The -250G/A and -514C/T Polymorphisms in Hepatic Lipase Gene Promoter Confers an Increased Risk of Hepatocellular Carcinoma in a Chinese Population.

INTRODUCTION AND AIM: Hepatocellular carcinoma (HCC) is a lethal malignancy, but the molecular mechanisms of hepatocarcinogenesis remain undefined. The present study aims to investigate the relationship between polymorphisms of the hepatic lipase (HL) gene promoters and risk of HCC. MATERIAL AND METHODS: Totally, 279 HCC patients and 200 healthy individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) was used to analyze the genotypes of HL gene. Logistic regression analysis was conducted to identify risk factors of HCC. RESULTS: There was significant difference in the distribution of smoking history, drinking history, and family history of subjects between the case and control groups (all p < 0.05). Difference in the -250G/A (p = 0.011; OR = 1.61; 95%CI: 1.11-2.34) and -514C/T (p = 0.007; OR = 1.65; 95%CI: 1.14-2.38) genotypes and allele frequencies between two groups was significant. A higher risk of HCC was identified in those with polymorphisms in the - 250G/A (p = 0.007; OR = 1.45; 95%CI: 1.11-1.89) and -514C/T (p = 0.003; OR = 1.51; 95%CI: 1.15-2.00). Polymorphisms at - 250G/A (GA + AA) (p = 0.025; OR = 1.55; 95%CI: 1.06-2.28), -514C/T (CT + TT) (p = 0.021; OR = 1.57; 95%CI: 1.07-2.29), smoking history (p = 0.017; OR = 1.70; 95%CI: 1.10-2.63) and drinking history (p = 0.003; OR = 2.04; 95%CI: 1.27-3.27) were significantly related to the risk of HCC (all p < 0.05). CONCLUSION: The results obtained from this study indicated that polymorphisms of -250G/A and -514C/T in HL gene promoters were associated with the risk of HCC.

Immune response- and viral control-related pathways in the progression of chronic hepatitis B.

BACKGROUND: Chronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases. OBJECTIVE: This study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction. METHODS: In this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway. RESULTS: We constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state. CONCLUSIONS: By pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.

[Comparison of clinical effects of different irrigant solutions combined with different agitation techniques in the treatment of chronic apical periodontitis with fistula].

PURPOSE: To evaluate the effect of combination of auxiliary irrigation technology and root canal irrigation solution in the treatment of chronic apical periodontitis with fistula, and try to seek a more effective and minimally invasive therapeutic strategy. METHODS: One hundred and fifty patients with fistulous chronic apical periodontitis who were diagnosed in Hefei Stomatological Hospital from January 2021 to January 2022 were randomly divided into 6 groups, 25 cases in each group. The 6 groups were as follows, group A: 0.5%NaOCl +ultrasonically activated irrigation; Group B: 1.0%NaOCl+ultrasonically activated irrigation; Group C: 2.0%CHX+ultrasonically activated irrigation; Group D: 0.5%NaOCl+sonic activation; Group E: 1.0%NaOCl+sonic activation; Group F: 2.0%CHX+sonic activation. The fistula healing time, treatment effect and postoperative pain were observed in each group. The data were analyzed with SPSS 20.0 software package. RESULTS: In terms of fistula healing, the 10-day fistula healing rate of group E and group F was higher than that of group A and group D，and the difference was statistically significant(P＜0.05); but there was no significant difference between group E and group F (P＞0.05). The effective rate at 1 month after operation in group A was lower, and the difference was significant (P＜0.05). In terms of postoperative pain, the VAS score of group A was lower than that of group E and group F at all time points, and the difference was statistically significant(P＜0.05). CONCLUSIONS: In the treatment of chronic apical periodontitis with fistula, 1.0% NaOCl or 2.0% CHX combined with ultrasonically activated irrigation or sonic activation obtain a better short-term effect，of which the sonic activation group can also obtain early healing of the fistula, but the incidence of postoperative pain is higher when sonic activation is used.

Efficacy of Shenmai injection for the treatment of chronic heart failure: A protocol of systematic review.

BACKGROUND: This study will assess the efficacy and safety of Shenmai injection (SMI) for the treatment of chronic heart failure (CHF). METHODS: The following electronic bibliographic databases will be searched from inception to the March 25, 2020 without language and publication time limitations: MEDLINE, PUBMED, Cochrane Library, Web of Science, Scopus, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All randomized controlled trials related to the SMI for patients with CHF will be included. All study selection, data extraction, and study quality will be carried out by 2 reviewers. Any disagreements will be solved by a third reviewer through discussion. RevMan 5.3 software will be used for data synthesis and data analysis. RESULTS: This study will summarize the present evidence of SMI for the treatment of patients with CHF. CONCLUSION: The findings of this study will determine whether SMI is effective and safety for the treatment of CHF or not. STUDY REGISTRATION NUMBER: INPLASY202050029.

Acute esophageal obstruction caused by reverse migration of gastric bezoars: A case report.

BACKGROUND: Bezoars can be found anywhere in the gastrointestinal tract. Esophageal bezoars are rare. Esophageal bezoars are classified as either primary or secondary. It is rarely reported that secondary esophageal bezoars caused by reverse migration from the stomach lead to acute esophageal obstruction. Guidelines recommend urgent upper endoscopy (within 24 h) for these impactions without complete esophageal obstruction and emergency endoscopy (within 6 h) for those with complete esophageal obstruction. Gastroscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. CASE SUMMARY: A 59-year-old man was hospitalized due to nausea, vomiting and diarrhea for 2 d and sudden retrosternal pain and dysphagia for 10 h. He had a history of type 2 diabetes mellitus for 9 years. Computed tomography revealed dilated lower esophagus, thickening of the esophageal wall, a mass-like lesion with a flocculent high-density shadow and gas bubbles in the esophageal lumen. On gastroscopy, immovable brown bezoars were found in the lower esophagus, which led to esophageal obstruction. Endoscopic fragmentation was successful, and there were no complications. The symptoms of retrosternal pain and dysphagia disappeared after treatment. Mucosal superficial ulcers were observed in the lower esophagus. Multiple biopsy specimens from the lower esophagus revealed nonspecific findings. The patient remained asymptomatic, and follow-up gastroscopy 1 wk after endoscopic fragmentation showed no evidence of bezoars in the esophagus or the stomach. CONCLUSION: Acute esophageal obstruction caused by bezoars reversed migration from the stomach is rare. Endoscopic fragmentation is safe, effective and minimally invasive and should be considered as the first-line therapeutic modality.

Effect of Xingnaojing injection for the treatment of acute alcoholism: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will assess the effect of Xingnaojing injection (XNJI) for the treatment of acute alcoholism (AAH). METHODS: The bibliographic literature sources will be systematically searched in MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure Database, Wan fang Database, and VIP Science Technology Periodical Database. All above electronic databases will be sought from inception to the April 1, 2020. We will not apply any limitations to language and publication time. In addition, we will also search other literature sources. Two reviewers will carry out study selection, data extraction, and methodological quality evaluation, respectively. Any divergences will be resolved by a third reviewer through discussion. We will use RevMan 5.3 software to analyze data analysis. RESULTS: This study will summarize present evidence to assess the effect of XNJI for the treatment of AAH. CONCLUSION: This study will investigate whether XNJI is effective and safety for AAH. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040197.

[Epidemiological study on status of Helicobacter pylori in children and teenagers in Wuwei city, Gansu province].

OBJECTIVE: To investigate the prevalence of Helicobacter pylori (Hp) infection among children aged 3 to 18 years old of Wuwei city, Gansu province. METHODS: The study was based upon a personal questionnaire and a determination of Hp antigen using the Hp stool antigen test (HpSA) method. A total of 938 subjects and 96 families were selected in Wuwei city. Eighty children and teenagers with a definite positive Hp stool antigen test were examined by serum Western blotting method. RESULTS: The prevalence of Hp was 72.3% (678/938) with no age difference. Prevalence of Hp infection was correlated with type of dwelling, occupation of parents, drinking water source, kindergarten attendance, consumption of raw vegetables, a poor oral hygiene and breast feeding etc. According to the multivariate analysis, drinking water source, kindergarten attendance and consumption of raw vegetables were most strongly associated with prevalence of Hp in children and adolescents. The infection rate of parents whose children were infected with Hp was higher than that of those whose children were not infected [82.3% (121/147) vs 47.4% (18/38), chi(2) = 19.736, P < 0.05]. The antibody responses of 57 samples (71.3%) from 80 children were of type I Hp and 23 samples (28.7%) type II. CONCLUSIONS: Hp infective rate is high in Wuwei city. The data support maternal-child and sibling-sibling transmission as the primary transmission routes of Hp. The results of serological analysis confirm that the majority of Wuwei Hp infection is of type I.

[Expression of cyclooxygenase-2 and urokinase plasminogen activator in gastric carcinoma and the clinical significance thereof].

OBJECTIVE: To investigate expression of cyclooxygenase-2 (COX-2) and urokinase plasminogen activator (uPA) in gastric carcinoma and the clinical significance thereof. METHODS: Strepavidin-peroxidase method was used to detect the expression of COX-2 and uPA in 192 specimens of gastric carcinoma, 56 specimens of paracancer tissues obtained during operation. Immunohistochemical double staining was used to detect the microvessel density (MVD) and microlymphatic density (MLD). Thirty specimens of normal gastric mucosa obtained during gastroscopy were used as controls. RESULTS: The positive rates of COX-2 in the gastric carcinoma and paracancer tissues were 67.7% and 62.5% respectively, both significantly higher than that of the control group (40.0%, both P < 0.05). The positive expression of COX-2 in gastric carcinoma was significantly related with the depth of invasion and MVD (both P < 0.05). The positive rates of uPA in the gastric carcinoma, paracancer tissue were 78.1% and 44.6% respectively, both significantly higher than that of the control tissues (6.7%, both P < 0.01) and there was a significant difference in the positive rates of uPA between the first 2 groups too (P < 0.01). The positive expression of uPA in gastric carcinoma was significantly related with lymph node metastasis, depth of invasion, Lauren typing, differentiation, MVD, and MLD (P < 0.05, P < 0.01). COX-2 expression was positively linked with uPA expression (r = 0.167, P = 0.021). The survival time of the uPA positive group was (38 +/- 4) months, significantly shorter than that of the negative group [(54 +/- 6) months, P < 0.05]. The survival time of the group positive in both COX-2 and uPA was (27 +/- 3) months, significantly shorter than that of the single positive or double negative groups [both (58 +/- 4) months, both P < 0.01). CONCLUSION: COX-2 and uPA are highly expressed in gastric carcinoma. COX-2 expression is positively linked with uPA expression. COX-2 and uPA in the gastric carcinoma participate in the development of gastric cancer in the early process. uPA is significantly related with the survival time.

[Expression and Significance of PD-L1, HSP90 and HSP90α in Serum of Patients with Acute Leukemia].

OBJECTIVE: To explore the expression and clinical significance of PD-L1, heat shock protein 90 (HSP90) and HSP90α in the serum of patients with acute leukemia (AL) of different types and disease stages. METHODS: A total of 84 AL patients from January 2013 to October 2016 in our hospital and 20 healthy persons as controls were selected. All the samples of serum or bone marrow were separated. The protein expression levels of serum HSP90, HSP90α were detected by ELISA. The flow cytometry was used to detect PD-L1 expression. The relationship of the expression level of PD-L1, HSP 90, and HSP90α with clinical outcome was analyzed. RESULTS: The expression levels of serum HSP90, HSP90α and PD-L1 positive rate in AL patients were significantly higher those that in control group (P<0.05), the expression levels of serum HSP90, HSP90α and PD-L1 positive rate of Al patients in remission were lower than those in newly diagnosed patients (P<0.05). The expression level of HSP90, HSP90α and PD-L1 positive rate in the relapsed AL patients were higher than those in newly diagnosed AL patients and patients in remission (P<0.05). There was no significant difference of HSP90 protein level and PD-L1 positive rate between newly diagnosed AML patients and ALL patients(P>0.05). HSP90α level of newly diagnosed AML patients was lower than that in newly diagnosed ALL (P<0.05). HSP90α and HSP90 levels and PD-L1 positive rate in no remission patients were significantly higher than those in complete remission patients (P<0.05). The HSP90α level in patients without recurrence decreased during chemotherapy. The HSP90α protein level was the lowest after the hematopoietic stem cell transplantation, but increased after relapse. CONCLUSION: The PD-L1,HSP90 and HSP90α play an important role in the developmental process of acute leukemia, which can be used as reference indications to assess clinical efficacy and prognosis.

[The effect of a combined nanoparticulate/calcium hydroxide medication on the biofilm of Enterococcus faecalis in starvation phase].

PURPOSE: To evaluate the efficacy of Ca(OH)2 with a silver nanoparticle suspension to eliminate the biofilm of Enterococcus faecalis (E. faecalis) in starvation phase. METHODS: The biofilm models of E．faecalis in the starvation phase were built in vitro with 256 extracted human single-rooted teeth, and the methods of plate culture count and crystal violet biofilm assay were applied to determine the effect of the inhibition of different intracanal medicament (silver nanoparticle with calcium hydroxide, silver nanoparticle alone, calcium hydroxide alone ) to the biofilm of E. faecalis in starvation phase at 1 and 7 days. The negative control group was treated with sterile water only. Statistical analysis was carried out with SPSS 13.0 software package. RESULTS: The inhibitory effect of Ca（OH）2+nanosilver on the biofilms of E. faecalis was found more significant than that of silver nanoparticle alone and calcium hydroxide alone at 1 and 7 days, and silver nanoparticle alone was more effective than calcium hydroxide alone. No difference in antimicrobial properties was observed between the two time points in the Ca(OH)2+silver nanoparticle group and silver nanoparticle group, while higher antimicrobial efficacy was observed in the Ca(OH)2 group after 7 days than 1 day. CONCLUSIONS: Silver nanoparticle with calcium hydroxide has an obvious inhibitory effect on the biofilm of E.faecalis in the starvation phase.

Role of osteopontin in the regulation of human bladder cancer proliferation and migration in T24 cells.

Osteopontin (OPN), a secreted acid glycoprotein with a variety of functions, promotes tumor proliferation, differentiation, invasion and metastasis. The aim of the current study was to investigate whether OPN may serve as a potential therapeutic target for human bladder cancer. RNA interference (RNAi) was performed to downregulate the expression of the OPN gene in T24 human bladder cancer cells. The mRNA and protein expression levels of OPN following RNAi were determined using reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the cell cycle progression, apoptosis and proliferation were investigated using by flow cytometric analysis and MTT assay. The cell invasion ability was measured using a Matrigel transwell assay. The mRNA and protein expression levels of OPN were found to be significantly downregulated following RNAi. The proliferation and invasion of T24 cells were significantly inhibited in vitro. In conclusion, RNAi­targeting OPN may inhibit the proliferation, invasion and tumorigenicity of human bladder cancer cells. Therefore, OPN may serve as a potential therapeutic target for human bladder cancer.

Lipopolysaccharide (LPS) induces the apoptosis and inhibits osteoblast differentiation through JNK pathway in MC3T3-E1 cells.

Bone degradation is a serious complication of chronic inflammatory diseases such as septic arthritis, osteomyelitis, and infected orthopedic implant failure. Up to date, effective therapeutic treatments for bacteria-caused bone destruction are limited. In our previous study, we found that LPS promoted osteoclast differentiation and activity through activation of mitogen-activated protein kinases (MAPKs) pathway such as c-Jun N-terminal kinases (JNK) and extracellular signal regulated kinase (ERK1/2). The current study was to evaluate the mechanism of LPS on the apoptosis and osteoblast differentiation in MC3T3-E1 cells. MC3T3-E1 osteoblasts were non-treated, treated with LPS. After treatment, the cell viability, the activity of alkaline phosphatase (ALP) and caspase-3 were measured. The expressions of osteoblast-specific genes and Bax, Bcl-2, and caspase-3 were determined by real-time quantitative polymerase chain reaction (qPCR). Protein levels of Bax, Bcl-2, caspase-3, and phosphorylation of MAPKs were measured using Western blotting assays. The MAPK signaling pathway was blocked by pretreatment with JNK inhibitor SP600125. LPS treatment induced a significant decrease in cell metabolism, viability, and ALP activity in MC3T3-E1 cells. LPS also significantly decreased mRNA expressions of osteoblast-related genes in MC3T3-E1 cells. On the other hand, LPS significantly upregulated mRNA expressions and protein levels of Bax and caspase-3 as well as activation of caspase-3, whereas decreased Bcl-2 expression in MC3T3-E1 cells. Furthermore, LPS significantly promoted MAPK pathway including the phosphorylation of JNK and the phosphorylation of ERK1/2; moreover, pretreatment with JNK inhibitor not only attenuated both of phosphorylation-JNK and ERK1/2 enhanced by LPS in MC3T3-E1 cells, but also reversed the downregulated expressions of osteoblast-specific genes including ALP and BSP induced by LPS. In conclusion, LPS could induce osteoblast apoptosis and inhibit osteoblast differentiation via activation of JNK pathway.

The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

OBJECTIVE: To evaluate the efficacy of imatinib administration before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). METHOD: Patients with imatinib therapy time exceeding 30 days pre-/post-transplant were screened in our data. Imatinib was used in induced or consolidated chemotherapy pre-transplant, or maintenance therapy after 60 days post-transplant (therapy time was less than 180 days) regardless of the molecular status of the disease. RESULTS: Sixty-nine patients with Ph+ ALL were enrolled in the retrospective analysis. Forty-four patients received imatinib therapy, including 24 pre-transplant, 9 post-transplant, and 11 both pre- and post-transplant. With a median follow-up time of 395 days (range, 55-2762 days) post-transplant, 3-year estimated overall survival was 62.3 ± 16.6, 40.0 ± 21.9, 41.7 ± 22.2, and 25.9 ± 11.4%, respectively (P = 0.221), and disease-free survival (DFS) was 53.6 ± 17.9, 20.0 ± 17.9, 33.3 ± 25.5% and 23.6 ± 11.4%, respectively (P = 0.421), in patients with imatinib therapy pre-transplant, post-transplant, both pre- and post-transplant, neither pre- nor post-transplant. The incidence of relapse at 3 year for patients with imatinib therapy post-transplant (n = 20) was 63.6%, comparing with 24.2% (P = 0.018) in patients without imatinib therapy post-transplant (n = 49). The ratio of CD4+CD25+Foxp3+ cells in blood was significantly higher at 30 and 60 days after imatinib therapy than that at the time of pre-imatinib in 20 patients (P = 0.019 and 0.001, respectively). CONCLUSIONS: Application of imatinib pre-transplant might have benefited for patients with Ph+ ALL. Whether administration of imatinib, regardless of the molecular status of the disease post-transplant increases relapse, is a worthy goal for further study.

[Shaping ability of two nickel-titanium rotary systems in simulated S-shaped canals].

OBJECTIVE: To evaluate the shaping ability of two nickel-titanium rotary systems (ProTaper and Hero642) in simulated S-shaped canals. METHODS: Thirty simulated S-shaped canals were randomly divided into three groups and prepared by ProTaper, Hero642, ProTaper combined with Hero642 respectively. All the canals were scanned before and after instrumentation, and the amount of material removed in the inner and outer wall and the canal width after instrumentation were measured with a computer image analysis program. RESULTS: There was significant difference in the amount of material removed at the inner side of apical curvature and outer side of apex between ProTaper combined with Hero642 and ProTaper files (P < 0.05) at the same tip size. The inner and outer wall of the canals were evenly prepared by ProTaper combined with Hero642, and the taper of canals were better than those prepared by Hero642. CONCLUSIONS: ProTaper combined with Hero 642 had better shaping ability to maintain the original shape and could create good taper canals in the simulated S-shaped canal model.

[Genotypes of hepatitis B virus in Henan Luohe area].

OBJECTIVE: To determine the main genotype of hepatitis B virus (HBV) prevailed in Henan Luohe area. METHODS: Serum specimens were collected from 94 HBsAg positive individuals, and HBV S gene were obtained by PCR amplifying, and the gene sequences were analyzed and the polygenetic tree was drawn by the software MEGA3. RESULTS: About 75.7% samples of HBV S gene clustered in genotype C, about 20% samples clustered at genotype B in the HBV polygenetic tree, about 4.3% samples clustered at genotype D in the HBV polygenetic tree. CONCLUSION: The main genotype of hepatitis B virus prevalent in Henan Luohe is genotype C, genotype B is rarely seen, and genotype D is rarely seen.

[Evaluation of the use of dental operating microscope in the management of blocked canals].

PURPOSE: This study was performed to evaluate the value of dental operating microscope(DOM) in treating blocked canals. METHODS: 161 blocked canals in 113 teeth were treated with ultrasonic instruments under DOM. The etiology of canal blockage included calcification, resinifying therapy and broken instruments. All canals were grouped based on the cause of blockage, teeth site and blockage location in canals, and then the success rates of negotiating ,using SPSS10.0 software package, were analyzed with X(2) test. RESULTS: The results showed that 131 canals were negotiated with a success rate of 81.37%.Blocked canals caused by calcification, resinifying therapy and broken instruments were managed with the success rate of 84.27%, 81.58% and 73.53%, respectively.There were no significant differences in the success rate(P>0.05). Blocked canals of anterior were managed successfully with a success rate of 93.48%,canals of premolar with a success rate of 84.61%,and canals of molar with a success rate of 72.37%. There were significant differences in the success rate between anterior and molar teeth(P<0.01).When the blockage was located in straight canals or above the root canal curvature,canals were negotiated with a success rate of 93.98>.However,the success rate decreased to 21.42> when the blockage located below the root canal curvature,and significant differences were found(P<0.01). CONCLUSIONS: It is an effective way to use dental operating microscope to treat blocked canals, but the therapeutic effects might be affected by sites of the teeth and the blockage location in canals.

[A novel mutation in antithrombin gene results in hereditary antithrombin deficiency].

OBJECTIVE: To investigate the antithrombin (AT) activity (AT: A) and AT antigen (AT: Ag) level in a Chinese family with type I antithrombin (AT) deficiency, and to explore the molecular mechanism of AT deficiency. METHODS: Immuno-nephelometry and chromogenic assay were used to detect the plasma level of AT: A and AT: Ag, respectively. Genomic DNA was isolated from the peripheral blood, and all the seven exons and exon-intron boundaries of AT gene were amplified by PCR and direct sequencing. RESULTS: The plasma levels of AT: A and AT: Ag of the proband were 45% and 97 mg/L, respectively, which led to a type I AT deficiency. A heterozygous T to A mutation was found at nucleotide 9833 in exon 5 resulting in a Tyr363Stop nonsense mutation. The sequencing results from the pedigree indicated that four other members also had this mutation. CONCLUSION: This heterozygous nonsense mutation of T9833A in exon 5 resulting in venous thrombosis is a novel genetic defect of hereditary AT deficiency, which has not been described before.