[Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm].

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-ß in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

[Gilbert's syndrome: hyperbilirubinemia enemy or friend].

Gilbert's syndrome is a kind of benign inherited disease of bilirubin binding disorder, mainly due to the homozygous polymorphism A(TA)7TAA in the promoter of the gene for uridine diphosphate -glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter, designated as UGT1A1*28, with UGT activity reduction to 30% of the normal value. Therefore, circulating fat-soluble unconjugated bilirubin cannot be converted into water-soluble conjugated bilirubin, leading to unconjugated hyperbilirubinemia. Bilirubin has a strong affinity for erythrocyte phospholipids, which interferes with membrane composition and dynamics, resulting in increased erythrocytes fragility, easy rupture, and gradual shortening of survival time. However, there are no obvious sign of hemolysis or abnormal iron metabolism, erythrocytes and bone marrow morphology. A small amount of chronic hemolysis stimulates extramedullary (normal bone marrow morphology) hematopoiesis, ensuing compensatory increase in circulating erythrocytes and hemoglobin. Hyperbilirubinemia may also weaken gastrointestinal motility, increase passive diffusion and absorption across the intestinal mucosal epithelium by 1.5 to 2 times, thereby aggravating or worsening hyperbilirubinemia mainly with unconjugated bilirubin circulation, which indicates that there is a causal relationship between the circulating bilirubin concentration and rapid erythrocytes turnover and hemolysis rate in patients with Gilbert's syndrome. Interestingly, bilirubin also has significant antioxidant and anti-mutagenic activities, and the potential health benefits of mild hyperbilirubinemia in Gilbert's syndrome include reduced prevalence of cardiovascular disease, type 2 diabetes mellitus (and related risk factors), certain cancers, and cardiovascular-related and all-cause mortality. Exogenous bilirubin and biliverdin supplements in intestinal epithelial cells can be absorbed and may increase circulating concentration of these antioxidant compounds. With this information, we hope to raise awareness of the potentially harmful and beneficial effects of benign hyperbilirubinemia, and explore and develop beneficial medical interventions.

High expression of ACE2 in the human lung leads to the release of IL6 by suppressing cellular immunity: IL6 plays a key role in COVID-19.

OBJECTIVE: The pathogenesis of coronavirus disease 2019 (COVID-19) remains clear, and no effective treatment exists. SARS-CoV-2 is the virus that causes COVID-19 and uses ACE2 as a cell receptor to invade human cells. Therefore, ACE2 is a key factor to analyze the SARS-CoV-2 infection mechanism. MATERIALS AND METHODS: We included 9,783 sequencing results of different organs, analyzed the effects of different ACE2 expression patterns in organs and immune regulation. RESULTS: We found that ACE2 expression was significantly increased in the lungs and digestive tract. The cellular immunity of individuals with elevated ACE2 expression is activated, whereas humoral immunity is dampened, leading to the release of many inflammatory factors dominated by IL6. Furthermore, by studying the sequencing results of SARS-CoV-2-infected and uninfected cells, IL6 was found to be an indicator of a significant increase in the number of infected cells. However, although patients with high expression of ACE2 will release many inflammatory factors dominated by IL6, cellular immunity in the colorectum is significantly activated. This effect may explain why individuals with SARS-CoV-2 infection have severe lung symptoms and digestion issues, which are important causes of milder symptoms. CONCLUSIONS: This finding indicates that ACE2 and IL6 inhibitors have important value in COVID-19.

Investigations on the complex flows induced by dual-swept/dual-ramp wedges in supersonic flows.

The caret inlet with a dual-swept/dual-ramp configuration has excellent stealth performance and aerodynamic capability. Most previous investigations on this configuration have focused on experiments and numerical simulations but there are relatively few theoretical investigations. In this study, the flow field characteristics of dual-swept/dual-ramp configuration are investigated analytically and numerically. An analytical approach that combines the shock dynamics with a "spatial dimension reduction" was used to analyze the characteristics of the wave structures and state parameters of the flow field. The effects of the sweep angles and inflow Mach number on the flow field characteristics are investigated. The results indicate that the problem of shock/shock interaction in two intersecting wedges of large back-swept angle is a problem of weak shock interaction. Therefore, the theory of weak shock interaction is used to investigate the flow field characteristics, including the uniformity of the flow field and the total pressure recovery performance.

Up-regulation of long non-coding RNA SNHG1 contributes to proliferation and metastasis in laryngeal squamous cell carcinoma.

OBJECTIVE: To investigate the expression of human long non-coding ribonucleic acid (RNA) small nucleolar RNA host gene 1 (SNHG1) in laryngeal carcinoma tissues, and to study the effect of SNHG1 on biological functions of laryngeal carcinoma HEp-2 cells. PATIENTS AND METHODS: The expression levels of SNHG1 in 20 pairs of laryngeal carcinoma tissues and para-carcinoma tissues were detected via Real-time fluorescence quantitative polymerase chain reaction (PCR). Laryngeal carcinoma cells were transfected with small interfering (si)-SNHG1 transiently using the RNA interference technique. The effects of si-SNHG1 on proliferation, apoptosis, invasion, and migration of laryngeal carcinoma HEp-2 cells were detected via cell counting kit-8 (CCK-8), colony formation assay, flow cytometry, and wound healing and Transwell assay, respectively. RESULTS: Results of PCR showed that the expression of SNHG1 in carcinoma tissues was increased compared with that in para-carcinoma tissues. Results of CCK-8 and colony formation assay revealed that SNHG1 knockdown could significantly inhibit the proliferation of laryngeal carcinoma HEp-2 cells. Flow cytometry showed that transfection with si-SNHG1 could promote the apoptosis of HEp-2 cells. Moreover, results of wound healing and Transwell assay showed that SNHG1 knockdown could inhibit invasion and migration of HEp-2 cells through inhibiting the epithelial-mesenchymal transition (EMT) process and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in cells. CONCLUSIONS: The expression of SNHG1 in laryngeal carcinoma tissues is significantly higher than that in para-carcinoma tissue. Patients with high expression of SNHG1 have a poor prognosis. SNHG1 knockdown in HEp-2 cells can inhibit cell proliferation, invasion, and metastasis, and can promote apoptosis.

[Clinical value of endoscopicultrsaonography and multi-slice spiral CT in Siewert â ¡and â ¢ type adenocarcinoma of esophagogastric junction].

Objective: To investigate the clinical value of endoscopic ultrasonography (EUS) and Multi-slice Spiral CT (MSCT) in the preoperativestaging of tumor(T) and lymph node (N) metastasis in patients with SiewertⅡand Ⅲ typeadenocarcinoma of esophagogastric junction(AEG). Methods: Clinical data of 145 Siewert Ⅱ and Ⅲ type AEG patientswithout preoperative chemoradiotherapy were retrospectively reviewed. Theyall received preoperative EUS and MSCT examination and underwent surgical resection, and the results of EUS and MSCT were compared with their postoperative pathologic staging. Results: The sensitivity, specificity, and accuracy of EUS for T stage in Siewert Ⅱ and Ⅲ type AEG were higher than those of MSCT. The total accuracy of EUS and MSCT were 90.3% and 63.5%, respectively, and the difference was statistically significant (χ(2)=29.52, P<0.01). The sensitivity of EUS for T1, T2 and T3 were 89.5%, 91.1% and 85.2%, respectively, which were significantly higher than 42.1%, 66.7% and 29.6% of MSCT (χ(2)=9.47, P<0.01 for T1; χ(2)=8.07, P<0.01 for T2; χ(2)=17.40, P<0.01 for T3). In addition, the total accuracy of EUS and MSCT for lymph node metastasis status of Siewert Ⅱ and Ⅲ type AEG were 75.9% and 64.8%, respectively, showing a statistically significant difference(χ(2)=4.23, P=0.04). The sensitivity of EUS for N1 and N2 were 82.1% and 79.2%, respectively, which were significantly higher than 53.6% and 60.4% of MSCT (χ(2)=5.24, P=0.02; χ(2)=4.48, P=0.03). There was no statistical significance for sensitivity of EUS and MSCT in N0 and N3 (P>0.05). Conclusion: EUS diagnosis of T and N staging in Siewert Ⅱ/Ⅲ type AEG showed significantly greater performance than MSCT.

Morbidity and Safety of Iliac Crest Reference Array Pins in Navigated Total Hip Arthroplasty: A Prospective Cohort Study.

BACKGROUND: Navigated total hip arthroplasty (THA) can employ intra-osseous pins through a separate incision to secure reference arrays to the iliac crest. This study is the first to investigate the consequences of pin use in THA in vivo. METHODS: A prospective, consecutive series of 43 patients presenting for navigated THA were included. Two temporary 125 × 4 mm Schanz screws were inserted into the iliac crest for the attachment of a reference array. Telephone follow-up occurred at 6 and 12 weeks post-operatively. Patients were asked about pain, interference with daily activities, how often the wound was noticed, and duration of discomfort. Patient body mass index was recorded. RESULTS: The follow-up rate was 100%. Pin site pain at any time post-operatively was reported by 24 patients (56%). This improved to 30%, 9%, and 2% at 3, 6, and 12 weeks, respectively. On average, pain lasted for 16 days total. The most common complaints after pain were clothing discomfort (23%), pain when wearing a belt (12%), or pain when mobilizing (9%). For the majority (98%) of patients, all symptoms had resolved by 12 weeks. There was no nerve injury, pin site fracture, infection, or screw breakage. Patients with body mass index greater than 30 kg/m2 were up to 3 times more likely to experience pin site pain (P = .05), and had a longer duration of pain (P = .04). CONCLUSION: Surgeons and patients should be aware that using navigational pins for array fixation carries low complication rates but often will cause pain and irritation that resolves in the short term.

Glaucoma surgery and induced astigmatism: a systematic review.

BACKGROUND: The refractive outcomes of glaucoma surgeries, particularly their effect on astigmatism, are incompletely understood. MAIN BODY: Trabeculectomy is associated with a considerable amount of with-the-rule astigmatic change in the immediate postoperative period. This is followed by a gradual against-the-rule shift. These changes are altered with the use of mitomycin C (MMC). Non-penetrating surgery such as deep sclerectomy is also associated with a similar or smaller degree of induced astigmatism. Minimally invasive glaucoma surgery appears to be astigmatically neutral. There is no clear evidence regarding refractive outcomes of glaucoma drainage device surgery. CONCLUSIONS: Induced astigmatism may account for a reduction in unaided visual acuity in the early postoperative period following a successful trabeculectomy. These changes appear to stabilise at 3 months, and it would be prudent to defer the prescription of new glasses until this time. If sequential cataract surgery is to be performed, toric intraocular lenses can be a useful option for astigmatic correction.

[The effects and mechanisms of berberine on proliferation of papillary thyroid cancer K1 cells induced by high glucose].

Objective: To study the effect and mechanisms of berberine (BBR) on the proliferation of papillary thyroid cancer K1 cells induced by high glucose. Methods: K1 cells were cultured under 5.5 mmol/L or 25 mmol/L glucose condition with or without different concentration of BBR (0, 10, 40 and 80 µmol/L) for 24 hours. The proliferations of K1 cells in each condition were detected by MTT. Western blot was used to measure the expression of nuclear factor erythroid 2-related factor 2(Nrf2), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated-Akt (p-Akt). The distribution pattern of Nrf2 in K1 cells was determined using immunofluorescent staining. Results: Compared with 5.5 mmol/L condition, the proliferation rate [(126.64±5.41) % vs (87.31±3.67)%], expression levels of PI3K (0.425±0.019 vs 0.272±0.039), p-Akt/Akt (0.446±0.021 vs 0.168±0.035) and Nrf2 (0.597±0.014 vs 0.308±0.026), and Nrf2 distribution (93.0% vs 23.1%) in nuclear of K 1 cells under 25 mmol/L condition were significantly elevated, respectively (all P<0.01). Addition of BBR in 25 mmol/L condition dose dependently (10, 40, 80 µmol/L) lowered the proliferation rate of K1 cells [(111.76±4.10)%, (70.03±2.18)%, (32.41±3.76)% vs (126.64±5.41)%, all P<0.05], and suppressed the expression of PI3K, p-Akt/Akt, Nrf2, and Nrf2 nuclear distribution (P<0.05). Conclusions: BBR dose dependently inhibited the proliferation of high glucose-induced K1 cells. This effect was associated with the suppression on of PI3K/Akt signaling activation, Nrf2 expression and its nuclear translocation.

Autologous hematopoietic stem cell transplantation in patients with end-stage liver disease: a 5-year follow-up study of 48 patients.

OBJECTIVE: To investigate the long-term therapeutic effect of autologous hematopoietic stem cell transplantation in patients with End-stage Liver Disease (ESLD). PATIENTS AND METHODS: Forty-eight ESLD patients underwent autologous CD34+ stem cell transplantation were retrospectively reviewed. Changes in clinical and biochemical data, complications, and quality of life were monitored at 3, 6, 12, 36, and 60 months following the stem cell transplantation. Liver biopsies were obtained for histopathological analysis using Ishak system. RESULTS: Marked improvement in clinical and biochemical data was observed during the long-term follow-up. Serum albumin was significantly increased (p<0.001), while total serum bilirubin, prothrombin time (PT), and international normalized ratio (INR) were all significantly decreased (p<0.001). Ishak inflammation and fibrosis scores were significantly decreased with the increased time (p<0.001). The number of patients with ascites, model of end-stage liver disease (MELD) score, Child-Pugh class, and indocyanine green (ICG) score were all markedly reduced with increased time. Meanwhile, the quality of life score of the patients was significantly increased (p<0.001). Six patients died during the 5-years follow-up, and complications occurred in 17 patients. The incidence of complications was significantly associated with mortality of the patients (p<0.05). CONCLUSIONS: The study provided the evidence that autologous CD34+ stem cell transplantation could offer a long-term therapeutic benefit to patients with ESLD. The complications occurred during the process was significantly associated with survival of the patients. Future studies on a large cohort of patients are needed to confirm the long-term effect of stem cell therapy on ESLD.

MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition.

OBJECTIVE: Down-regulation of miR-138 is observed in a variety of cancers, which suggests that miR-138 may be involved in cancer pathogenesis. Our current work aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human NSCLC cells. MATERIALS AND METHODS: Cell proliferation was determined by MTT assay. Real-time PCR and western blot were performed to detect the mRNA and protein expression levels. The target of miR-138 was validated by luciferase activity assay. RESULTS: Compared with the chemosensitive parental cells, miR-138 was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition, the epithelial-mesenchymal transition (EMT) related markers E-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2 (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that ZEB2 was a direct target of miR-138. CONCLUSIONS: Our study demonstrates that miR-138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a potential therapeutic target for drug-resistant NSCLC patients.

An acute intraocular pressure challenge to assess retinal ganglion cell injury and recovery in the mouse.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma.

Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs.

OBJECTIVE: The main objective of this study was to investigate, in a population of normal postmenopausal women, the association between menopause and severity of lumbar disc degeneration from the first lumbar to the first sacral vertebra on magnetic resonance imaging. METHODS: Between January 2010 and May 2013, 846 normal women and 4230 intervertebral discs were retrospectively analyzed. Age, height, weight and years since menopause (YSM) were recorded. Disc degeneration was evaluated using the modified Pfirrmann grading system. RESULTS: Compared to premenopausal and perimenopausal women, postmenopausal women had more severe disc degeneration after removal of age, height and weight effects (p < 0.0001). Postmenopausal women were divided into six subgroups for every 5 YSM. When YSM was below 15 years, there was a significant difference between every two groups, i.e. groups 1-5 YSM, 6-10 YSM and 11-15 YSM (p < 0.01). A positive trend was observed between YSM and severity of disc degeneration, respectively, i.e. L1/L2 (r = 0.235), L2/L3 (r = 0.161), L3/L4 (r = 0.173), L4/L5 (r = 0.146), L5/S1 (r = 0.137) and all lumbar discs (r = 0.259) (p < 0.05 or 0.01). However, when YSM was above 15, there was no difference, i.e. groups 16-20 YSM, 21-25 YSM and 26-30 YSM (p > 0.05), and the significance correlation also disappeared (p > 0.05). CONCLUSION: Menopause is associated with disc degeneration in the lumbar spine. The association almost entirely occurred in the first 15 years since menopause, suggesting estrogen decrease may be a risk factor for lumbar disc degeneration.

Glaucomatous optic neuropathy evaluation project: factors associated with underestimation of glaucoma likelihood.

IMPORTANCE: Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire. OBJECTIVES: To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010. INTERVENTIONS: A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood. MAIN OUTCOMES AND MEASURES: Agreement (κ and weighted κ) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood. RESULTS: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1% (1.6%) and 23.8% (1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0% (1.2%) and 8.9% (1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs. CONCLUSIONS AND RELEVANCE: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2.

Serum uric acid is associated with arterial stiffness in men with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Increased serum uric acid levels and vascular atherosclerosis are very common in diabetes. However, few studies focused on the relationship between serum uric acid and aortic or peripheral arterial stiffness in newly diagnosed diabetic patients. This study investigated the association between serum uric acid levels and carotid-femoral pulse wave velocity (cfPWV) or carotid-radial (cr) PWV in male patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: 106 male patients with newly diagnosed T2DM were recruited. cfPWV and crPWV as well as anthropometric parameters, blood pressure, serum uric acid, blood glucose, fasting insulin, C-reactive protein and blood lipids were measured. RESULTS: The subjects were divided into low uric acid (UA) subgroup and high UA subgroup according to uric acid median. cfPWV and crPWV were significantly higher in high UA subgroup. Serum uric acid significantly correlated with cfPWV (r = 0.533, P < 0.001), crPWV (r = 0.334, P = 0.001), waist circumference (r = 0.350, P < 0.001), waist-to-hip ratio (r = 0.254, P = 0.009), fasting insulin (r = 0.432, P < 0.001), HOMA-IR (r = 0.173, P = 0.042), fasting blood glucose (r = -0.271, P = 0.005), haemoglobin A1c (r = -0.202, P = 0.038), and HDL-cholesterol (r = -0.267, P = 0.006) after correction for age. Stepwise multiple regressions showed that the independent determinants of cfPWV were serum uric acid, age, C-reactive protein, HDL-cholesterol, and smoking status. And the independent determinants of crPWV were serum uric acid, age, diastolic blood pressure, and HDL-cholesterol. CONCLUSIONS: Serum uric acid is significantly associated with increased aortic and peripheral arterial stiffness in men with T2DM at the early stage.

Relationship between autoantibody to the angiotensin II-1 receptor and cardiovascular manifestations of Graves' disease.

OBJECTIVE: To investigate the role of autoantibody against angiotensin II-1 receptor (AT1-AA) in patients with cardiovascular manifestations of Graves' disease (GD). METHODS: The epitope of the second extracellular loop of AT1 receptor (165-191) was synthesized and used as antigens to screen the autoantibody by enzyme linked immunosorbent assay (ELISA). The patients with GD were divided into the patients with cardiovascular manifestations associated to GD (Group A, n=58) and the patients with GD not complicated by heart disease (Group B, n=60). 40 healthy subjects were included in the study (Group C, n=40). Echocardiography was performed and the differences of echocardiography parameters were compared between AT1-AA positive and negative groups in group A. Factors related to left heart enlargement were analyzed by multiple logistic regression. RESULTS: (1) The frequency of AT1-AA in Group A (52.2%, 32/58) were significantly higher than those in Group B (16.7%, 10/60) and Group C (12.5%, 5/40) (all p<0.001). (2) There were no differences in the level of TGAb, TPOAb and TRAb between AT1-AA positive and negative groups in patients with GD (all p>0.05). (3) In patients with cardiovascular manifestations of GD, the ratios between left atrial and ventricular enlargement (LAE and LVE) were significantly higher in the AT1-AA positive group than in the AT1-AA negative group (68.8% vs. 26.9%, 62.5% vs. 23.1%, all p<0.01); the frequency of atrial fibrillation differed significantly between these 2 groups (53.1% vs. 19.2%, p<0.01). (4) Regression analysis demonstrated that the positive AT1-AA and course of GD were significantly correlated to the presence of LAE and LVE. CONCLUSIONS: AT1-AA plays an important role in the pathogenesis of cardiovascular manifestations associated to GD. Especially, AT1-AA is involved in left cardiac dilatation of GD complicated by heart disease, which represents a cardio-vascular risk factor for GD patients.