(P＜0.05).For antagonist wear,the wear heights were cobalt-chromium alloy＞zirconia＞PEEK(P＜0.05).②The fracture resistance of cobalt-chromium alloy be-fore and after aging was(3 665.645±71.166)N and(2 906.830±225.143)N,respectively;for zirconia it was(2 447.825±316.961)N and(1 829.229±72.046)N;and for PEEK crowns it was(1 632.378±53.046)N and(1 074.872±105.491)N,showing cobalt-chromi-um alloy＞zirconia＞PEEK(P＜0.05).The displacement resistance for cobalt-chromium alloy before and after aging was(1 604.630±95.680)N and(1 092.137±77.869)N;for zirconia it was(1 768.851±56.273)N and(1 381.618±62.326)N;and for PEEK crowns it was(1 148.811±70.417)N and(931.723±64.454)N,indicating zirconia＞cobalt-chromium alloy＞PEEK(P＜0.05).The aging degradation of cobalt-chromium alloy's fracture and displacement re-sistance was(758.815±157.734)N and(512.492±34.530)N,re-spectively;for zirconia,it was(618.597±251.281)N and(387.233±7.947)N;and for PEEK crowns,it was(557.506±61.950)N and(217.089±14.589)N,with anti-aging performance:PEEK＞zirconia＞cobalt-chromium alloy(P＜0.05).Conclusion The wear re-sistance,fracture resistance,and displacement resistance of PEEK meet the clinical standards for full crown materials,and PEEK demonstrates good anti-aging performance while effectively protecting opposing teeth.Therefore,PEEK has the potential to become a novel material for full crown fabrication.

Objective To comparatively analyze the friction wear performance,fracture resistance,and displacement resistance before and after aging of full crowns made from PEEK,cobalt-chromium alloy,and zirconia,providing a theoretical basis for the future application of PEEK in crown fabrication.Methods Standard anatomical full crowns of PEEK,cobalt-chromium alloy,and zirconia were fabricated by preparing the upper first premolar and taking silicone rubber impressions,resulting in 25 crowns of each material.The crowns were divided into three groups:Group A(15 crowns,5 from each material),Group B(30 crowns,10 from each materi-al),and Group C(30 crowns,10 from each material,serving as a control).Group A underwent 120 000 chewing simulations under simulated oral physiological conditions,using a stereomicroscope and Micro-image Analysis & Process system to assess and compare wear of antagonists(opposing talc ceramic balls)and material wear.Group B underwent 10 000 thermal cycling aging tests and Group C were served as the control.Universal testing machines were used to evaluate and compare the fracture resistance and displacement re-sistance of Groups B and C.Results ①The wear heights of full crown materials were as follows:cobalt-chromium alloy(0.61±0.05)mm,zirconia(0.81±0.07)mm,and PEEK(0.96±0.04)mm,with PEEK＞zirconia＞cobalt-chromium alloy(P＜0.05).For antagonist wear,the wear heights were cobalt-chromium alloy＞zirconia＞PEEK(P＜0.05).②The fracture resistance of cobalt-chromium alloy be-fore and after aging was(3 665.645±71.166)N and(2 906.830±225.143)N,respectively;for zirconia it was(2 447.825±316.961)N and(1 829.229±72.046)N;and for PEEK crowns it was(1 632.378±53.046)N and(1 074.872±105.491)N,showing cobalt-chromi-um alloy＞zirconia＞PEEK(P＜0.05).The displacement resistance for cobalt-chromium alloy before and after aging was(1 604.630±95.680)N and(1 092.137±77.869)N;for zirconia it was(1 768.851±56.273)N and(1 381.618±62.326)N;and for PEEK crowns it was(1 148.811±70.417)N and(931.723±64.454)N,indicating zirconia＞cobalt-chromium alloy＞PEEK(P＜0.05).The aging degradation of cobalt-chromium alloy's fracture and displacement re-sistance was(758.815±157.734)N and(512.492±34.530)N,re-spectively;for zirconia,it was(618.597±251.281)N and(387.233±7.947)N;and for PEEK crowns,it was(557.506±61.950)N and(217.089±14.589)N,with anti-aging performance:PEEK＞zirconia＞cobalt-chromium alloy(P＜0.05).Conclusion The wear re-sistance,fracture resistance,and displacement resistance of PEEK meet the clinical standards for full crown materials,and PEEK demonstrates good anti-aging performance while effectively protecting opposing teeth.Therefore,PEEK has the potential to become a novel material for full crown fabrication.

Objective To assess the marginal microleakage of specimens following aging simulation of adhesive restorations for dental defects using methacryloxylethyl cetyldimethyl ammonium chloride(DMAE-CB)and nanoparticles of amorphous calcium phosphate(NACP)binder.Methods DMAE-CB and NACP were synthesized in the laboratory.Eight groups were formed by varying the mass fraction ratios of the two components in the adhesive according to previous experiments,A:binder+3％DMAE-CB+25％NACP,B:binder+4％DMAE-CB+35％NACP,C:binder+1％DMAE-CB+15％NACP,D:binder+4％DMAE-CB+15％NACP,E:binder+1％DMAE-CB+35％NACP,F:binder+3％DMAE-CB,G:binder+25％NACP,H:SBMP binder as the control group.Forty human third molars were collected and randomly divided into 8 groups to prepare standardized Class Ⅱ preparations.Subsequent-ly,dental defect adhesive restoration specimens were made by using the 8 groups of binder,and aging simulation was performed through thermal cycling.After thermal cycling,the specimens were immersed in the dye solution.Each specimen was sectioned into 4 parts of dentin tissue slices along the gingival,proximal,and occlusal walls using a low-speed cutting machine,and the depth of dye penetration was observed under a stereomicroscope and recorded according to a unified standard for microleakage level.Finally,one randomly selected adhesive specimen from each of the 8 groups was subjected to gold sputtering and observed under scanning electron microscopy(SEM)to measure the gap width between the resin and dental tissue.Results Penetration staining showed that there were no statistically significant differences in the depth of marginal microleakage between the experimental and control groups on the gingival and occlusal walls(P＞0.05).However,there was a statistically significant difference in microleakage depth between the gingival and occlusal walls(P＜0.05).Scanning electron microscopy(SEM)results,after averaging particle size measurements,revealed no statistically significant differences in the gap width between the filling restorations and dental hard tissues between the experimental and con-trol groups(P＞0.05).Conclusion Dentin adhesives modified with DMAE-CB and NACP increase antibacterial and remineralization properties without affecting marginal microleakage in adhesive restorations,providing reliable theoretical support for their clinical appli-cation.

Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.

Objective To search,evaluate,and integrate the best evidence on the safety and accuracy of peripherally inserted central catheter(PICC)tip positioning in intracardiac ECG so as to provide evidence-based support for clinical practice.Methods Following the"6S"evidence resource pyramid model,evidence was systematically searched from top to bottom across databases,such as BMJ Best Practice,UpToDate,National Institute for Health and Care Excellence,Guidelines International Network,Scottish Intercollegiate Guidelines Network,Registered Nurses'Association of Ontario,JBI(Joanna Briggs Institute)Evidence-Based Healthcare Database,PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,SinoMed and VIP Database.The search period was from the inception the database to 1st February,2024.Two researchers independently evaluated the quality of the literature and extracted evidence that met the criteria.Results A total of 12 articles were retrieved including 2 guidelines,1 group standard,1 expert consensus,1 Meta-analysis,1 systematic review,3 randomised controlled trials,1 diagnostic study and 2 cohort studies.They covered 6 themes such as pre-catheterisation assessment and preparation,the best tip position and waveform for adults,the best tip position and waveform for neonates,the best tip position and waveform for patients with atrial fibrillation,maintaining waveform stability during catheterisation and relevant information recording during the catheterisation process.A total of 22 pieces of evidence were summarised from the documents.Conclusion This study summarises the best evidence in the safety and accuracy of PICC tip positioning techniques of intracardiac ECG,which can provide a basis for nursing staff to practice evidence-based nursing.

ObjectiveTo explore the protective effect of polysaccharide from Inonotus obliquus （IOP） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodA total of 40 male C57BL/6 mice were randomly divided into normal group， model group， dexamethasone group， and high-dose and low-dose IOP groups， with eight mice in each group. The high-dose and low-dose IOP groups were administered intragastrically with IOP at 20 and 10 mg·kg^-1， respectively. The normal group and the model group were intragastrically administered with normal saline in equal volumes， and the dexamethasone group was intraperitoneally injected with dexamethasone phosphate injection of 30 mg·kg^-1 for 21 days. An ALI mouse model induced by LPS was constructed， and hematoxylin-eosin （HE） staining， immunofluorescence staining， and blood routine were used to detect pathological damage of lung tissue and blood cell content. Enzyme-linked immunosorbent assay （ELISA） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression levels of various inflammatory factors. Changes in gut microbiota and plasma differential metabolites in mice were detected using 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the model group， the lung tissue lesions of ALI mice were significantly improved after IOP administration， and the spleen and thymus index were dramatically increased （P<0.05， P<0.01）. The ratio of wet-to-dry weight of lung tissue was sensibly decreased （P<0.05， P<0.01）， and the number of lymphocytes was substantially increased （P<0.05， P<0.01）. The number of neutrophils was markedly decreased （P<0.01）. The expression level of interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-1β （IL-1β）， nuclear factor-κB（NF-κB）， and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） decreased prominently （P<0.05， P<0.01） and the expression level of interleukin-10 （IL-10） increased memorably （P<0.01）. The 16S rRNA sequencing results show that IOP can regulate and improve intestinal microbial disorders. The UPLC-Q-TOF-MS results indicate that the treatment of ALI mice with IOP may involve pathways related to mitochondrial， sugar， and amino acid metabolism， such as nucleotide sugar metabolism， histidine metabolism， ubiquinone， and other terpenoid compound-quinone biosynthesis， as well as starch and sucrose metabolism. ConclusionThe improvement of lung tissue lesions and inflammatory response by IOP in ALI mice may be related to maintaining intestinal microbiota balance， regulating mitochondrial electron oxidation respiratory chain， as well as sugar and amino acid metabolism pathways， and affecting the production of related microbial metabolites and tricarboxylic acid cycle metabolites.

OBJECTIVE: To explore the molecular pathogenesis of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency due to variants of the F11 gene. METHODS: A male proband with Hereditary coagulation factor Ⅺ deficiency who was admitted to the First Affiliated Hospital of Wenzhou Medical University due to urinary calculi on November 30, 2020 and his family members (7 individuals from 3 generations in total) were selected as the study subjects. Clinical data of the proband were collected, and relevant coagulation indices of the proband and his family members were determined. Genomic DNA of peripheral blood samples was extracted for PCR amplification. All exons, flanking sequences, and 5' and 3' untranslated regions of the F11 gene of the proband were analyzed by direct sequencing. And the corresponding sites were subjected to sequencing in other family members. The conservation of amino acid variation sites was analyzed by bioinformatic software, and the effect of the variant on the protein function was analyzed. Variants were graded based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The proband was a 36-year-old male. His activated partial thromboplastin time (APTT) was 89.2s, which was significantly prolonged. The FⅪ activity (FⅪ:C) and FⅪ antigen (FⅪ:Ag) were 2.0% and 3.5%, respectively, which were extremely reduced. Both the proband and his sister were found to harbor compound heterozygous variants of the F11 gene, including a c.689G>T (p.Cys230Phe) missense variant in exon 7 from their father and a c.1556G>A (p.Trp519*) nonsense variant in exon 13 from their mother. Conservation analysis indicated the Cys230 site to be highly conserved. The c.1556G>A (p.Trp519*) variant was known to be pathogenic, whilst the c.689G>T variant was classified as likely pathogenic (PM2+PM5+PP1+PP3+PP4) based on the ACMG guidelines. CONCLUSION The c.689G>T and c.1556G>A compound heterozygous variants of the F11 gene probably underlay the pathogenesis of FⅪ deficiency in this pedigree.
Adult ; Humans ; Male ; 3' Untranslated Regions ; East Asian People ; Factor XI/genetics* ; Factor XI Deficiency/genetics* ; Partial Thromboplastin Time ; Pedigree