China has the highest mortality rate from cardiovascular disease in the world and coronary artery disease (CAD) is the leading cause of death from cardiovascular disease. The cost of treatment for CAD is high, which is related to the incidence of CAD and possible irrational treatment protocols. However, with the escalating costs of healthcare in most countries, the cost-effectiveness of diagnostic and management testing is increasingly important. Many studies have shown that most non-invasive tests are more cost-effective than coronary angiography (CAG). This article reviews the cost-effectiveness of MPI compared with CAG and other non-invasive tests.

Objective:To evaluate the efficacy and safety of endoscopic ultrasound-guided selective varices devascularization (EUS-SVD) for the treatment of esophagogastric varices.Methods:A total of 43 cases of liver cirrhosis with esophageal and gastric varices at the First Affiliated Hospital of Anhui Medical University from February to December 2021 were included in a retrospective cohort study. The cases were divided into two treatment groups based on endoscopic treatment: EUS-SVD group ( n=22) and conventional endoscopic sclerosant injection group (conventional gastroscopy group, n=21). The doses of sclerosants and tissue glue, effective rate of esophageal varice treatment within 2 months after surgery, rebleeding rate within 3 months after surgery, and adverse reactions were compared. Results:The differences in terms of mean patient age, gender composition, etiology of liver cirrhosis, Child-Pugh classification of liver function, classification of esophageal varices, composition of endoscopic treatment indications, and mean maximum diameter of gastric varices were not statistically significant between the two groups ( P>0.05), indicating the comparability of baseline data. Perforating veins outside the gastric wall of gastric varices could be detected during the procedure in the EUS-SVD group, and disappearance of gastric varices after injection treatment could be determined, while these two indicators could not be detected in the conventional gastroscopy group. The amounts of sclerosing agents and tissue adhesives used in the EUS-SVD group were 7.54±3.10 mL and 1.30±0.57 mL, respectively, while the corresponding amounts in the conventional gastroscopy group were 7.57±3.50 mL ( t=0.026, P=0.980) and 1.38±0.67 mL ( t=-0.452, P=0.654), respectively. The effective treatment rate for esophageal varice within 2 months after surgery was 63.6% (14/22) in the EUS-SVD group and 52.4% (11/21) in the conventional gastroscopy group, but the difference was not statistically significant ( χ2=0.559, P=0.455). The rebleeding rate within 3 months after surgery was 4.5% (1/22) in the EUS-SVD group, significantly lower than the rate of 33.3% (7/21) in the conventional gastroscopy group ( P=0.021). Neither group experienced events of ectopic embolism or death. There was no statistically significant difference between the two groups in terms of postoperative pain, fever, nausea and vomiting, or rebleeding rate within 72 hours after surgery ( P>0.05). The incidence of gastric fundus ulcers was 9.1% (2/22) in the EUS-SVD group, significantly lower than the rate of 42.9% (9/21) in the conventional gastroscopy group ( χ2=6.435, P=0.011). Conclusion:EUS-SVD treatment for esophagogastric varices is safe and effective. It can clearly display the deep-seated intramural vessels of the gastric wall, measure the diameter of the blood vessels, accurately inject tissue glue, occlude the varicose veins and perforating vessels, and reduce the occurrence of postoperative ulcers and rebleeding.

The online and offline hybrid teaching model of evidence-based medicine (EBM) is currently in the stage of development. Previous teaching focused on the teaching process in the classroom, and did not organically combine all the course contents before, during, and after class. The BOPPPS model can be used to establish coherence and integrity in the EBM teaching process. Considering the discipline characteristics and teaching objectives of EBM, this study initially explored and designed a BOPPPS-based online and offline hybrid teaching model. Taking the "diagnostic evidence" module as an example, the teaching implementation details were introduced. A pre-designed questionnaire was used to conduct baseline survey and follow-up survey on students before and after class to evaluate the teaching model and effect. The surveys showed that half of the students (77/154) preferred the new online and offline hybrid teaching model of EBM. The students found that all aspects of BOPPPS teaching were generally acceptable and satisfactory. Compared with before teaching, the students' proficiency in EBM was significantly improved after the teaching ( P<0.001), particularly in their ability to retrieve literature and evaluate the quality of evidence, which is of great significance for expanding their knowledge and clinical thinking.

OBJECTIVE: To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis. METHODS: Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model. RESULTS: Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants. CONCLUSION Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.
Humans ; Male ; Amino Acids ; East Asian People ; Exons ; Pedigree ; Retrospective Studies ; Afibrinogenemia/genetics* ; Mutation, Missense ; Fibrinogen/genetics*

Objective:To observe the inhibitory effects of Huangqi Jiedu Decoction on lung metastasis of breast cancer in nude mice; To explore the mechanism of intervening epithelial mesenchymal transformation (EMT) induced by Wnt/β-catenin signaling pathway.Methods:Totally 30 nude mice were divided into model group, adriamycin group and Huangqi Jiedu Decoction low-, medium-, and high-dosage groups according to random number table method. Each group was injected subcutaneously with mouse breast cancer 4T1 cells to construct tumor - bearing nude mice model. Huangqi Jiedu Decoction low-, medium- and high-dosage groups were intragastrically administrated with Huangqi Jiedu Decoction 17.82, 35.64 and 71.28 g/kg; adriamycin group was injected intraperitoneally adriamycin 0.05 g/kg; model group was intragastrically administrated with normal saline of the same volume for 21 d. Tumor volume was measured at 9, 15, and 21 days after modeling. After the end of administration, the tumor tissue was separated, the tumor weight was measured, and the tumor inhibition rate was calculated. The lung tissue was Isolated,, the number of lung metastatic nodules and the inhibition rate of lung metastasis was counted. HE staining was used to observe the tissue morphology and evaluate the effectiveness of the model. The protein expressions of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by Western Blot. The mRNA levels of β-catenin, E-Cadherin and Vimentin in lung tissue were detected by real-time fluorescent quantitative PCR.Results:Compared with the model group, the tumor volume and mass of Huangqi Jiedu Decoction low-, medium- and high-dosage groups decreased ( P<0.01); the number of pulmonary metastasis nodules in Huangqi Jiedu Decoction high-dosage group significantly decreased ( P<0.01); the mRNA and protein expressions of β-catenin and Vimentinm decreased in the Huangqi Jiedu Decoction low-, medium- and high-dosage groups ( P<0.01), and the protein and mRNA expressions of E-Cadherin increased in the Huangqi Jiedu Decoction high-dosage group ( P<0.01). Conclusion:Huangqi Jiedu Decoction can effectively inhibit the growth and lung metastasis of breast cancer transplanted tumor, and the mechanism may be to down-regulate the expression of key molecules in the Wnt/β-catanin signaling pathway, thereby inhibiting the EMT process, so as to inhibit the lung metastasis of breast cancer.

Objective:To analyze 12 antithrombins (AT) gene mutations that cause AT deficiency and discuss the relationship between the SERPINC1 gene. mutations and venous thrombotic events.Methods:This study belongs to case series of observational studies. Collected the clinical data of 12 AT deficiency cases in the First Affiliated Hospital of Wenzhou Medical University from April 2014 to April 2021 and collected the blood samples before treatment. The AT activity (AT: A) and AT antigen (AT: Ag) was detected by chromogenic substrate and immunoturbidimetry, respectively. The 7 exons and flanking sequences of the SERPINC1 gene were sequenced directly by PCR, the suspected mutations were validated by reverse sequencing. Analyzed the correlation between the SERPINC1 gene. mutations and venous thrombotic events and figured out the proportion.Results:The AT: A of the 12 patients all decreased significantly, ranging from 30% to 66%, and the AT: Ag of the 7 patients decreased accordingly, showing type Ⅰ AT deficiency, and the AT: Ag of the other 5 patients were normal, presented type Ⅱ AT deficiency. 12 mutations were found including 6 heterozygous mutations which were discovered for the first time: c.456_458delCTT(p.phe121del), c.318_319insT(p.Asn75stop), c.922G>T(p.Gly276Cys), c.938T>C (p.Met281Thr), c.1346T>A(p.Leu417Gln)and c.851T>C(p.Met252Thr). All 12 patients had venous thrombosis, and 3 cases including 2 compound heterozygotes and 1 single heterozygote all suffered from deep venous thrombosis (DVT) when they were younger without obvious triggers. The other 9 patients all combined with the other thrombotic factors including old age, hypertensive, smoking, pregnancy, and prolonged immobilization.Conclusion:Patients with AT deficiency caused by SERPINC1 gene defects are prone to venous thrombosis, especially combined with other thrombotic factors.

Objective:To explore the effect of distal veins on the survival of a dorsal four-territory perforator flap in rats.Methods:A total of 32 SD rats were randomly divided into the control group and the experimental group, with 16 rats in each group. The multi-territory perforator flap including the bilateral iliolumbar and bilateral posterior intercostal angiosomes was cut from the back of each rat, with the size of 6 cm×7 cm. The right iliolumbar artery and vein were preserved in the control group, while the right iliolumbar artery and the right posterior intercostal vein were preserved in the experimental group. In both groups, incisions were made between the right iliolumbar angiosome and the right posterior intercostal angiosome. Finally, the flap was sutured back to their orthotopic site. At 6 hours and 1, 3, 5, 7 days after surgery, the blood perfusion at the bilateral iliolumbar and the left posterior intercostal vascular territories were measured. On the seventh day after surgery, the percentage of the survived area of the flaps were evaluated, arteriography was performed to observe the dilation of arteries within the flap, the intraluminal diameter of the choke artery in the choke 2 area was measured using hematoxylin and eosin staining, and the relative expression of endothelial nitric oxide synthase (eNOS) was detected by Western blotting. SPSS 28.0 was used for statistical analysis, and measurement data were presented as Mean±SD. Independent sample t-test was used to compare data across two groups. P<0.05 was considered statistically significant. Results:(1) At 6 hours and 1, 3, 5, 7 days after surgery, the experimental group displayed higher blood perfusion than the control group at the bilateral iliolumbar and the left posterior intercostal vascular territories (all P<0.01). (2) On the 7th day after surgery, the artery dilation of the experimental group was more obvious than that of the control group; the percentage of the survived flap area in the experimental group was higher than that in the control group [(87.6±3.2)% vs. (65.3±3.0)%, P<0.01]; the intraluminal diameter of the choke artery was greater in the experimental group than that in the control group[(49.3±3.1) μm vs. (35.1±2.3) μm, P<0.01]; and the relative expression of eNOS in the experimental group was higher than that in the control group (0.87±0.07 vs. 0.50±0.05, P<0.01). Conclusion:The distal vein (right posterior intercostal vein) of dorsal four-territory perforator flap of SD rats directly guided the pedicle artery blood supply to promote the expression of eNOS, dilated the arteries in each zone of the flap, increased the blood supply to the distal artery of the flap, and ultimately enhanced the flap survival area.

Objective:To explore the effect of distal veins on the survival of a dorsal four-territory perforator flap in rats.Methods:A total of 32 SD rats were randomly divided into the control group and the experimental group, with 16 rats in each group. The multi-territory perforator flap including the bilateral iliolumbar and bilateral posterior intercostal angiosomes was cut from the back of each rat, with the size of 6 cm×7 cm. The right iliolumbar artery and vein were preserved in the control group, while the right iliolumbar artery and the right posterior intercostal vein were preserved in the experimental group. In both groups, incisions were made between the right iliolumbar angiosome and the right posterior intercostal angiosome. Finally, the flap was sutured back to their orthotopic site. At 6 hours and 1, 3, 5, 7 days after surgery, the blood perfusion at the bilateral iliolumbar and the left posterior intercostal vascular territories were measured. On the seventh day after surgery, the percentage of the survived area of the flaps were evaluated, arteriography was performed to observe the dilation of arteries within the flap, the intraluminal diameter of the choke artery in the choke 2 area was measured using hematoxylin and eosin staining, and the relative expression of endothelial nitric oxide synthase (eNOS) was detected by Western blotting. SPSS 28.0 was used for statistical analysis, and measurement data were presented as Mean±SD. Independent sample t-test was used to compare data across two groups. P<0.05 was considered statistically significant. Results:(1) At 6 hours and 1, 3, 5, 7 days after surgery, the experimental group displayed higher blood perfusion than the control group at the bilateral iliolumbar and the left posterior intercostal vascular territories (all P<0.01). (2) On the 7th day after surgery, the artery dilation of the experimental group was more obvious than that of the control group; the percentage of the survived flap area in the experimental group was higher than that in the control group [(87.6±3.2)% vs. (65.3±3.0)%, P<0.01]; the intraluminal diameter of the choke artery was greater in the experimental group than that in the control group[(49.3±3.1) μm vs. (35.1±2.3) μm, P<0.01]; and the relative expression of eNOS in the experimental group was higher than that in the control group (0.87±0.07 vs. 0.50±0.05, P<0.01). Conclusion:The distal vein (right posterior intercostal vein) of dorsal four-territory perforator flap of SD rats directly guided the pedicle artery blood supply to promote the expression of eNOS, dilated the arteries in each zone of the flap, increased the blood supply to the distal artery of the flap, and ultimately enhanced the flap survival area.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Objective:To analyze the phenotype and genotype of two propositi with inherited hypodysfibrinogenaemia caused by compound heterozygous mutations, and investigate the molecular mechanism.Metheds:Two propositi and their family members(7 person in 3 generations and 10 person in 3 generations,respectively) were investigated. The activity of plasma fibrinogen (Fg:C) and thrombin time (TT) were analyzed by coagulation method, the antigen of plasma fibrinogen (Fg:Ag) was detected by immunoturbidimetry. All of the exons and flanking sequences of FGA,FGB,FGG of two propositi were amplified by PCR, followed by direct sequencing. The ClustalX-2, 1-win software was used to analyze the conservatism of mutated gene locus. PROVEAN and Mutation Taster were applied to analyze the pathogenicity of mutated amino acid. The changes of the protein spatial structure and intermolecular interaction were analyzed by Pymol.Results:Fg:C and Fg:Ag of proposita A and B were both significantly decreased (0.74 and 0.78 g/L, 0.96 and 0.94 g/L, respectively). Gene analysis revealed that proposita A and B both carried a heterozygous mutation c.2185G>A(p.AαGlu710Lys) in exon 6 of FGA. Furthermore, proposita A also carried a heterozygous mutation c.701G>T(p.γTrp208Leu) in exon 7 of FGG, and proposita B carried a heterozygous mutation c.1015A>C(p.γSer313Arg) in exon 8 of FGG. Phylogenetic analysis suggested that p.AαGlu710,p.γTrp208 and p.γSer313 were highly conserved among homologous species. All variants were predicted to be deleterious by two online bioinformatic softwares. The protein model analysis indicated that protein spatial structure and intermolecular hydrogen bonds were changed by these variants, which destroyed the stability of Fg.Conclusion:The compound heterozygous mutations of p.AαGlu710Lys and p.γTrp208Leu,p.AαGlu710Lys and p.γSer313Arg might account for the hypodysfibrinogenemia in two propositi.