The proband was a 32-year-old female patient who sought medical attention for over 9 months of pregnancy, reduced fetal movement, and discomfort in the lower abdomen. The proband and her father had normal activated partial thromboplastin time and prothrombin time, decreased fibrinogen activity and antigen levels, and prolonged thrombin time, whereas the test results of her mother were normal. Ultrasonography showed intermuscular vein thrombosis in the left calf of the proband. Peripheral blood DNA was extracted from the proband and her parents, and Sanger sequencing was performed to detect the base sequences of the FGA, FGB, and FGG genes. The proband and her father had heterozygous missense mutations in exon 6 c.615A > C (p. Leu205Phe) and exon 8 c.1121A > C (p. Tyr374Ser) of the FGG gene. Bioinformatics analysis suggested that the two gene mutations may be the pathogenic mechanism of this congenital hypodysfibrinogenemia family.

The proband was a 32-year-old female patient who sought medical attention for over 9 months of pregnancy, reduced fetal movement, and discomfort in the lower abdomen. The proband and her father had normal activated partial thromboplastin time and prothrombin time, decreased fibrinogen activity and antigen levels, and prolonged thrombin time, whereas the test results of her mother were normal. Ultrasonography showed intermuscular vein thrombosis in the left calf of the proband. Peripheral blood DNA was extracted from the proband and her parents, and Sanger sequencing was performed to detect the base sequences of the FGA, FGB, and FGG genes. The proband and her father had heterozygous missense mutations in exon 6 c.615A > C (p. Leu205Phe) and exon 8 c.1121A > C (p. Tyr374Ser) of the FGG gene. Bioinformatics analysis suggested that the two gene mutations may be the pathogenic mechanism of this congenital hypodysfibrinogenemia family.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

Objective:To analyze the F10 gene mutations in a Chinese pedigree affected with the deficiency of the hereditary coagulation factor X (FX), resulting from a new deletion mutation, and to study the associated molecular pathogenesis.Methods:Next generation sequencing (NGS) was performed to screen the genetic mutations in the proband which were then verified by Sanger sequencing. The FX activity (FX∶C) of probands and their family members was detected using the blood clotting method, and the mutation sites of the family members were analyzed using Sanger sequencing. The pathogenicity of the mutation site was predicted by using the online bioinformatics software, Mutation Taster. The SWISS-MODEL software was used for stimulating the three-dimensional models of the wild-type and mutant proteins for analyzing the influence of the mutation site on the structure and function of the proteins, and for analyzing the difference between the catalytic residues of the wild-type and the mutant proteins. The level of the F10 gene mRNA was quantitatively analyzed by qRT-PCR (quantitative reverse transcription polymerase chain reaction) method by constructing plasmids, transfecting human embryonic kidney 293T cells (HEK 293T), and analyzing the splicing of the mutated site by RT-PCR method. The levels of FⅩ∶Ag in cell lysates and cell culture media (both inside and outside the cells) were detected by the ELISA (enzyme linked immunosorbent assay) method.Results:A medium-grade factor X deficiency with a 36.42% FⅩ∶C ratio was detected in the proband by the coagulation method. NGS analysis demonstrated a heterozygous deletion mutation in exon 8:c.902_919del (p.Ala301_Glu306del) in the proband. Sanger sequencing analysis indicated that some members of the family (mother and grandfather) were also carriers of the corresponding deletion mutation. Online bioinformatics software predicted the pathogenic nature of the c.902_919del mutation, with a pathogenic score of 0.999. The 3D protein structure model analysis indicated that the c.902_919del mutation resulted in the disappearance of a segment of β-fold in the protein structure, thereby shortening the preceding segment of the β-fold and a subsequent loss of hydrogen bonds between adjacent amino acids with no significant difference in the side chain conformation of the key catalytic residues compared to the wild-type. mRNA splicing analysis indicated the absence of alternative splicing changes in the mutation, and qRT-PCR results indicated the absence of a statistically significant difference between the mRNA levels of F10 gene and wild-type mRNA in cells expressing c.902_919del mutant. The ELISA results indicated that there was no statistically significant difference in the FX∶Ag levels of the mutant cell culture medium and the lysate.Conclusions:In this pedigree, the heterozygous mutation in exon 8 of F10 gene (c.902_919del, p.Ala301_Glu306del) caused the hereditary factor Ⅹ deficiency.

Beijing Ditan Hospital focuses on improving the core competitiveness of infectious disease discipline talents,fully combines the three mechanisms of ability discovery,ability use and ability development of capacity core management in the mining,use and management of infectious disease discipline talents,establishes the talent cultivation mode of"peace and emergency combination",and practice and exploration are carried out to promote the development and utilization of the potential of the talent team.

Beijing Ditan Hospital focuses on improving the core competitiveness of infectious disease discipline talents,fully combines the three mechanisms of ability discovery,ability use and ability development of capacity core management in the mining,use and management of infectious disease discipline talents,establishes the talent cultivation mode of"peace and emergency combination",and practice and exploration are carried out to promote the development and utilization of the potential of the talent team.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Cox model and Cox model with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95％CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95％CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95％CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95％CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95％CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95％CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95％CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Cox model with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Objective To evaluate the clinical value of adriamycin injection via the foramen ovale and around peripheral trigeminal branches under the guidance of X-ray for treatment of primary trigeminal neuralgia by comparison with the three-dimensional computed tomography (CT).Methods A total of 91 patients with primary trigeminal neuralgia of both sexes,aged 33-76 yr,with the course of disease 6 months-24 yr,with visual analogue scale score of 6-9,were divided into 2 groups using a random number table:X-ray group (n =43) and CT group (n =48).Hartel anterior approach was used to puncture the foramen ovale in 2 groups.One point five percent adriamycin 0.2,0.3 and 0.5 ml were injected via the supraorbital foramen,infraorbital foramen and oval foramen.When pain relief was poor (visual analogue scalc scorc≥ 4) within 1 yr after treatment,oxcarbazepine and adjuncts (tramadol,flupentixol and melitracen tablets,etc.) were taken orally.The requirement for oxcarbazepine and adjuncts was recorded during 1 day-1 week,1 week-1 month,1-3 months,3-6 months and 6 months-1 yr after treatment periods.The operation time,the nuinber of puncture,and developinent and recurrence of complications during treatment and within 1 yr after treatment were recorded.Results Compared with CT group,the number of puncture and incidence of facial hematoma during treatment were significantly increased (P ＜ 0.05 or 0.01),and no significant change was found in the operation time,requirement for oxcarbazepine and adjuncts,incidence of dizziness,nausea and vomiting during treatment,or the incidence and recurrence rate of masticatory muscle weakness and facial numbness after treatment in X-ray group (P＞0.05).Conclusion Compared with the three dimensional CT,X-ray provides similar efficacy and safety when used to guide adriamycin injection via the foramen ovale and around peripheral trigeminal branches for treatment of primary trigeminal neuralgia,showing that X-ray guidance has significant clinical value.

Objective To evaluate the effect of the endotracheal tube (ETT) depth on the efficacy of bronchial blocker when used for one-lung ventilation.Methods Sixty patients of both sexes,aged 46-78 yr,weighing 48-85 kg,with body mass index＜30 kg/m2,scheduled for elective thoracotomy requiring one-lung ventilation,were divided into 2 groups (n =30 each) using a random number table:the distance between the tip of ETT and the carina was 3 cm group (group Ⅰ) and the ETT cuff was placed at 2 cm below the glottis group (group Ⅱ).The bronchial blocker was inserted under the guidance of a fiberoptic bronchoscope.The ETT depth,time to bronchial blocker position,development of bronchial blocker displacement and increase in airway peak pressure,degree of lung collapse,severity of postoperative tracheal mucous membrane injury and development of sore throat and hoarseness were recorded.Results Compared with group Ⅰ,the ETT depth was significantly shallower,the time to bronchial blocker position was shortened,postoperative tracheal mucous membrane injury was attenuated (P＜0.05 or 0.01),and no significant change was found in the incidence of bronchial blocker displacement and increase in airway peak pressure,degree of lung collapse or incidence of sore throat and hoarseness in group Ⅱ (P＞0.05).Conclusion The ETT depth the ETT cuff placed at 2 cm below the glottis can improve the efficacy of bronchial blocker when used for one-lung ventilation.

Objective To explore the diagnostic value of dual syringe and dual-channel direct multi-slice computed tomography venography(MSCTV) for lower extremity deep venous obstructive disease.Methods 100 patients highly suspected deep vein thrombosis by clinic wereunderwent dual syringe and dual-channel direct MSCTV.The original data processed with technology of subtraction,and put into workstation and reconstructed with maximum intensity projection(MIP),multiplanar reformation(MPR) and volume rendering (VR).Images of deep venous obstructive lesions were analysed and graded.All patients were underwent DSA in one week.Results Direct MSCTV showed that the reconstructed images and the vascular contrast were very clear.In the evaluation of deep venous,excellent proportion was 95 ％ for the inferior vena cava,94 ％ for the common iliac vein,95 ％ for the external iliac vein,95.5 ％ for the femoral vein,96.5％ for the popliteal vein and 92 ％ for the low leg vein.Direct MSCTV displayed complete and regular vein in 8 normal patients,92 cases displayed different parts and different degrees of thrombosis.On original axial images,eccentric filling defect of vascular were showed (there were 64 multiple vein occlusion cases and 28 solitary obstruction cases).The occlusion locations in deep venous were as following:3 in the inferior vena cava,67 in the common iliac vein,28 in the external iliac vein,50 in the femoral vein,26 in the popliteal vein,89 in the anterior tibial vein,35 in the posterior tibial vein and 5 in the peroneal vein.There were 7 normal patients and 93 patients with different parts and different degrees of thrombosis.Conclusion Direct MSCTV can accurately show deep vein thrombosis,which image is clear and reliable for displaying the scope and extent of lesions of the vascular and whether the collateral circulation established.Direct MSCTV has a significant clinical value in diagnosing the thrombotic disease of deep vein obstructive lesions.