Objective:To explore the phenotypic and genotypic characteristics of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency.Methods:A female patient with FⅪ deficiency and her family members (five individuals from three generations) who presented at Quanzhou First Hospital Affiliated to Fujian Medical University on September 19, 2024 due to diarrhea and fever were selected as study subjects. A retrospective study was conducted to collect the patients′ clinical data. Peripheral venous blood samples were collected from the patient and her family members. Genomic DNA was extracted, followed by sequencing of all exons and flanking sequences of the F11 gene. Candidate variants were validated by Sanger sequencing of the family members, and their pathogenicity was classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Quanzhou First Hospital [Approval No.: Quanyi Lun (2024) K281]. Results:The patient exhibited significantly prolonged activated partial thromboplastin time (APTT) of 80.9 seconds, while FⅪ activity (FⅪ: C) and FⅪ antigen (FⅪ: Ag) levels were extremely low (2% and 3%, respectively). Genetic analysis revealed that the proband harbored homozygous c. 896C>G (p.Thr299Ser) missense variant in exon 9 of the F11 gene, for which her son was heterozygous. The variant was located in a highly conserved domain. Although Mutation Taster predicted it as a polymorphism, SIFT, PolyPhen-2, and LRT analyses suggested it to be likely pathogenic. Protein modeling indicated that the p. Thr299Ser variant may alter the hydrogen bonds between amino acids, thereby affecting the structure and function of the FⅪ protein. According to the ACMG guidelines, c. 896C>G was rated as a likely pathogenic variant (PM1+ PM2_Supporting+ PP1_Strong+ PP3+ PP4). Conclusion:The c. 896C>G (p.Thr299Ser) missense variant of the F11 gene probably underlay the FⅪ deficiency in this pedigree. Above finding has enriched the mutational spectrum of the F11 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

OBJECTIVE: To explore the phenotypic and genotypic characteristics of a Chinese pedigree affected with Hereditary coagulation factor XI (FXI) deficiency. METHODS: A female patient with FXI deficiency and her family members (five individuals from three generations) who presented at Quanzhou First Hospital Affiliated to Fujian Medical University on September 19, 2024 due to diarrhea and fever were selected as study subjects. A retrospective study was conducted to collect the patients' clinical data. Peripheral venous blood samples were collected from the patient and her family members. Genomic DNA was extracted, followed by sequencing of all exons and flanking sequences of the F11 gene. Candidate variants were validated by Sanger sequencing of the family members, and their pathogenicity was classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Quanzhou First Hospital [Approval No.: Quanyi Lun (2024) K281]. RESULTS: The patient exhibited significantly prolonged activated partial thromboplastin time (APTT) of 80.9 seconds, while FXI activity (FXI:C) and FXI antigen (FXI:Ag) levels were extremely low (2% and 3%, respectively). Genetic analysis revealed that the proband harbored homozygous c.896C>G (p.Thr299Ser) missense variant in exon 9 of the F11 gene, for which her son was heterozygous. The variant was located in a highly conserved domain. Although Mutation Taster predicted it as a polymorphism, SIFT, PolyPhen-2, and LRT analyses suggested it to be likely pathogenic. Protein modeling indicated that the p.Thr299Ser variant may alter the hydrogen bonds between amino acids, thereby affecting the structure and function of the FXI protein. According to the ACMG guidelines, c.896C>G was rated as a likely pathogenic variant (PM1+PM2_Supporting+PP1_Strong+PP3+PP4). CONCLUSION The c.896C>G (p.Thr299Ser) missense variant of the F11 gene probably underlay the FXI deficiency in this pedigree. Above finding has enriched the mutational spectrum of the F11 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Adult ; Female ; Humans ; Male ; Middle Aged ; China/ethnology* ; Factor XI/chemistry* ; Factor XI Deficiency/genetics* ; Homozygote ; Pedigree ; Retrospective Studies ; East Asian People/genetics*

Objective:To explore the phenotypic and genotypic characteristics of a Chinese pedigree affected with Hereditary coagulation factor Ⅺ (FⅪ) deficiency.Methods:A female patient with FⅪ deficiency and her family members (five individuals from three generations) who presented at Quanzhou First Hospital Affiliated to Fujian Medical University on September 19, 2024 due to diarrhea and fever were selected as study subjects. A retrospective study was conducted to collect the patients′ clinical data. Peripheral venous blood samples were collected from the patient and her family members. Genomic DNA was extracted, followed by sequencing of all exons and flanking sequences of the F11 gene. Candidate variants were validated by Sanger sequencing of the family members, and their pathogenicity was classified according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Quanzhou First Hospital [Approval No.: Quanyi Lun (2024) K281]. Results:The patient exhibited significantly prolonged activated partial thromboplastin time (APTT) of 80.9 seconds, while FⅪ activity (FⅪ: C) and FⅪ antigen (FⅪ: Ag) levels were extremely low (2% and 3%, respectively). Genetic analysis revealed that the proband harbored homozygous c. 896C>G (p.Thr299Ser) missense variant in exon 9 of the F11 gene, for which her son was heterozygous. The variant was located in a highly conserved domain. Although Mutation Taster predicted it as a polymorphism, SIFT, PolyPhen-2, and LRT analyses suggested it to be likely pathogenic. Protein modeling indicated that the p. Thr299Ser variant may alter the hydrogen bonds between amino acids, thereby affecting the structure and function of the FⅪ protein. According to the ACMG guidelines, c. 896C>G was rated as a likely pathogenic variant (PM1+ PM2_Supporting+ PP1_Strong+ PP3+ PP4). Conclusion:The c. 896C>G (p.Thr299Ser) missense variant of the F11 gene probably underlay the FⅪ deficiency in this pedigree. Above finding has enriched the mutational spectrum of the F11 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.

AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Objective To study the role of ubiquitin-conjugating enzyme 9(UBC9)in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier(SUMO)modification.Methods First,the effects of homocysteine at different concentrations(0 μmol/L,50 μ.mol/L,100 μmol/L,150 μmol/L and 200 μmol/L)on the viability and pyrodeath of mouse macrophages(RAW264.7)were detected by CCK-8 and Western blot.Western blot was used to detect the expression levels of UBC9,SUMO-1,and the inflammatory cytokine IL-1β in different groups of cells.qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9,pyrogen-related protein,and SUMO-1 after RNA interference.Results After stimulation with 100 μmol/L homocysteine,the effect of macrophage activity was minimal,and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression(P＜0.05).Compared with the Control group,the Hcy group's expression of IL-1β and SUMO-1 was increased(P＜0.01).Compared with the Control group,the Hcy group's UBC9 protein and mRNA levels were increased(P＜0.05).The expression of NLRP3,Caspase-1,IL-1β,UBC9,and SUMO-1 was decreased in the si-UBC9+Hcy group compared with the si-NC+Hcy group(P＜0.01).Conclusions Homocysteine induces pyroptosis in macrophages,and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.

OBJECTIVE To investigate the effects of aucubin （AU） on the proliferation and tumor growth of prostate cancer （PC） cells by regulating the protein kinase B （Akt）/murine double minute2 （MDM2）/p53 signaling pathway. METHODS Prostate cancer cell PC3 were separated into control group， 50 μmol/L AU group， 100 μmol/L AU group， SC79 （Akt activator） group （5 μmol/L）， and 100 μmol/L AU+SC79 group. The cell cloning and proliferation ability were investigated； the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected. Meanwhile， xenograft tumor models of nude mice were constructed and separated into tumor group， AU group （80 mg/kg）， SC79 group （50 mg/kg）， and AU+SC79 group （80 mg/kg AU+50 mg/kg SC79）， with 10 mice in each group. They were given relevant medicine， once a day， for 21 d. After the last medication， tumor weight was determined， and the expressions of nucleus-associated antigen （Ki-67） and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue. RESULTS In the cell experiment， compared with control group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50 μmol/L AU and 100 μmol/L AU groups were significantly decreased （P＜0.05）， while the cell apoptosis rate and p53 protein expression levels were significantly increased （P＜0.05）； however， the change trend of each index in SC79 group was opposite （P＜0.05）. Compared with 100 μmol/L AU group， the cell clonal formation number， proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100 μmol/L AU+SC79 group were significantly increased （P＜0.05）， while cell apoptosis rate and p53 protein expression levels were significantly decreased （P＜0.05）； however， compared with SC79 group， the changing trend of indexes was the opposite （P＜0.05）. In the in vivo experiment， compared with the tumor group， the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased （P＜0.05）， and the expression level of p53 protein was significantly increased （P＜0.05）， but the changing trend of above indexes of nude mice in SC79 group were opposite （P＜0.05）. Compared with AU group， the tumor mass， Ki-67 positive expression and phosphorylation levels of Akt and MDM2 protein in tumor tissues of nude mice in AU+SC79 group were significantly increased （P＜0.05）， while the expression level of p53 protein was significantly decreased （P＜0.05）； however， compared with SC79 group， the changing trend of above indexes was opposite （P＜0.05）. CONCLUSIONS AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway.

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.