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 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 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 Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective:To investigate the effect of water intake on bladder filling time before embryo transfer.Methods:A total of 189 patients were collected from February to June 2023 who were to undergo embryo transfer in Guangdong Women and Children Hospital. The patients were divided into group A ( n=61), group B ( n=64) and group C ( n=64) using a random number table and they were respectively given 300 mL, 500 mL and 700 mL water to drink. Abdominal ultrasound was performed every 15 min, a total of 1-5 times, from 45 min after drinking water until the bladder filling. The bladder filling time and bladder volume were collected. Kaplan-Meier method was used to compare the difference of bladder filling time among the three groups. The multivariate Cox regression was used to analyze factors of bladder filling time. Results:The cumulative bladder filling rates of group A, group B and group C at 105 min after drinking water were 57.4% (35/61), 90.6% (58/64) and 98.4% (63/64), respectively, and the median survival time (95% CI) of bladder filling was 105.0 (89.9-120.1) min, 60.0 (55.4-64.7) min and 60.0 (55.4-64.6) min, respectively. Pairwise comparison of Kaplan-Meier analysis revealed that the bladder filling time of group A was longer than that of group B and group C ( P<0.001), and there was no statistically significant difference between group B and group C ( P>0.05). The results of age-stratification analysis showed that the bladder filling time of younger patients in group A [90.0 (75.2-104.8) min] was longer than that in group B [60.0 (55.8-64.2) min, P<0.001] and group C [60.0 (55.1-64.8) min, P<0.001], and there was no statistical significance between group B and group C ( P>0.05); the bladder filling time of older patients in group C [60.0 (59.1-70.9) min] was shorter than that in group A [105.0 (89.9-120.1) min, P<0.001] and group B [75.0 (64.3-85.7) min, P=0.027], there was no statistical significance between group A and group B ( P>0.05). Multivariate Cox regression analysis showed that taking group A as reference, the hazard ratio ( HR, 95% CI) of groups B and C were 2.71 (1.78-4.21) and 3.23 (2.10-4.96), both P<0.001. The HR (95% CI) of the elderly patients was 0.69 (0.49-0.99), P=0.044. Conclusion:Water intake and age are independent factors affecting bladder filling time in embryo transfer patients. Patients are recommended to drink 500 mL of water 75 min before embryo transfer and appropriately increase the amount of water or extend the bladder preparation time after drinking water for elderly patients.

Objective:To investigate the effect of water intake on bladder filling time before embryo transfer.Methods:A total of 189 patients were collected from February to June 2023 who were to undergo embryo transfer in Guangdong Women and Children Hospital. The patients were divided into group A ( n=61), group B ( n=64) and group C ( n=64) using a random number table and they were respectively given 300 mL, 500 mL and 700 mL water to drink. Abdominal ultrasound was performed every 15 min, a total of 1-5 times, from 45 min after drinking water until the bladder filling. The bladder filling time and bladder volume were collected. Kaplan-Meier method was used to compare the difference of bladder filling time among the three groups. The multivariate Cox regression was used to analyze factors of bladder filling time. Results:The cumulative bladder filling rates of group A, group B and group C at 105 min after drinking water were 57.4% (35/61), 90.6% (58/64) and 98.4% (63/64), respectively, and the median survival time (95% CI) of bladder filling was 105.0 (89.9-120.1) min, 60.0 (55.4-64.7) min and 60.0 (55.4-64.6) min, respectively. Pairwise comparison of Kaplan-Meier analysis revealed that the bladder filling time of group A was longer than that of group B and group C ( P<0.001), and there was no statistically significant difference between group B and group C ( P>0.05). The results of age-stratification analysis showed that the bladder filling time of younger patients in group A [90.0 (75.2-104.8) min] was longer than that in group B [60.0 (55.8-64.2) min, P<0.001] and group C [60.0 (55.1-64.8) min, P<0.001], and there was no statistical significance between group B and group C ( P>0.05); the bladder filling time of older patients in group C [60.0 (59.1-70.9) min] was shorter than that in group A [105.0 (89.9-120.1) min, P<0.001] and group B [75.0 (64.3-85.7) min, P=0.027], there was no statistical significance between group A and group B ( P>0.05). Multivariate Cox regression analysis showed that taking group A as reference, the hazard ratio ( HR, 95% CI) of groups B and C were 2.71 (1.78-4.21) and 3.23 (2.10-4.96), both P<0.001. The HR (95% CI) of the elderly patients was 0.69 (0.49-0.99), P=0.044. Conclusion:Water intake and age are independent factors affecting bladder filling time in embryo transfer patients. Patients are recommended to drink 500 mL of water 75 min before embryo transfer and appropriately increase the amount of water or extend the bladder preparation time after drinking water for elderly patients.

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 Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.