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

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

Aim To investigate the effect of irisin on endothelial inflammation and atherosclerosis(As)in mice.Methods ApoE-/-mice were randomly divided into control group,As model group,and irisin group(treated with irisin based on the As model),with 10 mice in each group.The carotid tissues were stained using pathological techniques and immunofluorescence.Human aortic endothelial cells(HAEC)were cultured in vitro,treated with irisin,and stimulated with cholesterol crystal(CC).The protein levels of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were then detected by Western blot.The expression of inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and chemokine(C-C motif)ligand 2(CCL2)were detected by RT-qPCR.The ad-hesion of monocytes was assessed using cell adhesion assay.Results The carotid plaque area in the mice of As model group was significantly increased compared with that in control group(P＜0.05).In contrast,the plaque area was re-duced in the irisin group compared with the As model group(P＜0.05).Compared with the control group,the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC were increased in the carotid arteries of the As model group(P＜0.05),while irisin could reduce the expression of VCAM-1,the number of CD68+macrophages,and the deposition of CC(P＜0.05).At the in vitro level,the expression of VCAM-1 and ICAM-1,as well as the adhesion of monocytes in CC-stimulated HAEC,were increased(P＜0.05).However,irisin could inhibit the increased expression of VCAM-1 and ICAM-1(P＜0.05),as well as the adhesion of monocytes induced by CC(P＜0.05).The mRNA levels of IL-1β,IL-6 and CCL2 in HAEC of CC stimulated group were increased(P＜0.05),while irisin could inhibit the mRNA expressions of IL-1β,IL-6 and CCL2 induced by CC(P＜0.05).Conclusion Irisin can inhibit vascular inflamma-tion,thereby reducing the occurrence and progression of atherosclerosis.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

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:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

OBJECTIVE To explore the safety， effectiveness， and cost-effectiveness of elderly patients with sarcopenia receiving Shenling baizhu powder combined with nutrition and exercise intervention， providing a reference for rational clinical drug use. METHODS A total of 237 elderly sarcopenia patients were randomly assigned to an observation group （118 cases） and a control group （119 cases）. Both groups of patients received nutrition and exercise intervention； the observation group added Shenling baizhu powder （6 g each time， three times daily） on this basis. The safety， effectiveness， and cost-effectiveness of the two plans were compared after 3 months. RESULTS Both groups of patients completed the follow-up. Before intervention， no significant difference was observed in skeletal muscle index （SMI）， grip strength， and 6-minute walk test （6MWT） speed between the two groups （P＞0.05）. After intervention， the grip strength of the patients in the observation group was significantly greater than that of the control group （25.05 kg vs. 23.18 kg， P＜0.01）； the treatment response rate of sarcopenia， SMI， and 6MWT speed were higher than those of the control group， butthe differences were not statistically significant （P＞0.05）. The adverse reaction/event rate of the patients in the observation group was lower than that of the control group （14.41% vs. 16.81%， P＝0.611）， but the difference was not statistically significant. Compared with the control group’s plan， the cost of the observation group’s plan was higher （981.25 yuan vs. 913.94 yuan）， and the effect was better （effectiveness rate： 0.618 6 vs. 0.563 0）， with an incremental cost-effectiveness ratio of 1 210.61 yuan. The results of the sensitivity analysis were consistent with the cost-effectiveness analysis results. CONCLUSION Elderly patients with sarcopenia who receive Shenling baizhu powder combined with nutrition and exercise intervention can significantly strengthen grip strength without increasing the incidence of adverse reactions/events. Compared with the control group plan， the observation group needs to spend an additional 1 210.61 yuan for each additional effective patient with sarcopenia.

Objective:To analyze the Helicobacter pylori ( Hp) infection status in patients with colorectal polyp, and to study the relationship between the clinical features of colonoscopy and the Hp infection. Methods:The clinical data of 637 patients underwent colonoscopy from January to December 2022 in Dalian Central Hospital of Dalian University of Technology were retrospectively analyzed. The Hp infection status was detected by 14C-urea breath test. The relevant clinical data were recorded including age, gender, body mass index (BMI), total cholesterol (TC), triacylglycerol (TG), smoking history, Hp infection status, polyp diameter, polyp number, polyp location and polyp pathological classification. Multivariate Logistic regression was used to analyze the independent risk factors of colorectal polyp. Results:Among the 637 patients, 437 patients suffered from colorectal polyp (colorectal polyp group), and 200 patients had no colorectal polyp (control group). There were no statistical difference in age, TC and smoking history between two groups ( P>0.05); the male proportion, BMI, TG and Hp infection rate in colorectal polyp group were significantly higher than those in control group: 57.44% (251/437) vs. 35.00% (70/200), (24.34 ± 3.24) kg/m 2 vs. (23.70 ± 3.40) kg/m 2, 1.47 (0.93, 1.75) mmol/L vs. 1.31 (0.86, 1.63) mmol/L and 54.46% (238/437) vs. 40.00% (80/200), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that gender and Hp infection were independent risk factors of colorectal polyp ( OR = 2.260 and 1.545, 95% CI 1.568 to 3.258 and 1.082 to 2.208, P<0.01 or <0.05). Among the 437 patients in the colorectal polyp group, Hp infection was in 238 cases, and non- Hp infection was in 199 cases. There was no statistical difference in polyp location between Hp infection patients and non- Hp infection patients ( P>0.05); the rates of polyp diameter ≥0.5 cm, multiple polyp and adenomatous polyp in Hp infection patients were significantly higher than those in non- Hp infection patients: 66.81% (159/238) vs. 53.27% (106/199), 55.04% (131/238) vs. 36.68% (73/199) and 67.23% (160/238) vs. 54.77% (109/199), and there were statistical differences ( P<0.01). Conclusions:Hp infection is an important pathogenic factor for colorectal polyp. Hp infection is associated with some clinical features of colorectal polyp.

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